Skip to main content
Top

Open Access 17-06-2024 | Human Immunodeficiency Virus

Suppression of HIV-TAT and cocaine-induced neurotoxicity and inflammation by cell penetrable itaconate esters

Authors: B. Celia Cui, Marina Aksenova, Aliaksandra Sikirzhytskaya, Diana Odhiambo, Elizaveta Korunova, Vitali Sikirzhytski, Hao Ji, Diego Altomare, Eugenia Broude, Norma Frizzell, Rosemarie Booze, Michael D. Wyatt, Michael Shtutman

Published in: Journal of NeuroVirology

Login to get access

Abstract

HIV-associated neurological disorder (HAND) is a serious complication of HIV infection marked by neurotoxicity induced by viral proteins like Tat. Substance abuse exacerbates neurocognitive impairment in people living with HIV. There is an urgent need for therapeutic strategies to combat HAND comorbid with Cocaine Use Disorder (CUD). Our analysis of HIV and cocaine-induced transcriptomes in primary cortical cultures revealed significant overexpression of the macrophage-specific gene aconitate decarboxylase 1 (Acod1). The ACOD1 protein converts the tricarboxylic acid intermediate cis-aconitate into itaconate during the activation of inflammation. Itaconate then facilitates cytokine production and activates anti-inflammatory transcription factors, shielding macrophages from infection-induced cell death. However, the immunometabolic function of itaconate was unexplored in HIV and cocaine-exposed microglia. We assessed the potential of 4-octyl-itaconate (4OI), a cell-penetrable ester form of itaconate known for its anti-inflammatory properties. When primary cortical cultures exposed to Tat and cocaine were treated with 4OI, microglial cell number increased and the morphological altercations induced by Tat and cocaine were reversed. Microglial cells also appeared more ramified, resembling the quiescent microglia. 4OI treatment inhibited secretion of the proinflammatory cytokines IL-1α, IL-1β, IL-6, and MIP1-α induced by Tat and cocaine. Transcriptome profiling determined that Nrf2 target genes were significantly activated in Tat and 4OI treated cultures relative to Tat alone. Further, genes associated with cytoskeleton dynamics in inflammatory microglia were downregulated by 4OI treatment. Together, the results strongly suggest 4-octyl-itaconate holds promise as a potential candidate for therapeutic development to treat HAND coupled with CUD comorbidities.

Graphical Abstract

Model of 4OI-mediated neuroprotection against Tat-Cocaine toxicity. Tat and Tat-Cocaine treatment induce neuronal damage, which is mitigated by 4OI through microglia cells. This cartoon shows the reduction of harmful effects such as pro-inflammatory cytokine release, upregulation of P2R, PDE, and Acod1 by the presence of 4OI. This ester modified itaconate triggers anti-inflammatory responses and activates antioxidant pathways
Appendix
Available only for authorised users
Literature
go back to reference Aksenov MY, Aksenova MV, Nath A, Ray PD, Mactutus CF, Booze RM (2006) Cocaine-mediated enhancement of Tat toxicity in rat hippocampal cell cultures: the role of oxidative stress and D1 dopamine receptor. Neurotoxicology 27:217–228PubMedCrossRef Aksenov MY, Aksenova MV, Nath A, Ray PD, Mactutus CF, Booze RM (2006) Cocaine-mediated enhancement of Tat toxicity in rat hippocampal cell cultures: the role of oxidative stress and D1 dopamine receptor. Neurotoxicology 27:217–228PubMedCrossRef
go back to reference Aksenova MV, Aksenov MY, Adams SM, Mactutus CF, Booze RM (2009) Neuronal survival and resistance to HIV-1 Tat toxicity in the primary culture of rat fetal neurons. Exp Neurol 215:253–263PubMedCrossRef Aksenova MV, Aksenov MY, Adams SM, Mactutus CF, Booze RM (2009) Neuronal survival and resistance to HIV-1 Tat toxicity in the primary culture of rat fetal neurons. Exp Neurol 215:253–263PubMedCrossRef
go back to reference Aksenova M, Sybrandt J, Cui B, Sikirzhytski V, Ji H, Odhiambo D, Lucius MD, Turner JR, Broude E, Pena E, Lizarraga S, Zhu J, Safro I, Wyatt MD, Shtutman M (2019) Inhibition of the dead box RNA helicase 3 prevents HIV-1 Tat and cocaine-induced neurotoxicity by targeting microglia activation. J Neuroimmune Pharmacol 15(2):209–223PubMedPubMedCentralCrossRef Aksenova M, Sybrandt J, Cui B, Sikirzhytski V, Ji H, Odhiambo D, Lucius MD, Turner JR, Broude E, Pena E, Lizarraga S, Zhu J, Safro I, Wyatt MD, Shtutman M (2019) Inhibition of the dead box RNA helicase 3 prevents HIV-1 Tat and cocaine-induced neurotoxicity by targeting microglia activation. J Neuroimmune Pharmacol 15(2):209–223PubMedPubMedCentralCrossRef
go back to reference Avants SK, Margolin A, McMahon TJ, Kosten TR (1997) Association between self-report of cognitive impairment, HIV status, and cocaine use in a sample of cocaine-dependent methadone-maintained patients. Addict Behav 22:599–611PubMedCrossRef Avants SK, Margolin A, McMahon TJ, Kosten TR (1997) Association between self-report of cognitive impairment, HIV status, and cocaine use in a sample of cocaine-dependent methadone-maintained patients. Addict Behav 22:599–611PubMedCrossRef
