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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2005

Open Access 01-12-2005 | Research

5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR) attenuates the expression of LPS- and Aβ peptide-induced inflammatory mediators in astroglia

Authors: Kamesh R Ayasolla, Shailendra Giri, Avtar K Singh, Inderjit Singh

Published in: Journal of Neuroinflammation | Issue 1/2005

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Abstract

Background

Alzheimer's disease (AD) pathology shows characteristic 'plaques' rich in amyloid beta (Aβ) peptide deposits. Inflammatory process-related proteins such as pro-inflammatory cytokines have been detected in AD brain suggesting that an inflammatory immune reaction also plays a role in the pathogenesis of AD. Glial cells in culture respond to LPS and Aβ stimuli by upregulating the expression of cytokines TNF-α, IL-1β, and IL-6, and also the expression of proinflammatory genes iNOS and COX-2. We have earlier reported that LPS/Aβ stimulation-induced ceramide and ROS generation leads to iNOS expression and nitric oxide production in glial cells. The present study was undertaken to investigate the neuroprotective function of AICAR (a potent activator of AMP-activated protein kinase) in blocking the pro-oxidant/proinflammatory responses induced in primary glial cultures treated with LPS and Aβ peptide.

Methods

To test the anti-inflammatory/anti-oxidant functions of AICAR, we tested its inhibitory potential in blocking the expression of pro-inflammatory cytokines and iNOS, expression of COX-2, generation of ROS, and associated signaling following treatment of glial cells with LPS and Aβ peptide. We also investigated the neuroprotective effects of AICAR against the effects of cytokines and inflammatory mediators (released by the glia), in blocking neurite outgrowth inhibition, and in nerve growth factor-(NGF) induced neurite extension by PC-12 cells.

Results

AICAR blocked LPS/Aβ-induced inflammatory processes by blocking the expression of proinflammatory cytokine, iNOS, COX-2 and MnSOD genes, and by inhibition of ROS generation and depletion of glutathione in astroglial cells. AICAR also inhibited down-stream signaling leading to the regulation of transcriptional factors such as NFκB and C/EBP which are critical for the expression of iNOS, COX-2, MnSOD and cytokines (TNF-α/IL-1β and IL-6). AICAR promoted NGF-induced neurite growth and reduced neurite outgrowth inhibition in PC-12 cells treated with astroglial conditioned medium.

