Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2012

Open Access 01-12-2012 | Research

Involvement of PPAR-γ in the neuroprotective and anti-inflammatory effects of angiotensin type 1 receptor inhibition: effects of the receptor antagonist telmisartan and receptor deletion in a mouse MPTP model of Parkinson's disease

Authors: Pablo Garrido-Gil, Belen Joglar, Ana I Rodriguez-Perez, Maria J Guerra, Jose L Labandeira-Garcia

Published in: Journal of Neuroinflammation | Issue 1/2012

Login to get access

Abstract

Background

Several recent studies have shown that angiotensin type 1 receptor (AT1) antagonists such as candesartan inhibit the microglial inflammatory response and dopaminergic cell loss in animal models of Parkinson's disease. However, the mechanisms involved in the neuroprotective and anti-inflammatory effects of AT1 blockers in the brain have not been clarified. A number of studies have reported that AT1 blockers activate peroxisome proliferator-activated receptor gamma (PPAR γ). PPAR-γ activation inhibits inflammation, and may be responsible for neuroprotective effects, independently of AT1 blocking actions.

Methods

We have investigated whether oral treatment with telmisartan (the most potent PPAR-γ activator among AT1 blockers) provides neuroprotection against dopaminergic cell death and neuroinflammation, and the possible role of PPAR-γ activation in any such neuroprotection. We used a mouse model of parkinsonism induced by the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and co-administration of the PPAR-γ antagonist GW9662 to study the role of PPAR-γ activation. In addition, we used AT1a-null mice lesioned with MPTP to study whether deletion of AT1 in the absence of any pharmacological effect of AT1 blockers provides neuroprotection, and investigated whether PPAR-γ activation may also be involved in any such effect of AT1 deletion by co-administration of the PPAR-γ antagonist GW9662.

Results

We observed that telmisartan protects mouse dopaminergic neurons and inhibits the microglial response induced by administration of MPTP. The protective effects of telmisartan on dopaminergic cell death and microglial activation were inhibited by co-administration of GW9662. Dopaminergic cell death and microglial activation were significantly lower in AT1a-null mice treated with MPTP than in mice not subjected to AT1a deletion. Interestingly, the protective effects of AT1 deletion were also inhibited by co-administration of GW9662.