go back to reference Bambouskova M, Potuckova L, Paulenda T, Kerndl M, Mogilenko DA, Lizotte K, Swain A, Hayes S, Sheldon RD, Kim H, Kapadnis U, Ellis AE, Isaguirre C, Burdess S, Laha A, Amarasinghe GK, Chubukov V, Roddy TP, Diamond MS, Jones RG, Simons DM, Artyomov MN (2021) Itaconate confers tolerance to late NLRP3 inflammasome activation. Cell Rep 34:108756PubMedPubMedCentralCrossRef Bambouskova M, Potuckova L, Paulenda T, Kerndl M, Mogilenko DA, Lizotte K, Swain A, Hayes S, Sheldon RD, Kim H, Kapadnis U, Ellis AE, Isaguirre C, Burdess S, Laha A, Amarasinghe GK, Chubukov V, Roddy TP, Diamond MS, Jones RG, Simons DM, Artyomov MN (2021) Itaconate confers tolerance to late NLRP3 inflammasome activation. Cell Rep 34:108756PubMedPubMedCentralCrossRef
go back to reference Ben Haij N, Planes R, Leghmari K, Serrero M, Delobel P, Izopet J, BenMohamed L, Bahraoui E (2015) HIV-1 Tat protein induces production of pro-inflammatory cytokines by human dendritic cells and monocytes/macrophages through engagement of TLR4-MD2-CD14 complex and activation of NF-kappaB pathway. PLoS ONE 10:e0129425PubMedPubMedCentralCrossRef Ben Haij N, Planes R, Leghmari K, Serrero M, Delobel P, Izopet J, BenMohamed L, Bahraoui E (2015) HIV-1 Tat protein induces production of pro-inflammatory cytokines by human dendritic cells and monocytes/macrophages through engagement of TLR4-MD2-CD14 complex and activation of NF-kappaB pathway. PLoS ONE 10:e0129425PubMedPubMedCentralCrossRef
go back to reference Bertrand SJ, Hu C, Aksenova MV, Mactutus CF, Booze RM (2015) HIV-1 Tat and cocaine mediated synaptopathy in cortical and midbrain neurons is prevented by the isoflavone Equol. Front Microbiol 6:894PubMedPubMedCentralCrossRef Bertrand SJ, Hu C, Aksenova MV, Mactutus CF, Booze RM (2015) HIV-1 Tat and cocaine mediated synaptopathy in cortical and midbrain neurons is prevented by the isoflavone Equol. Front Microbiol 6:894PubMedPubMedCentralCrossRef
go back to reference Beyrer C, Wirtz AL, Baral S, Peryskina A, Sifakis F (2010) Epidemiologic links between drug use and HIV epidemics: an international perspective. J Acquir Immune Defic Syndr 55(Suppl 1):S10–S16PubMedCrossRef Beyrer C, Wirtz AL, Baral S, Peryskina A, Sifakis F (2010) Epidemiologic links between drug use and HIV epidemics: an international perspective. J Acquir Immune Defic Syndr 55(Suppl 1):S10–S16PubMedCrossRef
go back to reference Biber K, Bhattacharya A, Campbell BM, Piro JR, Rohe M, Staal RGW, Talanian RV, Möller T (2019) Microglial drug targets in AD: opportunities and challenges in drug discovery and development. Front Pharmacol 10:840PubMedPubMedCentralCrossRef Biber K, Bhattacharya A, Campbell BM, Piro JR, Rohe M, Staal RGW, Talanian RV, Möller T (2019) Microglial drug targets in AD: opportunities and challenges in drug discovery and development. Front Pharmacol 10:840PubMedPubMedCentralCrossRef
go back to reference Calovi S, Mut-Arbona P, Sperlagh B (2019) Microglia and the purinergic signaling system. Neuroscience 405:137–147PubMedCrossRef Calovi S, Mut-Arbona P, Sperlagh B (2019) Microglia and the purinergic signaling system. Neuroscience 405:137–147PubMedCrossRef
go back to reference Catale C, Bussone S, Lo Iacono L, Carola V (2019) Microglial alterations induced by psychoactive drugs: A possible mechanism in substance use disorder? Semin Cell Dev Biol 94:164–175PubMedCrossRef Catale C, Bussone S, Lo Iacono L, Carola V (2019) Microglial alterations induced by psychoactive drugs: A possible mechanism in substance use disorder? Semin Cell Dev Biol 94:164–175PubMedCrossRef
go back to reference Daniels BP, Kofman SB, Smith JR, Norris GT, Snyder AG, Kolb JP, Gao X, Locasale JW, Martinez J, Gale M Jr, Loo YM, Oberst A (2019) The Nucleotide Sensor ZBP1 and Kinase RIPK3 induce the Enzyme IRG1 to promote an antiviral metabolic state in neurons. Immunity 50(64–76):e4 Daniels BP, Kofman SB, Smith JR, Norris GT, Snyder AG, Kolb JP, Gao X, Locasale JW, Martinez J, Gale M Jr, Loo YM, Oberst A (2019) The Nucleotide Sensor ZBP1 and Kinase RIPK3 induce the Enzyme IRG1 to promote an antiviral metabolic state in neurons. Immunity 50(64–76):e4
go back to reference Davis BM, Salinas-Navarro M, Cordeiro MF, Moons L, De Groef L (2017) Characterizing microglia activation: a spatial statistics approach to maximize information extraction. Sci Rep 7:1576PubMedPubMedCentralCrossRef Davis BM, Salinas-Navarro M, Cordeiro MF, Moons L, De Groef L (2017) Characterizing microglia activation: a spatial statistics approach to maximize information extraction. Sci Rep 7:1576PubMedPubMedCentralCrossRef