Conclusion

The observed anti-inflammatory/anti-oxidant and neuroprotective functions of AICAR suggest it as a viable candidate for use in treatment of Alzheimer's disease.
Appendix
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Literature
1.
Selkoe DJ: Alzheimer's disease results from the cerebral accumulation and cytotoxicity of amyloid beta-protein. J Alzheimers Dis. 2001, 3: 75-80.PubMed
2.
Abramov AY, Canevari L, Duchen MR: Beta-amyloid peptides induce mitochondrial dysfunction and oxidative stress in astrocytes and death of neurons through activation of NADPH oxidase. J Neurosci. 2004, 24: 565-575. 10.1523/JNEUROSCI.4042-03.2004.CrossRefPubMed
3.
McGeer EG, McGeer PL: Inflammatory processes in Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry. 2003, 27: 741-749. 10.1016/S0278-5846(03)00124-6.CrossRefPubMed
4.
Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, Cooper NR, Eikelenboom P, Emmerling M, Fiebich BL, Finch CE, Frautschy S, Griffin WS, Hampel H, Hull M, Landreth G, Lue L, Mrak R, Mackenzie IR, McGeer PL, O'Banion MK, Pachter J, Pasinetti G, Plata-Salaman C, Rogers J, Rydel R, Shen Y, Streit W, Strohmeyer R, Tooyoma I, Van Muiswinkel FL, Veerhuis R, Walker D, Webster S, Wegrzyniak B, Wenk G, Wyss-Coray T: Inflammation and Alzheimer's disease. Neurobiol Aging. 2000, 21: 383-421. 10.1016/S0197-4580(00)00124-X.PubMedCentralCrossRefPubMed
5.
Tsukamoto E, Hashimoto Y, Kanekura K, Niikura T, Aiso S, Nishimoto I: Characterization of the toxic mechanism triggered by Alzheimer's amyloid-beta peptides via p75 neurotrophin receptor in neuronal hybrid cells. J Neurosci Res. 2003, 73: 627-636. 10.1002/jnr.10703.CrossRefPubMed
6.
Minagar A, Shapshak P, Fujimura R, Ownby R, Heyes M, Eisdorfer C: The role of macrophage/microglia and astrocytes in the pathogenesis of three neurologic disorders: HIV-associated dementia, Alzheimer disease, and multiple sclerosis. J Neurol Sci. 2002, 202: 13-23. 10.1016/S0022-510X(02)00207-1.CrossRefPubMed
7.
Cordle A, Landreth G: 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors attenuate beta-amyloid-induced microglial inflammatory responses. J Neurosci. 2005, 25: 299-307. 10.1523/JNEUROSCI.2544-04.2005.CrossRefPubMed
8.
Kim SH, Smith CJ, Van Eldik LJ: Importance of MAPK pathways for microglial pro-inflammatory cytokine IL-1 beta production. Neurobiol Aging. 2004, 25: 431-439. 10.1016/S0197-4580(03)00126-X.CrossRefPubMed
9.
Monsonego A, Imitola J, Zota V, Oida T, Weiner HL: Microglia-mediated nitric oxide cytotoxicity of T cells following amyloid beta-peptide presentation to Th1 cells. J Immunol. 2003, 171: 2216-2224.CrossRefPubMed
10.
Rampe D, Wang L, Ringheim GE: P2X7 receptor modulation of beta-amyloid- and LPS-induced cytokine secretion from human macrophages and microglia. J Neuroimmunol. 2004, 147: 56-61. 10.1016/j.jneuroim.2003.10.014.CrossRefPubMed
11.
Monsonego A, Weiner HL: Immunotherapeutic approaches to Alzheimer's disease. Science. 2003, 302: 834-838. 10.1126/science.1088469.CrossRefPubMed
12.
Ayasolla K, Khan M, Singh AK, Singh I: Inflammatory mediator and beta-amyloid (25-35)-induced ceramide generation and iNOS expression are inhibited by vitamin E. Free Radic Biol Med. 2004, 37: 325-338. 10.1016/j.freeradbiomed.2004.04.007.CrossRefPubMed
13.