Conclusion

The results suggest that telmisartan provides effective neuroprotection against dopaminergic cell death and that the neuroprotective effect is mediated by PPAR-γ activation. However, the results in AT1-deficient mice show that blockage of AT1, unrelated to the pharmacological properties of AT1 blockers, also protects against dopaminergic cell death and neuroinflammation. Furthermore, the results show that PPAR-γ activation is involved in the anti-inflammatory and neuroprotective effects of AT1 deletion.
Literature
1.
2.
Zhou C, Huang Y, Przedborski S: Oxidative stress in Parkinson's disease: a mechanism of pathogenic and therapeutic significance. Ann N Y Acad Sci 2008, 1147:93–104.CrossRefPubMedPubMedCentral
3.
Cai H, Griendling KK, Harrison DG: The vascular NAD(P)H oxidases as therapeutic targets in cardiovascular diseases. Trends Pharmacol Sci 2003, 24:471–478.CrossRefPubMed
4.
Seshiah PN, Weber DS, Rocic P, Valppu L, Taniyama Y, Griendling KK: Angiotensin II stimulation of NAD(P)H oxidase activity: upstream mediators. Circ Res 2002, 91:406–413.CrossRefPubMed
5.
Touyz RM, Chen X, Tabet F, Yao G, He G, Quinn MT, Pagano PJ, Schiffrin EL: Expression of a functionally active gp91phox-containing neutrophil-type NAD(P)H oxidase in smooth muscle cells from human resistance arteries: regulation by angiotensin II. Circ Res 2002, 90:1205–1213.CrossRefPubMed
6.
Basso N, Paglia N, Stella I, de Cavanagh EM, Ferder L, del Rosario Lores Arnaiz M, Inserra F: Protective effect of the inhibition of the renin-angiotensin system on aging. Regul Pept 2005, 128:247–252.CrossRefPubMed
7.
Heymes C, Silvestre JS, Llorens-Cortes C, Chevalier B, Marotte F, Levy BI, Swynghedauw B, Samuel JL: Cardiac senescence is associated with enhanced expression of angiotensin II receptor subtypes. Endocrinology 1998, 139:2579–2587.PubMed
8.
Touyz RM, Endemann D, He G, Li JS, Schiffrin EL: Role of AT2 receptors in angiotensin II-stimulated contraction of small mesenteric arteries in young SHR. Hypertension 1999, 33:366–372.CrossRefPubMed
9.
McKinley MJ, Albiston AL, Allen AM, Mathai ML, May CN, McAllen RM, Oldfield BJ, Mendelsohn FA, Chai SY: The brain renin-angiotensin system: location and physiological roles. Int J Biochem Cell Biol 2003, 35:901–918.CrossRefPubMed
10.
Saavedra JM: Brain angiotensin II: new developments, unanswered questions and therapeutic opportunities. Cell Mol Neurobiol 2005, 25:485–512.CrossRefPubMed
11.
Joglar B, Rodriguez-Pallares J, Rodriguez-Perez AI, Rey P, Guerra MJ, Labandeira-Garcia JL: The inflammatory response in the MPTP model of Parkinson's disease is mediated by brain angiotensin: relevance to progression of the disease. J Neurochem 2009, 109:656–669.CrossRefPubMed
12.
Grammatopoulos TN, Jones SM, Ahmadi FA, Hoover BR, Snell LD, Skoch J, Jhaveri VV, Poczobutt AM, Weyhenmeyer JA, Zawada WM: Angiotensin type 1 receptor antagonist losartan, reduces MPTP-induced degeneration of dopaminergic neurons in substantia nigra. Mol Neurodegener 2007, 2:1.CrossRefPubMedPubMedCentral
13.
Rodriguez-Pallares J, Rey P, Parga JA, Muñoz A, Guerra MJ, Labandeira-Garcia JL: Brain angiotensin enhances dopaminergic cell death via microglial activation and NADPH-derived ROS. Neurobiol Dis 2008, 31:58–73.CrossRefPubMed
14.
Rey P, Lopez-Real A, Sanchez-Iglesias S, Munoz A, Soto-Otero R, Labandeira-Garcia JL: Angiotensin type-1-receptor antagonists reduce 6-hydroxydopamine toxicity for dopaminergic neurons. Neurobiol Aging 2007, 28:555–567.CrossRefPubMed
15.
Villar-Cheda B, Valenzuela R, Rodriguez-Perez AI, Guerra MJ, Labandeira-Garcia JL: Aging-related changes in the nigral angiotensin system enhances proinflammatory and pro-oxidative markers and 6-OHDA-induced dopaminergic degeneration. Neurobiol Aging 2012,33(1):e1–11.CrossRefPubMed