go back to reference Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, Batut P, Chaisson M, Gingeras TR (2013) STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29:15–21PubMedCrossRef Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, Batut P, Chaisson M, Gingeras TR (2013) STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29:15–21PubMedCrossRef
go back to reference Donninelli G, Gessani S, Del Cornò M (2016) Interplay between HIV-1 and Toll-like receptors in human myeloid cells: friend or foe in HIV-1 pathogenesis? J Leukoc Biol 99:97–105PubMedCrossRef Donninelli G, Gessani S, Del Cornò M (2016) Interplay between HIV-1 and Toll-like receptors in human myeloid cells: friend or foe in HIV-1 pathogenesis? J Leukoc Biol 99:97–105PubMedCrossRef
go back to reference Ekdahl CT (2012) Microglial activation – tuning and pruning adult neurogenesis. Front Pharmacol 2012(3):41 Ekdahl CT (2012) Microglial activation – tuning and pruning adult neurogenesis. Front Pharmacol 2012(3):41
go back to reference Flannagan RS, Canton J, Furuya W, Glogauer M, Grinstein S (2014) The phosphatidylserine receptor TIM4 utilizes integrins as coreceptors to effect phagocytosis. Mol Biol Cell 25:1511–1522PubMedPubMedCentralCrossRef Flannagan RS, Canton J, Furuya W, Glogauer M, Grinstein S (2014) The phosphatidylserine receptor TIM4 utilizes integrins as coreceptors to effect phagocytosis. Mol Biol Cell 25:1511–1522PubMedPubMedCentralCrossRef
go back to reference Harper J, Ribeiro SP, Chan CN, Aid M, Deleage C, Micci L, Pino M, Cervasi B, Raghunathan G, Rimmer E, Ayanoglu G, Wu G, Shenvi N, Barnard RJ, Del Prete GQ, Busman-Sahay K, Silvestri G, Kulpa DA, Bosinger SE, Easley KA, Howell BJ, Gorman D, Hazuda DJ, Estes JD, Sekaly RP, Paiardini M (2022) Interleukin-10 contributes to reservoir establishment and persistence in SIV-infected macaques treated with antiretroviral therapy. J Clin Invest 132(8):e155251PubMedPubMedCentralCrossRef Harper J, Ribeiro SP, Chan CN, Aid M, Deleage C, Micci L, Pino M, Cervasi B, Raghunathan G, Rimmer E, Ayanoglu G, Wu G, Shenvi N, Barnard RJ, Del Prete GQ, Busman-Sahay K, Silvestri G, Kulpa DA, Bosinger SE, Easley KA, Howell BJ, Gorman D, Hazuda DJ, Estes JD, Sekaly RP, Paiardini M (2022) Interleukin-10 contributes to reservoir establishment and persistence in SIV-infected macaques treated with antiretroviral therapy. J Clin Invest 132(8):e155251PubMedPubMedCentralCrossRef
go back to reference He WT, Wan H, Hu L, Chen P, Wang X, Huang Z, Yang ZH, Zhong CQ, Han J (2015) Gasdermin D is an executor of pyroptosis and required for interleukin-1β secretion. Cell Res 25:1285–1298PubMedPubMedCentralCrossRef He WT, Wan H, Hu L, Chen P, Wang X, Huang Z, Yang ZH, Zhong CQ, Han J (2015) Gasdermin D is an executor of pyroptosis and required for interleukin-1β secretion. Cell Res 25:1285–1298PubMedPubMedCentralCrossRef
go back to reference Hide I, Shiraki H, Masuda A, Maeda T, Kumagai M, Kunishige N, Yanase Y, Harada K, Tanaka S, Sakai N (2023) P2Y2 receptor mediates dying cell removal via inflammatory activated microglia. J Pharmacol Sci 153:55–67PubMedCrossRef Hide I, Shiraki H, Masuda A, Maeda T, Kumagai M, Kunishige N, Yanase Y, Harada K, Tanaka S, Sakai N (2023) P2Y2 receptor mediates dying cell removal via inflammatory activated microglia. J Pharmacol Sci 153:55–67PubMedCrossRef
go back to reference Holloway OG, Canty AJ, King AE, Ziebell JM (2019) Rod microglia and their role in neurological diseases. Semin Cell Dev Biol 94:96–103PubMedCrossRef Holloway OG, Canty AJ, King AE, Ziebell JM (2019) Rod microglia and their role in neurological diseases. Semin Cell Dev Biol 94:96–103PubMedCrossRef
go back to reference Lampropoulou V, Sergushichev A, Bambouskova M, Nair S, Vincent EE, Loginicheva E, Cervantes-Barragan L, Ma X, Huang SC, Griss T, Weinheimer CJ, Khader S, Randolph GJ, Pearce EJ, Jones RG, Diwan A, Diamond MS, Artyomov MN (2016) Itaconate links inhibition of succinate dehydrogenase with macrophage metabolic remodeling and regulation of inflammation. Cell Metab 24:158–166PubMedPubMedCentralCrossRef Lampropoulou V, Sergushichev A, Bambouskova M, Nair S, Vincent EE, Loginicheva E, Cervantes-Barragan L, Ma X, Huang SC, Griss T, Weinheimer CJ, Khader S, Randolph GJ, Pearce EJ, Jones RG, Diwan A, Diamond MS, Artyomov MN (2016) Itaconate links inhibition of succinate dehydrogenase with macrophage metabolic remodeling and regulation of inflammation. Cell Metab 24:158–166PubMedPubMedCentralCrossRef
go back to reference Liao Y, Smyth GK, Shi W (2014) featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30:923–930PubMedCrossRef Liao Y, Smyth GK, Shi W (2014) featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30:923–930PubMedCrossRef