Tran MH, Yamada K, Nakajima A, Mizuno M, He J, Kamei H, Nabeshima T: Tyrosine nitration of a synaptic protein synaptophysin contributes to amyloid beta-peptide-induced cholinergic dysfunction. Mol Psychiatry. 2003, 8: 407-412. 10.1038/sj.mp.4001240.CrossRefPubMed
14.
Salt IP, Johnson G, Ashcroft SJ, Hardie DG: AMP-activated protein kinase is activated by low glucose in cell lines derived from pancreatic beta cells, and may regulate insulin release. Biochem J. 1998, 335 ( Pt 3): 533-539.CrossRef
15.
Blazquez C, Geelen MJ, Velasco G, Guzman M: The AMP-activated protein kinase prevents ceramide synthesis de novo and apoptosis in astrocytes. FEBS Lett. 2001, 489: 149-153. 10.1016/S0014-5793(01)02089-0.CrossRefPubMed
16.
Hardie DG, Carling D: The AMP-activated protein kinase--fuel gauge of the mammalian cell?. Eur J Biochem. 1997, 246: 259-273. 10.1111/j.1432-1033.1997.00259.x.CrossRefPubMed
17.
Woods A, Johnstone SR, Dickerson K, Leiper FC, Fryer LG, Neumann D, Schlattner U, Wallimann T, Carlson M, Carling D: LKB1 is the upstream kinase in the AMP-activated protein kinase cascade. Curr Biol. 2003, 13: 2004-2008. 10.1016/j.cub.2003.10.031.CrossRefPubMed
18.
Olsen GS, Hansen BF: AMP kinase activation ameliorates insulin resistance induced by free fatty acids in rat skeletal muscle. Am J Physiol Endocrinol Metab. 2002, 283: E965-70.CrossRefPubMed
19.
Giri S, Nath N, Smith B, Viollet B, Singh AK, Singh I: 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside inhibits proinflammatory response in glial cells: a possible role of AMP-activated protein kinase. J Neurosci. 2004, 24: 479-487. 10.1523/JNEUROSCI.4288-03.2004.CrossRefPubMed
20.
Behl C, Moosmann B: Antioxidant neuroprotection in Alzheimer's disease as preventive and therapeutic approach. Free Radic Biol Med. 2002, 33: 182-191. 10.1016/S0891-5849(02)00883-3.CrossRefPubMed
21.
Pahan K, Sheikh FG, Namboodiri AM, Singh I: Lovastatin and phenylacetate inhibit the induction of nitric oxide synthase and cytokines in rat primary astrocytes, microglia, and macrophages. J Clin Invest. 1997, 100: 2671-2679.PubMedCentralCrossRefPubMed
22.
Pike CJ, Burdick D, Walencewicz AJ, Glabe CG, Cotman CW: Neurodegeneration induced by beta-amyloid peptides in vitro: the role of peptide assembly state. J Neurosci. 1993, 13: 1676-1687.PubMed
23.
Zhao H, Kalivendi S, Zhang H, Joseph J, Nithipatikom K, Vasquez-Vivar J, Kalyanaraman B: Superoxide reacts with hydroethidine but forms a fluorescent product that is distinctly different from ethidium: potential implications in intracellular fluorescence detection of superoxide. Free Radic Biol Med. 2003, 34: 1359-1368. 10.1016/S0891-5849(03)00142-4.CrossRefPubMed
24.
Dignam JD, Lebovitz RM, Roeder RG: Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983, 11: 1475-1489.PubMedCentralCrossRefPubMed
25.
Khan M, Sekhon B, Jatana M, Giri S, Gilg AG, Sekhon C, Singh I, Singh AK: Administration of N-acetylcysteine after focal cerebral ischemia protects brain and reduces inflammation in a rat model of experimental stroke. J Neurosci Res. 2004, 76: 519-527. 10.1002/jnr.20087.CrossRefPubMed
26.
Paintlia AS, Paintlia MK, Singh AK, Stanislaus R, Gilg AG, Barbosa E, Singh I: Regulation of gene expression associated with acute experimental autoimmune encephalomyelitis by Lovastatin. J Neurosci Res. 2004, 77: 63-81. 10.1002/jnr.20130.CrossRefPubMed
27.
Dikic I, Schlessinger J, Lax I: PC12 cells overexpressing the insulin receptor undergo insulin-dependent neuronal differentiation. Curr Biol. 1994, 4: 702-708. 10.1016/S0960-9822(00)00155-X.CrossRefPubMed