16.
Rodriguez-Perez AI, Valenzuela R, Villar-Cheda B, Guerra MJ, Labandeira-Garcia JL: Dopaminergic neuroprotection of hormonal replacement therapy in young and aged menopausal rats: role of the brain angiotensin system. Brain 2012, 135:124–138.CrossRefPubMed
17.
Lu Q, Zhu YZ, Wong PT: Neuroprotective effects of candesartan against cerebral ischemia in spontaneously hypertensive rats. Neuroreport 2005, 16:1963–1967.CrossRefPubMed
18.
Hamai M, Iwai M, Ide A, Tomochika H, Tomono Y, Mogi M, Horiuchi M: Comparison of inhibitory action of candesartan and enalapril on brain ischemia through inhibition of oxidative stress. Neuropharmacology 2006, 51:822–828.CrossRefPubMed
19.
Clasen R, Schupp M, Foryst-Ludwig A, Sprang C, Clemenz M, Krikov M, Thone-Reineke C, Unger T, Kintscher U: PPARgamma-activating angiotensin type-1 receptor blockers induce adiponectin. Hypertension 2005, 46:137–143.CrossRefPubMed
20.
Erbe DV, Gartrell K, Zhang YL, Suri V, Kirincich SJ, Will S, Perreault M, Wang S, Tobin JF: Molecular activation of PPARgamma by angiotensin II type 1-receptor antagonists. Vascul Pharmacol 2006, 45:154–162.CrossRefPubMed
21.
Schupp M, Janke J, Clasen R, Unger T, Kintscher U: Angiotensin type 1 receptor blockers induce peroxisome proliferator-activated receptor-gamma activity. Circulation 2004, 109:2054–2057.CrossRefPubMed
22.
Delerive P, Fruchart JC, Staels B: Peroxisome proliferator-activated receptors in inflammation control. J Endocrinol 2001, 169:453–459.CrossRefPubMed
23.
Jiang C, Ting AT, Seed B: PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 1998, 391:82–86.CrossRefPubMed
24.
Ricote M, Li AC, Willson TM, Kelly CJ, Glass CK: The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature 1998, 391:79–82.CrossRefPubMed
25.
Bernardo A, Levi G, Minghetti L: Role of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and its natural ligand 15-deoxy-Delta12, 14-prostaglandin J2 in the regulation of microglial functions. Eur J Neurosci 2000, 12:2215–2223.CrossRefPubMed
26.
Moreno S, Farioli-Vecchioli S, Ceru MP: Immunolocalization of peroxisome proliferator-activated receptors and retinoid × receptors in the adult rat CNS. Neuroscience 2004, 123:131–145.CrossRefPubMed
27.
28.
Breidert T, Callebert J, Heneka MT, Landreth G, Launay JM, Hirsch EC: Protective action of the peroxisome proliferator-activated receptor-gamma agonist pioglitazone in a mouse model of Parkinson's disease. J Neurochem 2002, 82:615–624.CrossRefPubMed
29.
Schintu N, Frau L, Ibba M, Caboni P, Garau A, Carboni E, Carta AR: PPAR-gamma-mediated neuroprotection in a chronic mouse model of Parkinson's disease. Eur J Neurosci 2009, 29:954–963.CrossRefPubMed
30.
Kurtz TW: Treating the metabolic syndrome: telmisartan as a peroxisome proliferator-activated receptor-gamma activator. Acta Diabetol 2005,42(Suppl 1):S9-S16.CrossRefPubMed
31.
Nabeshima Y, Tazuma S, Kanno K, Hyogo H, Chayama K: Deletion of angiotensin II type I receptor reduces hepatic steatosis. J Hepatol 2009, 50:1226–1235.CrossRefPubMed
32.
Sugaya T, Nishimatsu S, Tanimoto K, Takimoto E, Yamagishi T, Imamura K, Goto S, Imaizumi K, Hisada Y, Otsuka A, et al.: Angiotensin II type 1a receptor-deficient mice with hypotension and hyperreninemia. J Biol Chem 1995, 270:18719–18722.CrossRefPubMed
33.
Gohlke P, Weiss S, Jansen A, Wienen W, Stangier J, Rascher W, Culman J, Unger T: AT1 receptor antagonist telmisartan administered peripherally inhibits central responses to angiotensin II in conscious rats. J Pharmacol Exp Ther 2001, 298:62–70.PubMed
34.