go back to reference Liao K, Guo M, Niu F, Yang L, Callen SE, Buch S (2016) Cocaine-mediated induction of microglial activation involves the ER stress-TLR2 axis. J Neuroinflammation 13:33PubMedPubMedCentralCrossRef Liao K, Guo M, Niu F, Yang L, Callen SE, Buch S (2016) Cocaine-mediated induction of microglial activation involves the ER stress-TLR2 axis. J Neuroinflammation 13:33PubMedPubMedCentralCrossRef
go back to reference Lin J, Ren J, Gao DS, Dai Y, Yu L (2021) The emerging application of itaconate: promising molecular targets and therapeutic opportunities. Front Chem 9:669308PubMedPubMedCentralCrossRef Lin J, Ren J, Gao DS, Dai Y, Yu L (2021) The emerging application of itaconate: promising molecular targets and therapeutic opportunities. Front Chem 9:669308PubMedPubMedCentralCrossRef
go back to reference Marcus JL, Leyden WA, Alexeeff SE, Anderson AN, Hechter RC, Hu H, Lam JO, Towner WJ, Yuan Q, Horberg MA, Silverberg MJ (2020) Comparison of overall and comorbidity-free life expectancy between insured adults with and without HIV infection, 2000–2016. JAMA Netw Open 3:e207954PubMedPubMedCentralCrossRef Marcus JL, Leyden WA, Alexeeff SE, Anderson AN, Hechter RC, Hu H, Lam JO, Towner WJ, Yuan Q, Horberg MA, Silverberg MJ (2020) Comparison of overall and comorbidity-free life expectancy between insured adults with and without HIV infection, 2000–2016. JAMA Netw Open 3:e207954PubMedPubMedCentralCrossRef
go back to reference McCarthy DJ, Chen Y, Smyth GK (2012) Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation. Nucleic Acids Res 40:4288–4297PubMedPubMedCentralCrossRef McCarthy DJ, Chen Y, Smyth GK (2012) Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation. Nucleic Acids Res 40:4288–4297PubMedPubMedCentralCrossRef
go back to reference Michelucci A, Cordes T, Ghelfi J, Pailot A, Reiling N, Goldmann O, Binz T, Wegner A, Tallam A, Rausell A, Buttini M, Linster CL, Medina E, Balling R, Hiller K (2013) Immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production. Proc Natl Acad Sci U S A 110:7820–7825PubMedPubMedCentralCrossRef Michelucci A, Cordes T, Ghelfi J, Pailot A, Reiling N, Goldmann O, Binz T, Wegner A, Tallam A, Rausell A, Buttini M, Linster CL, Medina E, Balling R, Hiller K (2013) Immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production. Proc Natl Acad Sci U S A 110:7820–7825PubMedPubMedCentralCrossRef
go back to reference Midde NM, Huang X, Gomez AM, Booze RM, Zhan CG, Zhu J (2013) Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. J Neuroimmune Pharmacol 8:975–987PubMedPubMedCentralCrossRef Midde NM, Huang X, Gomez AM, Booze RM, Zhan CG, Zhu J (2013) Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. J Neuroimmune Pharmacol 8:975–987PubMedPubMedCentralCrossRef
go back to reference Mills EL, Ryan DG, Prag HA, Dikovskaya D, Menon D, Zaslona Z, Jedrychowski MP, Costa ASH, Higgins M, Hams E, Szpyt J, Runtsch MC, King MS, McGouran JF, Fischer R, Kessler BM, McGettrick AF, Hughes MM, Carroll RG, Booty LM, Knatko EV, Meakin PJ, Ashford MLJ, Modis LK, Brunori G, Sévin DC, Fallon PG, Caldwell ST, Kunji ERS, Chouchani ET, Frezza C, Dinkova-Kostova AT, Hartley RC, Murphy MP, O’Neill LA (2018) Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1. Nature 556:113–117PubMedPubMedCentralCrossRef Mills EL, Ryan DG, Prag HA, Dikovskaya D, Menon D, Zaslona Z, Jedrychowski MP, Costa ASH, Higgins M, Hams E, Szpyt J, Runtsch MC, King MS, McGouran JF, Fischer R, Kessler BM, McGettrick AF, Hughes MM, Carroll RG, Booty LM, Knatko EV, Meakin PJ, Ashford MLJ, Modis LK, Brunori G, Sévin DC, Fallon PG, Caldwell ST, Kunji ERS, Chouchani ET, Frezza C, Dinkova-Kostova AT, Hartley RC, Murphy MP, O’Neill LA (2018) Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1. Nature 556:113–117PubMedPubMedCentralCrossRef
go back to reference Montaño-Rendón F, Walpole GFW, Krause M, Hammond GRV, Grinstein S, Fairn GD (2022a) PtdIns(3,4)P2, Lamellipodin, and VASP coordinate actin dynamics during phagocytosis in macrophages. J Cell Biol 221(11):e202207042PubMedPubMedCentralCrossRef Montaño-Rendón F, Walpole GFW, Krause M, Hammond GRV, Grinstein S, Fairn GD (2022a) PtdIns(3,4)P2, Lamellipodin, and VASP coordinate actin dynamics during phagocytosis in macrophages. J Cell Biol 221(11):e202207042PubMedPubMedCentralCrossRef
go back to reference Montaño-Rendón F, Walpole GFW, Krause M, Hammond GRV, Grinstein S, Fairn GD (2022b) PtdIns(3,4)P2, Lamellipodin, and VASP coordinate actin dynamics during phagocytosis in macrophages. J Cell Biol 221 Montaño-Rendón F, Walpole GFW, Krause M, Hammond GRV, Grinstein S, Fairn GD (2022b) PtdIns(3,4)P2, Lamellipodin, and VASP coordinate actin dynamics during phagocytosis in macrophages. J Cell Biol 221
go back to reference Murakami S, Motohashi H (2015) Roles of Nrf2 in cell proliferation and differentiation. Free Radic Biol Med 88:168–178PubMedCrossRef Murakami S, Motohashi H (2015) Roles of Nrf2 in cell proliferation and differentiation. Free Radic Biol Med 88:168–178PubMedCrossRef