28.
Minagar A, Shapshak P, Heyes M, Sheremata WA, Fujimara R, Ownby R, Goodkin K, Eisdorfer K: Microglia and astrocytes in neuro-AIDS, alzheimers disease, and multiple sclerosis. ScientificWorldJournal. 2001, 1: 69-CrossRef
29.
Gasic-Milenkovic J, Dukic-Stefanovic S, Deuther-Conrad W, Gartner U, Munch G: Beta-amyloid peptide potentiates inflammatory responses induced by lipopolysaccharide, interferon -gamma and 'advanced glycation endproducts' in a murine microglia cell line. Eur J Neurosci. 2003, 17: 813-821. 10.1046/j.1460-9568.2003.02506.x.CrossRefPubMed
30.
Singh I, Pahan K, Khan M, Singh AK: Cytokine-mediated induction of ceramide production is redox-sensitive. Implications to proinflammatory cytokine-mediated apoptosis in demyelinating diseases. J Biol Chem. 1998, 273: 20354-20362. 10.1074/jbc.273.32.20354.CrossRefPubMed
31.
Pahan K, Sheikh FG, Khan M, Namboodiri AM, Singh I: Sphingomyelinase and ceramide stimulate the expression of inducible nitric-oxide synthase in rat primary astrocytes. J Biol Chem. 1998, 273: 2591-2600. 10.1074/jbc.273.5.2591.CrossRefPubMed
32.
Won JS, Im YB, Khan M, Singh AK, Singh I: The role of neutral sphingomyelinase produced ceramide in lipopolysaccharide-mediated expression of inducible nitric oxide synthase. J Neurochem. 2004, 88: 583-593. 10.1046/j.1471-4159.2003.02165.x.CrossRefPubMed
33.
Kamata H, Honda S, Maeda S, Chang L, Hirata H, Karin M: Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases. Cell. 2005, 120: 649-661. 10.1016/j.cell.2004.12.041.CrossRefPubMed
34.
Cutler RG, Kelly J, Storie K, Pedersen WA, Tammara A, Hatanpaa K, Troncoso JC, Mattson MP: Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer's disease. Proc Natl Acad Sci U S A. 2004, 101: 2070-2075. 10.1073/pnas.0305799101.PubMedCentralCrossRefPubMed
35.
Ayasolla K, Singh AK, Singh I: Vitamin E restores amyloid peptide (25-35) induced changes in cellular redox in C6 glioma cells; implications to Alzheimer's disease. Special Edition of free Radical Biology & Medicine; Proceedings of 'XI Biennial meeting of the society of free Radical Research International'. Monduzzi Editore S.p.A-MEDIMOND Inc. C7160487/503
36.
Jhun BS, Jin Q, Oh YT, Kim SS, Kong Y, Cho YH, Ha J, Baik HH, Kang I: 5-Aminoimidazole-4-carboxamide riboside suppresses lipopolysaccharide-induced TNF-alpha production through inhibition of phosphatidylinositol 3-kinase/Akt activation in RAW 264.7 murine macrophages. Biochem Biophys Res Commun. 2004, 318: 372-380. 10.1016/j.bbrc.2004.04.035.CrossRefPubMed
37.
Morrow VA, Foufelle F, Connell JM, Petrie JR, Gould GW, Salt IP: Direct activation of AMP-activated protein kinase stimulates nitric-oxide synthesis in human aortic endothelial cells. J Biol Chem. 2003, 278: 31629-31639. 10.1074/jbc.M212831200.CrossRefPubMed
38.
Lee AK, Sung SH, Kim YC, Kim SG: Inhibition of lipopolysaccharide-inducible nitric oxide synthase, TNF-alpha and COX-2 expression by sauchinone effects on I-kappaBalpha phosphorylation, C/EBP and AP-1 activation. Br J Pharmacol. 2003, 139: 11-20. 10.1038/sj.bjp.0705231.PubMedCentralCrossRefPubMed
39.
Cardinaux JR, Allaman I, Magistretti PJ: Pro-inflammatory cytokines induce the transcription factors C/EBPbeta and C/EBPdelta in astrocytes. Glia. 2000, 29: 91-97. 10.1002/(SICI)1098-1136(20000101)29:1<91::AID-GLIA9>3.0.CO;2-I.CrossRefPubMed