Haraguchi T, Takasaki K, Naito T, Hayakawa K, Katsurabayashi S, Mishima K, Iwasaki K, Fujiwara M: Cerebroprotective action of telmisartan by inhibition of macrophages/microglia expressing HMGB1 via a peroxisome proliferator-activated receptor gamma-dependent mechanism. Neurosci Lett 2009, 464:151–155.CrossRefPubMed
35.
Kasahara Y, Taguchi A, Uno H, Nakano A, Nakagomi T, Hirose H, Stern DM, Matsuyama T: Telmisartan suppresses cerebral injury in a murine model of transient focal ischemia. Brain Res 2010, 1340:70–80.CrossRefPubMed
36.
Hows MEP, Ashmeade TE, Billinton A, Perren MJ, Austin AA, Virley DJ, Organ AJ, Shah AJ: High-performance liquid chromatography/tandem mass spectrometry assay for the determination of 1-methyl-4-phenyl pyridium (MPP + ) in brain tissue homogenates. J Neurosci Methods 2004, 137:221–226.CrossRefPubMed
37.
Przedborski S, Jackson-Lewis V, Yokoyama R, Shibata T, Dawson VL, Dawson TM: Role of neuronal nitric oxide in 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity. Proc Natl Acad Sci USA 1996, 93:4565–4571.CrossRefPubMedPubMedCentral
38.
Gundersen HJ, Bendtsen TF, Korbo L, Marcussen N, Moller A, Nielsen K, Nyengaard JR, Pakkenberg B, Sorensen FB, Vesterby A, West MJ: Some new, simple and efficient stereological methods and their use in pathological research and diagnosis. APMIS 1988, 96:379–394.CrossRefPubMed
39.
Torres EM, Meldrum A, Kirik D, Dunnett SB: An investigation of the problem of two-layered immunohistochemical staining in paraformaldehyde fixed sections. J Neurosci Methods 2006, 158:64–74.CrossRefPubMed
40.
Jung KH, Chu K, Lee ST, Kim SJ, Song EC, Kim EH, Park DK, Sinn DI, Kim JM, Kim M, Roh JK: Blockade of AT1 receptor reduces apoptosis, inflammation, and oxidative stress in normotensive rats with intracerebral hemorrhage. J Pharmacol Exp Ther 2007, 322:1051–1058.CrossRefPubMed
41.
Kuipers I, van der Harst P, Navis G, van Genne L, Morello F, van Gilst WH, van Veldhuisen DJ, de Boer RA: Nuclear hormone receptors as regulators of the renin-angiotensin-aldosterone system. Hypertension 2008, 51:1442–1448.CrossRefPubMed
42.
Zorad S, Dou JT, Benicky J, Hutanu D, Tybitanclova K, Zhou J, Saavedra JM: Long-term angiotensin II AT1 receptor inhibition produces adipose tissue hypotrophy accompanied by increased expression of adiponectin and PPARgamma. Eur J Pharmacol 2006, 552:112–122.CrossRefPubMedPubMedCentral
43.
Kintscher U, Lyon CJ, Law RE: Angiotensin II, PPAR-gamma and atherosclerosis. Front Biosci 2004, 9:359–369.CrossRefPubMed
44.
Tham DM, Martin-McNulty B, Wang YX, Wilson DW, Vergona R, Sullivan ME, Dole W, Rutledge JC: Angiotensin II is associated with activation of NF-kappaB-mediated genes and downregulation of PPARs. Physiol Genomics 2002, 11:21–30.CrossRefPubMed
45.
Santos EL, de Picoli Souza K, da Silva ED, Batista EC, Martins PJ, D'Almeida V, Pesquero JB: Long term treatment with ACE inhibitor enalapril decreases body weight gain and increases life span in rats. Biochem Pharmacol 2009, 78:951–958.CrossRefPubMed
46.
Storka A, Vojtassakova E, Mueller M, Kapiotis S, Haider DG, Jungbauer A, Wolzt M: Angiotensin inhibition stimulates PPARgamma and the release of visfatin. Eur J Clin Invest 2008, 38:820–826.CrossRefPubMed
47.
Zhao Y, Foryst-Ludwig A, Bruemmer D, Culman J, Bader M, Unger T, Kintscher U: Angiotensin II induces peroxisome proliferator-activated receptor gamma in PC12W cells via angiotensin type 2 receptor activation. J Neurochem 2005, 94:1395–1401.CrossRefPubMed
48.
Wu L, Iwai M, Nakagami H, Li Z, Chen R, Suzuki J, Akishita M, de Gasparo M, Horiuchi M: Roles of angiotensin II type 2 receptor stimulation associated with selective angiotensin II type 1 receptor blockade with valsartan in the improvement of inflammation-induced vascular injury. Circulation 2001, 104:2716–2721.CrossRefPubMed