go back to reference Nath A (2002) Human immunodeficiency virus (HIV) proteins in neuropathogenesis of HIV dementia. J Infect Dis 186(Suppl 2):S193–S198PubMedCrossRef Nath A (2002) Human immunodeficiency virus (HIV) proteins in neuropathogenesis of HIV dementia. J Infect Dis 186(Suppl 2):S193–S198PubMedCrossRef
go back to reference Nath A, Hauser KF, Wojna V, Booze RM, Maragos W, Prendergast M, Cass W, Turchan JT (2002) Molecular basis for interactions of HIV and drugs of abuse. J Acquir Immune Defic Syndr 31(Suppl 2):S62–S69PubMedCrossRef Nath A, Hauser KF, Wojna V, Booze RM, Maragos W, Prendergast M, Cass W, Turchan JT (2002) Molecular basis for interactions of HIV and drugs of abuse. J Acquir Immune Defic Syndr 31(Suppl 2):S62–S69PubMedCrossRef
go back to reference Ni L, Xiao J, Zhang D, Shao Z, Huang C, Wang S, Wu Y, Tian N, Sun L, Wu A, Zhou Y, Wang X, Zhang X (2022) Immune-responsive gene 1/itaconate activates nuclear factor erythroid 2-related factor 2 in microglia to protect against spinal cord injury in mice. Cell Death Dis 13:140PubMedPubMedCentralCrossRef Ni L, Xiao J, Zhang D, Shao Z, Huang C, Wang S, Wu Y, Tian N, Sun L, Wu A, Zhou Y, Wang X, Zhang X (2022) Immune-responsive gene 1/itaconate activates nuclear factor erythroid 2-related factor 2 in microglia to protect against spinal cord injury in mice. Cell Death Dis 13:140PubMedPubMedCentralCrossRef
go back to reference NIDA (2018) Monitoring the Future 2018 Survey Results. National Survey Results on Drug Use, 1975-2023 NIDA (2018) Monitoring the Future 2018 Survey Results. National Survey Results on Drug Use, 1975-2023
go back to reference Olagnier D, Farahani E, Thyrsted J, Blay-Cadanet J, Herengt A, Idorn M, Hait A, Hernaez B, Knudsen A, Iversen MB, Schilling M, Jorgensen SE, Thomsen M, Reinert LS, Lappe M, Hoang HD, Gilchrist VH, Hansen AL, Ottosen R, Nielsen CG, Moller C, van der Horst D, Peri S, Balachandran S, Huang J, Jakobsen M, Svenningsen EB, Poulsen TB, Bartsch L, Thielke AL, Luo Y, Alain T, Rehwinkel J, Alcami A, Hiscott J, Mogensen TH, Paludan SR, Holm CK (2020a) Author Correction: SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate. Nat Commun 11:5419PubMedPubMedCentralCrossRef Olagnier D, Farahani E, Thyrsted J, Blay-Cadanet J, Herengt A, Idorn M, Hait A, Hernaez B, Knudsen A, Iversen MB, Schilling M, Jorgensen SE, Thomsen M, Reinert LS, Lappe M, Hoang HD, Gilchrist VH, Hansen AL, Ottosen R, Nielsen CG, Moller C, van der Horst D, Peri S, Balachandran S, Huang J, Jakobsen M, Svenningsen EB, Poulsen TB, Bartsch L, Thielke AL, Luo Y, Alain T, Rehwinkel J, Alcami A, Hiscott J, Mogensen TH, Paludan SR, Holm CK (2020a) Author Correction: SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate. Nat Commun 11:5419PubMedPubMedCentralCrossRef
go back to reference Olagnier D, Farahani E, Thyrsted J, Blay-Cadanet J, Herengt A, Idorn M, Hait A, Hernaez B, Knudsen A, Iversen MB, Schilling M, Jorgensen SE, Thomsen M, Reinert LS, Lappe M, Hoang HD, Gilchrist VH, Hansen AL, Ottosen R, Nielsen CG, Moller C, van der Horst D, Peri S, Balachandran S, Huang J, Jakobsen M, Svenningsen EB, Poulsen TB, Bartsch L, Thielke AL, Luo Y, Alain T, Rehwinkel J, Alcami A, Hiscott J, Mogensen TH, Paludan SR, Holm CK (2020b) SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate. Nat Commun 11:4938PubMedPubMedCentralCrossRef Olagnier D, Farahani E, Thyrsted J, Blay-Cadanet J, Herengt A, Idorn M, Hait A, Hernaez B, Knudsen A, Iversen MB, Schilling M, Jorgensen SE, Thomsen M, Reinert LS, Lappe M, Hoang HD, Gilchrist VH, Hansen AL, Ottosen R, Nielsen CG, Moller C, van der Horst D, Peri S, Balachandran S, Huang J, Jakobsen M, Svenningsen EB, Poulsen TB, Bartsch L, Thielke AL, Luo Y, Alain T, Rehwinkel J, Alcami A, Hiscott J, Mogensen TH, Paludan SR, Holm CK (2020b) SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate. Nat Commun 11:4938PubMedPubMedCentralCrossRef
go back to reference O’Neill LAJ, Artyomov MN (2019) Itaconate: the poster child of metabolic reprogramming in macrophage function. Nat Rev Immunol 19:273–281PubMedCrossRef O’Neill LAJ, Artyomov MN (2019) Itaconate: the poster child of metabolic reprogramming in macrophage function. Nat Rev Immunol 19:273–281PubMedCrossRef
go back to reference Orlowski D, Soltys Z, Janeczko K (2003) Morphological development of microglia in the postnatal rat brain. A quantitative study. Int J Dev Neurosci 21:445–450PubMedCrossRef Orlowski D, Soltys Z, Janeczko K (2003) Morphological development of microglia in the postnatal rat brain. A quantitative study. Int J Dev Neurosci 21:445–450PubMedCrossRef