40.
Li X, Massa PE, Hanidu A, Peet GW, Aro P, Savitt A, Mische S, Li J, Marcu KB: IKKalpha, IKKbeta, and NEMO/IKKgamma are each required for the NF-kappa B-mediated inflammatory response program. J Biol Chem. 2002, 277: 45129-45140. 10.1074/jbc.M205165200.PubMedCentralCrossRefPubMed
41.
Spires TL, Hyman BT: Neuronal structure is altered by amyloid plaques. Rev Neurosci. 2004, 15: 267-278.CrossRefPubMed
42.
Mandelkow EM, Stamer K, Vogel R, Thies E, Mandelkow E: Clogging of axons by tau, inhibition of axonal traffic and starvation of synapses. Neurobiol Aging. 2003, 24: 1079-1085. 10.1016/j.neurobiolaging.2003.04.007.CrossRefPubMed
43.
Gilgun-Sherki Y, Melamed E, Offen D: Oxidative stress induced-neurodegenerative diseases: the need for antioxidants that penetrate the blood brain barrier. Neuropharmacology. 2001, 40: 959-975. 10.1016/S0028-3908(01)00019-3.CrossRefPubMed
44.
Lin A, Sekhon C, Sekhon B, Smith A, Chavin K, Orak J, Singh I, Singh A: Attenuation of ischemia-reperfusion injury in a canine model of autologous renal transplantation. Transplantation. 2004, 78: 654-659. 10.1097/01.TP.0000131664.18670.17.CrossRefPubMed
45.
Nath N, Giri S, Prasad R, Salem ML, Singh AK, Singh I: 5-aminoimidazole-4-carboxamide ribonucleoside: a novel immunomodulator with therapeutic efficacy in experimental autoimmune encephalomyelitis. J Immunol. 2005, 175: 566-574.CrossRefPubMed
46.
Kemp BE, Stapleton D, Campbell DJ, Chen ZP, Murthy S, Walter M, Gupta A, Adams JJ, Katsis F, Van Denderen B, Jennings IG, Iseli T, Michell BJ, Witters LA: AMP-activated protein kinase, super metabolic regulator. Biochem Soc Trans. 2003, 31: 162-168.CrossRefPubMed
47.
Chen HC, Bandyopadhyay G, Sajan MP, Kanoh Y, Standaert M, Farese RVJ, Farese RV: Activation of the ERK pathway and atypical protein kinase C isoforms in exercise- and aminoimidazole-4-carboxamide-1-beta-D-riboside (AICAR)-stimulated glucose transport. J Biol Chem. 2002, 277: 23554-23562. 10.1074/jbc.M201152200.CrossRefPubMed
48.
Halse R, Fryer LG, McCormack JG, Carling D, Yeaman SJ: Regulation of glycogen synthase by glucose and glycogen: a possible role for AMP-activated protein kinase. Diabetes. 2003, 52: 9-15.CrossRefPubMed
49.
Iglesias MA, Ye JM, Frangioudakis G, Saha AK, Tomas E, Ruderman NB, Cooney GJ, Kraegen EW: AICAR administration causes an apparent enhancement of muscle and liver insulin action in insulin-resistant high-fat-fed rats. Diabetes. 2002, 51: 2886-2894.CrossRefPubMed
50.
Bolster DR, Crozier SJ, Kimball SR, Jefferson LS: AMP-activated protein kinase suppresses protein synthesis in rat skeletal muscle through down-regulated mammalian target of rapamycin (mTOR) signaling. J Biol Chem. 2002, 277: 23977-23980. 10.1074/jbc.C200171200.CrossRefPubMed
51.
Barthel A, Schmoll D, Kruger KD, Roth RA, Joost HG: Regulation of the forkhead transcription factor FKHR (FOXO1a) by glucose starvation and AICAR, an activator of AMP-activated protein kinase. Endocrinology. 2002, 143: 3183-3186. 10.1210/en.143.8.3183.CrossRefPubMed
52.
Henin N, Vincent MF, Gruber HE, Van den Berghe G: Inhibition of fatty acid and cholesterol synthesis by stimulation of AMP-activated protein kinase. Faseb J. 1995, 9: 541-546.PubMed
53.
Wu G, Fang YZ, Yang S, Lupton JR, Turner ND: Glutathione metabolism and its implications for health. J Nutr. 2004, 134: 489-492.PubMed
54.