49.
Imayama I, Ichiki T, Inanaga K, Ohtsubo H, Fukuyama K, Ono H, Hashiguchi Y, Sunagawa K: Telmisartan downregulates angiotensin II type 1 receptor through activation of peroxisome proliferator-activated receptor gamma. Cardiovasc Res 2006, 72:184–190.CrossRefPubMed
50.
Sugawara A, Takeuchi K, Uruno A, Ikeda Y, Arima S, Kudo M, Sato K, Taniyama Y, Ito S: Transcriptional suppression of type 1 angiotensin II receptor gene expression by peroxisome proliferator-activated receptor-gamma in vascular smooth muscle cells. Endocrinology 2001, 142:3125–3134.PubMed
51.
Takeda K, Ichiki T, Tokunou T, Funakoshi Y, Iino N, Hirano K, Kanaide H, Takeshita A: Peroxisome proliferator-activated receptor gamma activators downregulate angiotensin II type 1 receptor in vascular smooth muscle cells. Circulation 2000, 102:1834–1839.CrossRefPubMed
52.
Takai S, Jin D, Kimura M, Kirimura K, Sakonjo H, Tanaka K, Miyazaki M: Inhibition of vascular angiotensin-converting enzyme by telmisartan via the peroxisome proliferator-activated receptor gamma agonistic property in rats. Hypertens Res 2007, 30:1231–1237.CrossRefPubMed
53.
Banks T, Oyekan A: Peroxisome proliferator-activated receptor alpha activation attenuated angiotensin type 1-mediated but enhanced angiotensin type 2-mediated hemodynamic effects to angiotensin II in the rat. J Hypertens 2008, 26:468–477.CrossRefPubMed
54.
Diep QN, Amiri F, Touyz RM, Cohn JS, Endemann D, Neves MF, Schiffrin EL: PPARalpha activator effects on Ang II-induced vascular oxidative stress and inflammation. Hypertension 2002, 40:866–871.CrossRefPubMed
55.
Ji Y, Liu J, Wang Z, Liu N, Gou W: PPARgamma agonist, rosiglitazone, regulates angiotensin II-induced vascular inflammation through the TLR4-dependent signaling pathway. Lab Invest 2009, 89:887–902.CrossRefPubMed
56.
Chabrashvili T, Kitiyakara C, Blau J, Karber A, Aslam S, Welch WJ, Wilcox CS: Effects of ANG II type 1 and 2 receptors on oxidative stress, renal NADPH oxidase, and SOD expression. Am J Physiol Regul Integr Comp Physiol 2003, 285:R117–124.CrossRefPubMed
57.
Jones ES, Vinh A, McCarthy CA, Gaspari TA, Widdop RE: AT2 receptors: functional relevance in cardiovascular disease. Pharmacol Ther 2008, 120:292–316.CrossRefPubMed
58.
Benigni A, Corna D, Zoja C, Sonzogni A, Latini R, Salio M, Conti S, Rottoli D, Longaretti L, Cassis P, Morigi M, Coffman TM, Remuzzi G: Disruption of the Ang II type 1 receptor promotes longevity in mice. J Clin Invest 2009, 119:524–530.CrossRefPubMedPubMedCentral
59.
de Cavanagh EM, Inserra F, Ferder L: Angiotensin II blockade: a strategy to slow ageing by protecting mitochondria? Cardiovasc Res 2011, 89:31–40.CrossRefPubMed
60.
Umemoto S: Angiotensin II type 1 (AT1) receptor deficiency halts the progression of age-related atherosclerosis in hypercholesterolemia: molecular link between the AT1 receptor and hypercholesterolemia. Hypertens Res 2008, 31:1495–1497.CrossRefPubMed
61.
Bernardo A, Minghetti L: PPAR-gamma agonists as regulators of microglial activation and brain inflammation. Curr Pharm Des 2006, 12:93–109.CrossRefPubMed
62.
Carta AR, Frau L, Pisanu A, Wardas J, Spiga S, Carboni E: Rosiglitazone decreases peroxisome proliferator receptor-gamma levels in microglia and inhibits TNF-alpha production: new evidences on neuroprotection in a progressive Parkinson's disease model. Neuroscience 2011, 194:250–261.CrossRefPubMed
63.
Platten M, Youssef S, Hur EM, Ho PP, Han MH, Lanz TV, Phillips LK, Goldstein MJ, Bhat R, Raine CS, Sobel RA, Steinman L: Blocking angiotensin-converting enzyme induces potent regulatory T cells and modulates TH1- and TH17-mediated autoimmunity. Proc Natl Acad Sci USA 2009, 106:14948–14953.CrossRefPubMedPubMedCentral