go back to reference Osborne O, Peyravian N, Nair M, Daunert S, Toborek M (2020) The paradox of HIV blood-brain barrier penetrance and antiretroviral drug delivery deficiencies. Trends Neurosci 43:695–708PubMedPubMedCentralCrossRef Osborne O, Peyravian N, Nair M, Daunert S, Toborek M (2020) The paradox of HIV blood-brain barrier penetrance and antiretroviral drug delivery deficiencies. Trends Neurosci 43:695–708PubMedPubMedCentralCrossRef
go back to reference Pearse DD, Hughes ZA (2016) PDE4B as a microglia target to reduce neuroinflammation. Glia 64:1698–1709PubMedCrossRef Pearse DD, Hughes ZA (2016) PDE4B as a microglia target to reduce neuroinflammation. Glia 64:1698–1709PubMedCrossRef
go back to reference Puigdellivol M, Milde S, Vilalta A, Cockram TOJ, Allendorf DH, Lee JY, Dundee JM, Pampuscenko K, Borutaite V, Nuthall HN, Brelstaff JH, Spillantini MG, Brown GC (2021) The microglial P2Y(6) receptor mediates neuronal loss and memory deficits in neurodegeneration. Cell Rep 37:110148PubMedPubMedCentralCrossRef Puigdellivol M, Milde S, Vilalta A, Cockram TOJ, Allendorf DH, Lee JY, Dundee JM, Pampuscenko K, Borutaite V, Nuthall HN, Brelstaff JH, Spillantini MG, Brown GC (2021) The microglial P2Y(6) receptor mediates neuronal loss and memory deficits in neurodegeneration. Cell Rep 37:110148PubMedPubMedCentralCrossRef
go back to reference Rébé C, Raveneau M, Chevriaux A, Lakomy D, Sberna AL, Costa A, Bessède G, Athias A, Steinmetz E, Lobaccaro JM, Alves G, Menicacci A, Vachenc S, Solary E, Gambert P, Masson D (2009) Induction of transglutaminase 2 by a liver X receptor/retinoic acid receptor alpha pathway increases the clearance of apoptotic cells by human macrophages. Circ Res 105:393–401PubMedCrossRef Rébé C, Raveneau M, Chevriaux A, Lakomy D, Sberna AL, Costa A, Bessède G, Athias A, Steinmetz E, Lobaccaro JM, Alves G, Menicacci A, Vachenc S, Solary E, Gambert P, Masson D (2009) Induction of transglutaminase 2 by a liver X receptor/retinoic acid receptor alpha pathway increases the clearance of apoptotic cells by human macrophages. Circ Res 105:393–401PubMedCrossRef
go back to reference Robinson MD, McCarthy DJ, Smyth GK (2010) edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26:139–140PubMedCrossRef Robinson MD, McCarthy DJ, Smyth GK (2010) edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26:139–140PubMedCrossRef
go back to reference Samikkannu T, Atluri VS, Nair MP (2016) HIV and cocaine impact glial metabolism: energy sensor AMP-activated protein kinase role in mitochondrial biogenesis and epigenetic remodeling. Sci Rep 6:31784PubMedPubMedCentralCrossRef Samikkannu T, Atluri VS, Nair MP (2016) HIV and cocaine impact glial metabolism: energy sensor AMP-activated protein kinase role in mitochondrial biogenesis and epigenetic remodeling. Sci Rep 6:31784PubMedPubMedCentralCrossRef
go back to reference Saylor D, Dickens AM, Sacktor N, Haughey N, Slusher B, Pletnikov M, Mankowski JL, Brown A, Volsky DJ, McArthur JC (2016) HIV-associated neurocognitive disorder–pathogenesis and prospects for treatment. Nat Rev Neurol 12:234–248PubMedPubMedCentralCrossRef Saylor D, Dickens AM, Sacktor N, Haughey N, Slusher B, Pletnikov M, Mankowski JL, Brown A, Volsky DJ, McArthur JC (2016) HIV-associated neurocognitive disorder–pathogenesis and prospects for treatment. Nat Rev Neurol 12:234–248PubMedPubMedCentralCrossRef
go back to reference Shi J, Zhao Y, Wang K, Shi X, Wang Y, Huang H, Zhuang Y, Cai T, Wang F, Shao F (2015) Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature 526:660–665PubMedCrossRef Shi J, Zhao Y, Wang K, Shi X, Wang Y, Huang H, Zhuang Y, Cai T, Wang F, Shao F (2015) Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature 526:660–665PubMedCrossRef
go back to reference Silva NJ, Dorman LC, Vainchtein ID, Horneck NC, Molofsky AV (2021) In situ and transcriptomic identification of microglia in synapse-rich regions of the developing zebrafish brain. Nat Commun 12:5916PubMedPubMedCentralCrossRef Silva NJ, Dorman LC, Vainchtein ID, Horneck NC, Molofsky AV (2021) In situ and transcriptomic identification of microglia in synapse-rich regions of the developing zebrafish brain. Nat Commun 12:5916PubMedPubMedCentralCrossRef
go back to reference Simpson DSA, Oliver PL (2020) ROS generation in microglia: understanding oxidative stress and inflammation in neurodegenerative disease. Antioxidants (Basel) 9(8):743PubMedCrossRef Simpson DSA, Oliver PL (2020) ROS generation in microglia: understanding oxidative stress and inflammation in neurodegenerative disease. Antioxidants (Basel) 9(8):743PubMedCrossRef