Floyd RA: Antioxidants, oxidative stress, and degenerative neurological disorders. Proc Soc Exp Biol Med. 1999, 222: 236-245. 10.1046/j.1525-1373.1999.d01-140.x.CrossRefPubMed
55.
Sugaya K, Uz T, Kumar V, Manev H: New anti-inflammatory treatment strategy in Alzheimer's disease. Jpn J Pharmacol. 2000, 82: 85-94. 10.1254/jjp.82.85.CrossRefPubMed
56.
Weldon DT, Maggio JE, Mantyh PW: New insights into the neuropathology and cell biology of Alzheimer's disease. Geriatrics. 1997, 52 Suppl 2: S13-6.PubMed
57.
Luth HJ, Munch G, Arendt T: Aberrant expression of NOS isoforms in Alzheimer's disease is structurally related to nitrotyrosine formation. Brain Res. 2002, 953: 135-143. 10.1016/S0006-8993(02)03280-8.CrossRefPubMed
58.
Pasinetti GM, Aisen PS: Cyclooxygenase-2 expression is increased in frontal cortex of Alzheimer's disease brain. Neuroscience. 1998, 87: 319-324. 10.1016/S0306-4522(98)00218-8.CrossRefPubMed
59.
Aisen PS: Evaluation of selective COX-2 inhibitors for the treatment of Alzheimer's disease. J Pain Symptom Manage. 2002, 23: S35-40. 10.1016/S0885-3924(02)00374-3.CrossRefPubMed
60.
61.
Carlson NG: Neuroprotection of cultured cortical neurons mediated by the cyclooxygenase-2 inhibitor APHS can be reversed by a prostanoid. J Neurosci Res. 2003, 71: 79-88. 10.1002/jnr.10465.CrossRefPubMed
62.
Qin W, Ho L, Pompl PN, Peng Y, Zhao Z, Xiang Z, Robakis NK, Shioi J, Suh J, Pasinetti GM: Cyclooxygenase (COX)-2 and COX-1 potentiate beta-amyloid peptide generation through mechanisms that involve gamma-secretase activity. J Biol Chem. 2003, 278: 50970-50977. 10.1074/jbc.M307699200.CrossRefPubMed
63.
Candelario-Jalil E, Alvarez D, Castaneda JM, Al-Dalain SM, Martinez-Sanchez G, Merino N, Leon OS: The highly selective cyclooxygenase-2 inhibitor DFU is neuroprotective when given several hours after transient cerebral ischemia in gerbils. Brain Res. 2002, 927: 212-215. 10.1016/S0006-8993(01)03358-3.CrossRefPubMed
64.
Khayyam N, Thavendiranathan P, Carmichael FJ, Kus B, Jay V, Burnham WM: Neuroprotective effects of acetylsalicylic acid in an animal model of focal brain ischemia. Neuroreport. 1999, 10: 371-374.CrossRefPubMed
65.
Hwang DY, Chae KR, Kang TS, Hwang JH, Lim CH, Kang HK, Goo JS, Lee MR, Lim HJ, Min SH, Cho JY, Hong JT, Song CW, Paik SG, Cho JS, Kim YK: Alterations in behavior, amyloid beta-42, caspase-3, and Cox-2 in mutant PS2 transgenic mouse model of Alzheimer's disease. Faseb J. 2002, 16: 805-813. 10.1096/fj.01-0732com.CrossRefPubMed
66.
Bazan NG, Lukiw WJ: Cyclooxygenase-2 and presenilin-1 gene expression induced by interleukin-1beta and amyloid beta 42 peptide is potentiated by hypoxia in primary human neural cells. J Biol Chem. 2002, 277: 30359-30367. 10.1074/jbc.M203201200.CrossRefPubMed
67.
Acarin L, Peluffo H, Gonzalez B, Castellano B: Expression of inducible nitric oxide synthase and cyclooxygenase-2 after excitotoxic damage to the immature rat brain. J Neurosci Res. 2002, 68: 745-754. 10.1002/jnr.10261.CrossRefPubMed
Metadata
Title
5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR) attenuates the expression of LPS- and Aβ peptide-induced inflammatory mediators in astroglia
Authors
Kamesh R Ayasolla
Shailendra Giri
Avtar K Singh
Inderjit Singh
Publication date
01-12-2005
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2005
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/1742-2094-2-21

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