64.
Stegbauer J, Lee DH, Seubert S, Ellrichmann G, Manzel A, Kvakan H, Muller DN, Gaupp S, Rump LC, Gold R, Linker RA: Role of the renin-angiotensin system in autoimmune inflammation of the central nervous system. Proc Natl Acad Sci USA 2009, 106:14942–14947.CrossRefPubMedPubMedCentral
65.
Swirski FK, Nahrendorf M, Etzrodt M, Wildgruber M, Cortez-Retamozo V, Panizzi P, Figueiredo JL, Kohler RH, Chudnovskiy A, Waterman P, Aikawa E, Mempel TR, Libby P, Weissleder R, Pittet MJ: Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science 2009,325(5940):612–616.CrossRefPubMedPubMedCentral
66.
Füchtbauer L, Groth-Rasmussen M, Holm TH, Løbner M, Toft-Hansen H, Khorooshi R, Owens T: Angiotensin II Type 1 receptor (AT1) signaling in astrocytes regulates synaptic degeneration-induced leukocyte entry to the central nervous system. Brain Behav Immun 2011, 25:897–904.CrossRefPubMed
67.
Combs CK, Johnson DE, Karlo JC, Cannady SB, Landreth GE: Inflammatory mechanisms in Alzheimer's disease: inhibition of beta-amyloid-stimulated proinflammatory responses and neurotoxicity by PPARgamma agonists. J Neurosci 2000, 20:558–567.PubMed
68.
Jiang Q, Heneka M, Landreth GE: The role of peroxisome proliferator-activated receptor-gamma (PPARgamma) in Alzheimer's disease: therapeutic implications. CNS Drugs 2008, 22:1–14.CrossRefPubMed
69.
Tsukuda K, Mogi M, Iwanami J, Min LJ, Sakata A, Jing F, Iwai M, Horiuchi M: Cognitive deficit in amyloid-beta-injected mice was improved by pretreatment with a low dose of telmisartan partly because of peroxisome proliferator-activated receptor-gamma activation. Hypertension 2009, 54:782–787.CrossRefPubMed
70.
Lou M, Blume A, Zhao Y, Gohlke P, Deuschl G, Herdegen T, Culman J: Sustained blockade of brain AT1 receptors before and after focal cerebral ischemia alleviates neurologic deficits and reduces neuronal injury, apoptosis, and inflammatory responses in the rat. J Cereb Blood Flow Metab 2004, 24:536–547.CrossRefPubMed
71.
Iwanami J, Mogi M, Tsukuda K, Min LJ, Sakata A, Jing F, Iwai M, Horiuchi M: Low dose of telmisartan prevents ischemic brain damage with peroxisome proliferator-activated receptor-gamma activation in diabetic mice. J Hypertens 2010, 28:1730–1737.CrossRefPubMed
72.
Lanz TV, Ding Z, Ho PP, Luo J, Agrawal AN, Srinagesh H, Axtell R, Zhang H, Platten M, Wyss-Coray T, Steinman L: Angiotensin II sustains brain inflammation in mice via TGF-beta. J Clin Invest 2010, 120:2782–2794.CrossRefPubMedPubMedCentral
73.
Yi JH, Park SW, Brooks N, Lang BT, Vemuganti R: PPARgamma agonist rosiglitazone is neuroprotective after traumatic brain injury via anti-inflammatory and anti-oxidative mechanisms. Brain Res 2008, 1244:164–172.CrossRefPubMedPubMedCentral
74.
Loane DJ, Deighan BF, Clarke RM, Griffin RJ, Lynch AM, Lynch MA: Interleukin-4 mediates the neuroprotective effects of rosiglitazone in the aged brain. Neurobiol Aging 2009, 30:920–931.CrossRefPubMed
75.
76.
Mander PK, Jekabsone A, Brown GC: Microglia proliferation is regulated by hydrogen peroxide from NADPH oxidase. J Immunol 2006, 176:1046–1052.CrossRefPubMed
77.
Qin L, Liu Y, Wang T, Wei SJ, Block ML, Wilson B, Liu B, Hong JS: NADPH oxidase mediates lipopolysaccharide-induced neurotoxicity and proinflammatory gene expression in activated microglia. J Biol Chem 2004, 279:1415–1421.CrossRefPubMed
78.
Doughan AK, Harrison DG, Dikalov SI: Molecular mechanisms of angiotensin II-mediated mitochondrial dysfunction: linking mitochondrial oxidative damage and vascular endothelial dysfunction. Circ Res 2008, 102:488–96.CrossRefPubMed
79.