go back to reference Sohail A, Iqbal AA, Sahini N, Chen F, Tantawy M, Waqas SFH, Winterhoff M, Ebensen T, Schultz K, Geffers R, Schughart K, Preusse M, Shehata M, Bahre H, Pils MC, Guzman CA, Mostafa A, Pleschka S, Falk C, Michelucci A, Pessler F (2022a) Correction: Itaconate and derivatives reduce interferon responses and inflammation in influenza A virus infection. PLoS Pathog 18:e1011002PubMedPubMedCentralCrossRef Sohail A, Iqbal AA, Sahini N, Chen F, Tantawy M, Waqas SFH, Winterhoff M, Ebensen T, Schultz K, Geffers R, Schughart K, Preusse M, Shehata M, Bahre H, Pils MC, Guzman CA, Mostafa A, Pleschka S, Falk C, Michelucci A, Pessler F (2022a) Correction: Itaconate and derivatives reduce interferon responses and inflammation in influenza A virus infection. PLoS Pathog 18:e1011002PubMedPubMedCentralCrossRef
go back to reference Sohail A, Iqbal AA, Sahini N, Chen F, Tantawy M, Waqas SFH, Winterhoff M, Ebensen T, Schultz K, Geffers R, Schughart K, Preusse M, Shehata M, Bahre H, Pils MC, Guzman CA, Mostafa A, Pleschka S, Falk C, Michelucci A, Pessler F (2022b) Itaconate and derivatives reduce interferon responses and inflammation in influenza A virus infection. PLoS Pathog 18:e1010219PubMedPubMedCentralCrossRef Sohail A, Iqbal AA, Sahini N, Chen F, Tantawy M, Waqas SFH, Winterhoff M, Ebensen T, Schultz K, Geffers R, Schughart K, Preusse M, Shehata M, Bahre H, Pils MC, Guzman CA, Mostafa A, Pleschka S, Falk C, Michelucci A, Pessler F (2022b) Itaconate and derivatives reduce interferon responses and inflammation in influenza A virus infection. PLoS Pathog 18:e1010219PubMedPubMedCentralCrossRef
go back to reference Sophocleous RA, Ooi L, Sluyter R (2022) The P2X4 receptor: cellular and molecular characteristics of a promising neuroinflammatory target. Int J Mol Sci 23(10):5739PubMedPubMedCentralCrossRef Sophocleous RA, Ooi L, Sluyter R (2022) The P2X4 receptor: cellular and molecular characteristics of a promising neuroinflammatory target. Int J Mol Sci 23(10):5739PubMedPubMedCentralCrossRef
go back to reference Sousa C, Golebiewska A, Poovathingal SK, Kaoma T, Pires-Afonso Y, Martina S, Coowar D, Azuaje F, Skupin A, Balling R, Biber K, Niclou SP, Michelucci A (2018) Single-cell transcriptomics reveals distinct inflammation-induced microglia signatures. EMBO Rep 19:e46171PubMedPubMedCentralCrossRef Sousa C, Golebiewska A, Poovathingal SK, Kaoma T, Pires-Afonso Y, Martina S, Coowar D, Azuaje F, Skupin A, Balling R, Biber K, Niclou SP, Michelucci A (2018) Single-cell transcriptomics reveals distinct inflammation-induced microglia signatures. EMBO Rep 19:e46171PubMedPubMedCentralCrossRef
go back to reference Spiehler VR, Reed D (1985) Brain concentrations of cocaine and benzoylecgonine in fatal cases. J Forensic Sci 30:1003–1011PubMedCrossRef Spiehler VR, Reed D (1985) Brain concentrations of cocaine and benzoylecgonine in fatal cases. J Forensic Sci 30:1003–1011PubMedCrossRef
go back to reference Sreeram S, Ye F, Garcia-Mesa Y, Nguyen K, El Sayed A, Leskov K, Karn J (2022) The potential role of HIV-1 latency in promoting neuroinflammation and HIV-1-associated neurocognitive disorder. Trends Immunol 43:630–639PubMedPubMedCentralCrossRef Sreeram S, Ye F, Garcia-Mesa Y, Nguyen K, El Sayed A, Leskov K, Karn J (2022) The potential role of HIV-1 latency in promoting neuroinflammation and HIV-1-associated neurocognitive disorder. Trends Immunol 43:630–639PubMedPubMedCentralCrossRef
go back to reference Swain A, Bambouskova M, Kim H, Andhey PS, Duncan D, Auclair K, Chubukov V, Simons DM, Roddy TP, Stewart KM, Artyomov MN (2020) Comparative evaluation of itaconate and its derivatives reveals divergent inflammasome and type I interferon regulation in macrophages. Nat Metab 2:594–602PubMedPubMedCentralCrossRef Swain A, Bambouskova M, Kim H, Andhey PS, Duncan D, Auclair K, Chubukov V, Simons DM, Roddy TP, Stewart KM, Artyomov MN (2020) Comparative evaluation of itaconate and its derivatives reveals divergent inflammasome and type I interferon regulation in macrophages. Nat Metab 2:594–602PubMedPubMedCentralCrossRef
go back to reference Sybrandt J, Shtutman M, Safro I (2017) MOLIERE: automatic biomedical hypothesis generation system. KDD : Proc Int Conf Knowl Discov Data Mining 2017:1633–1642 Sybrandt J, Shtutman M, Safro I (2017) MOLIERE: automatic biomedical hypothesis generation system. KDD : Proc Int Conf Knowl Discov Data Mining 2017:1633–1642
go back to reference Sybrandt J, Tyagin I, Shtutman M, Safro I (2020) AGATHA: Automatic Graph Mining And Transformer Based Hypothesis Generation Approach. Assoc Comput Machinery 2757–2764, arXiv:2002.05635v1 Sybrandt J, Tyagin I, Shtutman M, Safro I (2020) AGATHA: Automatic Graph Mining And Transformer Based Hypothesis Generation Approach. Assoc Comput Machinery 2757–2764, arXiv:2002.05635v1
go back to reference Tsuchiya K, Hosojima S, Hara H, Kushiyama H, Mahib MR, Kinoshita T, Suda T (2021) Gasdermin D mediates the maturation and release of IL-1alpha downstream of inflammasomes. Cell Rep 34:108887PubMedCrossRef Tsuchiya K, Hosojima S, Hara H, Kushiyama H, Mahib MR, Kinoshita T, Suda T (2021) Gasdermin D mediates the maturation and release of IL-1alpha downstream of inflammasomes. Cell Rep 34:108887PubMedCrossRef
go back to reference Turchan J, Anderson C, Hauser KF, Sun Q, Zhang J, Liu Y, Wise PM, Kruman I, Maragos W, Mattson MP, Booze R, Nath A (2001) Estrogen protects against the synergistic toxicity by HIV proteins, methamphetamine and cocaine. BMC Neurosci 2:3PubMedPubMedCentralCrossRef Turchan J, Anderson C, Hauser KF, Sun Q, Zhang J, Liu Y, Wise PM, Kruman I, Maragos W, Mattson MP, Booze R, Nath A (2001) Estrogen protects against the synergistic toxicity by HIV proteins, methamphetamine and cocaine. BMC Neurosci 2:3PubMedPubMedCentralCrossRef
go back to reference Walker FR, Nilsson M, Jones K (2013) Acute and chronic stress-induced disturbances of microglial plasticity, phenotype and function. Curr Drug Targets 14:1262–1276PubMedCrossRef Walker FR, Nilsson M, Jones K (2013) Acute and chronic stress-induced disturbances of microglial plasticity, phenotype and function. Curr Drug Targets 14:1262–1276PubMedCrossRef
go back to reference Wallet C, De Rovere M, Van Assche J, Daouad F, De Wit S, Gautier V, Mallon PWG, Marcello A, Van Lint C, Rohr O, Schwartz C (2019) Microglial Cells: The Main HIV-1 Reservoir in the Brain. Front Cell Infect Microbiol 9:362PubMedPubMedCentralCrossRef Wallet C, De Rovere M, Van Assche J, Daouad F, De Wit S, Gautier V, Mallon PWG, Marcello A, Van Lint C, Rohr O, Schwartz C (2019) Microglial Cells: The Main HIV-1 Reservoir in the Brain. Front Cell Infect Microbiol 9:362PubMedPubMedCentralCrossRef
go back to reference Westendorp MO, Frank R, Ochsenbauer C, Stricker K, Dhein J, Walczak H, Debating K-M, Krammer PH (1995) Sensitization of T cells to CD95-mediated apoptosis by HIV-1 Tat and gp120. Nature 375:497–500PubMedCrossRef Westendorp MO, Frank R, Ochsenbauer C, Stricker K, Dhein J, Walczak H, Debating K-M, Krammer PH (1995) Sensitization of T cells to CD95-mediated apoptosis by HIV-1 Tat and gp120. Nature 375:497–500PubMedCrossRef
go back to reference Xiao H, Neuveut C, Tiffany HL, Benkirane M, Rich EA, Murphy PM, Jeang KT (2000) Selective CXCR4 antagonism by Tat: implications for in vivo expansion of coreceptor use by HIV-1. Proc Natl Acad Sci U S A 97:11466–11471PubMedPubMedCentralCrossRef Xiao H, Neuveut C, Tiffany HL, Benkirane M, Rich EA, Murphy PM, Jeang KT (2000) Selective CXCR4 antagonism by Tat: implications for in vivo expansion of coreceptor use by HIV-1. Proc Natl Acad Sci U S A 97:11466–11471PubMedPubMedCentralCrossRef
go back to reference Yuan Y, Huang X, Midde NM, Quizon PM, Sun WL, Zhu J, Zhan CG (2015) Molecular mechanism of HIV-1 Tat interacting with human dopamine transporter. ACS Chem Neurosci 6:658–665PubMedCrossRef Yuan Y, Huang X, Midde NM, Quizon PM, Sun WL, Zhu J, Zhan CG (2015) Molecular mechanism of HIV-1 Tat interacting with human dopamine transporter. ACS Chem Neurosci 6:658–665PubMedCrossRef
go back to reference Zayyad Z, Spudich S (2015) Neuropathogenesis of HIV: from initial neuroinvasion to HIV-associated neurocognitive disorder (HAND). Curr HIV/AIDS Rep 12:16–24PubMedPubMedCentralCrossRef Zayyad Z, Spudich S (2015) Neuropathogenesis of HIV: from initial neuroinvasion to HIV-associated neurocognitive disorder (HAND). Curr HIV/AIDS Rep 12:16–24PubMedPubMedCentralCrossRef
go back to reference Zhao X, Zhang F, Kandel SR, Brau F, He JJ (2022) HIV Tat and cocaine interactively alter genome-wide DNA methylation and gene expression and exacerbate learning and memory impairments. Cell Rep 39:110765PubMedPubMedCentralCrossRef Zhao X, Zhang F, Kandel SR, Brau F, He JJ (2022) HIV Tat and cocaine interactively alter genome-wide DNA methylation and gene expression and exacerbate learning and memory impairments. Cell Rep 39:110765PubMedPubMedCentralCrossRef
go back to reference Zimmer BA, Dobrin CV, Roberts DC (2011) Brain-cocaine concentrations determine the dose self-administered by rats on a novel behaviorally dependent dosing schedule. Neuropsychopharmacology 36:2741–2749PubMedPubMedCentralCrossRef Zimmer BA, Dobrin CV, Roberts DC (2011) Brain-cocaine concentrations determine the dose self-administered by rats on a novel behaviorally dependent dosing schedule. Neuropsychopharmacology 36:2741–2749PubMedPubMedCentralCrossRef
Metadata
Title
Suppression of HIV-TAT and cocaine-induced neurotoxicity and inflammation by cell penetrable itaconate esters
Authors
B. Celia Cui
Marina Aksenova
Aliaksandra Sikirzhytskaya
Diana Odhiambo
Elizaveta Korunova
Vitali Sikirzhytski
Hao Ji
Diego Altomare
Eugenia Broude
Norma Frizzell
Rosemarie Booze
Michael D. Wyatt
Michael Shtutman
Publication date
17-06-2024
Publisher
Springer International Publishing
Published in
Journal of NeuroVirology
Print ISSN: 1355-0284
Electronic ISSN: 1538-2443
DOI
https://doi.org/10.1007/s13365-024-01216-9