Kimura S, Zhang GX, Nishiyama A, Shokoji T, Yao L, Fan YY, Rahman M, Suzuki T, Maeta H, Abe Y: Role of NAD(P)H oxidase- and mitochondria-derived reactive oxygen species in cardioprotection of ischemic reperfusion injury by angiotensin II. Hypertension 2005, 45:860–866.CrossRefPubMed
80.
Dikalova AE, Bikineyeva AT, Budzyn K, Nazarewicz RR, McCann L, Lewis W, Harrison DG, Dikalov SI: Therapeutic targeting of mitochondrial superoxide in hypertension. Circ Res 2010, 107:106–116.CrossRefPubMedPubMedCentral
81.
Wosniak J Jr, Santos CX, Kowaltowski AJ, Laurindo FR: Cross-talk between mitochondria and NADPH oxidase: effects of mild mitochondrial dysfunction on angiotensin II-mediated increase in Nox isoform expression and activity in vascular smooth muscle cells. Antioxid Redox Signal 2009, 11:1265–1278.CrossRefPubMed
82.
Zawada WM, Banninger GP, Thornton J, Marriott B, Cantu D, Rachubinski AL, Das M, Griffin WS, Jones SM: Generation of reactive oxygen species in 1-methyl-4-phenylpyridinium (MPP+) treated dopaminergic neurons occurs as an NADPH oxidase-dependent two-wave cascade. J Neuroinflammation 2011, 8:129.CrossRefPubMedPubMedCentral
83.
Rodriguez-Pallares J, Parga JA, Joglar B, Guerra MJ, Labandeira-Garcia JL: Mitochondrial ATP-sensitive potassium channels enhance angiotensin-induced oxidative damage and dopaminergic neuron degeneration. Age (Dordr) 2011, in press.
84.
Rodriguez-Pallares J, Parga JA, Joglar B, Guerra MJ, Labandeira-Garcia JL: The mitochondrial ATP-sensitive potassium channel blocker 5-hydroxydecanoate inhibits toxicity of 6-Hydroxydopamine on dopaminergic neurons. Neurotox Res 2009, 15:82–95.CrossRefPubMed
85.
Rodriguez-Pallares J, Parga JA, Muñoz A, Rey P, Guerra MJ, Labandeira-Garcia JL: Mechanism of 6-hydroxydopamine neurotoxicity: the role of NADPH oxidase and microglial activation in 6-hydroxydopamine-induced degeneration of dopaminergic neurons. J Neurochem 2007, 103:145–156.PubMed
86.
Jackson-Lewis V, Jakowec M, Burke RE, Przedborski S: Time course and morphology of dopaminergic neuronal death caused by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Neurodegeneration 1995, 4:257–269.CrossRefPubMed
87.
Wu D, Teisman P, Tieu K, Vila M, Jackson-Lewis V, Ischiropoulos H, Przedborski S: NADPH oxidase mediates oxidative stress in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease. Proc Natl Acad Sci USA 2003, 100:6145–6150.CrossRefPubMedPubMedCentral
Metadata
Title
Involvement of PPAR-γ in the neuroprotective and anti-inflammatory effects of angiotensin type 1 receptor inhibition: effects of the receptor antagonist telmisartan and receptor deletion in a mouse MPTP model of Parkinson's disease
Authors
Pablo Garrido-Gil
Belen Joglar
Ana I Rodriguez-Perez
Maria J Guerra
Jose L Labandeira-Garcia
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2012
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/1742-2094-9-38

Other articles of this Issue 1/2012

Journal of Neuroinflammation 1/2012 Go to the issue

Research

Interaction of HmC1q with leech microglial cells: involvement of C1qBP-related molecule in the induction of cell chemotaxis

Research

Inhibition of Src kinase activity attenuates amyloid associated microgliosis in a murine model of Alzheimer’s disease

Research

NOV/CCN3 attenuates inflammatory pain through regulation of matrix metalloproteinases-2 and -9

Research

Anti-inflammatory recombinant TSG-6 stabilizes the progression of focal retinal degeneration in a murine model

Short report

Targeted blockade in lethal West Nile virus encephalitis indicates a crucial role for very late antigen (VLA)-4-dependent recruitment of nitric oxide-producing macrophages

Research

Relationship between plasma high mobility group box-1 protein levels and clinical outcomes of aneurysmal subarachnoid hemorrhage