Key points are not available for this paper at this time.
Oxidative stress is implicated in the pathogenesis of ischemia/reperfusion injury. Recently, we demonstrated that activation of CD36, a class B scavenger receptor, mediates free radical production and tissue injury in cerebral ischemia (1.Cho S. Park E.M. Febbraio M. Anrather J. Park L. Racchumi G. Silverstein R.L. Iadecola C. J. Neurosci. 2005; 25: 2504-2512Crossref PubMed Scopus (169) Google Scholar). Oxidized low density lipoproteins (oxLDL) are among the ligands that bind to CD36 and are elevated in acute cerebral infarction. SS31 is a cell-permeable antioxidant peptide that reduces intracellular free radicals and inhibits LDL oxidation/lipid peroxidation (2.Zhao K. Zhao G.M. Wu D. Soong Y. Birk A.V. Schiller P.W. Szeto H.H. J. Biol. Chem. 2004; 279: 34682-34690Abstract Full Text Full Text PDF PubMed Scopus (606) Google Scholar). The current study was designed to investigate whether treatment with SS31 normalizes ischemia-induced redox changes and attenuates CD36-mediated tissue injury. C57BL/6 mice were subjected to transient middle cerebral artery occlusion (MCAO). Redox status and infarct volume were measured in animals treated with either saline or SS31. Oxidative stress induced by ischemia/reperfusion profoundly depleted glutathione (GSH) concentrations in the ipsilateral cortex and striatum. Treating mice with SS31 immediately after reperfusion significantly attenuated ischemia-induced GSH depletion in the cortex and reduced infarct size. By contrast, the protective effect of SS31 was absent in CD36 knock-out mice, indicating that SS31 is acting through inhibition of CD36. Treating C57BL/6 mice with SS31 reduced CD36 expression in postischemic brain and mouse peritoneal macrophages (MPM). Further in vitro studies revealed that SS31 attenuated oxLDL-induced CD36 expression and foam cell formation in MPM. These in vivo and in vitro studies indicate that the down-regulation of CD36 by novel class antioxidant peptides may be a useful strategy to treat ischemic stroke victims. Oxidative stress is implicated in the pathogenesis of ischemia/reperfusion injury. Recently, we demonstrated that activation of CD36, a class B scavenger receptor, mediates free radical production and tissue injury in cerebral ischemia (1.Cho S. Park E.M. Febbraio M. Anrather J. Park L. Racchumi G. Silverstein R.L. Iadecola C. J. Neurosci. 2005; 25: 2504-2512Crossref PubMed Scopus (169) Google Scholar). Oxidized low density lipoproteins (oxLDL) are among the ligands that bind to CD36 and are elevated in acute cerebral infarction. SS31 is a cell-permeable antioxidant peptide that reduces intracellular free radicals and inhibits LDL oxidation/lipid peroxidation (2.Zhao K. Zhao G.M. Wu D. Soong Y. Birk A.V. Schiller P.W. Szeto H.H. J. Biol. Chem. 2004; 279: 34682-34690Abstract Full Text Full Text PDF PubMed Scopus (606) Google Scholar). The current study was designed to investigate whether treatment with SS31 normalizes ischemia-induced redox changes and attenuates CD36-mediated tissue injury. C57BL/6 mice were subjected to transient middle cerebral artery occlusion (MCAO). Redox status and infarct volume were measured in animals treated with either saline or SS31. Oxidative stress induced by ischemia/reperfusion profoundly depleted glutathione (GSH) concentrations in the ipsilateral cortex and striatum. Treating mice with SS31 immediately after reperfusion significantly attenuated ischemia-induced GSH depletion in the cortex and reduced infarct size. By contrast, the protective effect of SS31 was absent in CD36 knock-out mice, indicating that SS31 is acting through inhibition of CD36. Treating C57BL/6 mice with SS31 reduced CD36 expression in postischemic brain and mouse peritoneal macrophages (MPM). Further in vitro studies revealed that SS31 attenuated oxLDL-induced CD36 expression and foam cell formation in MPM. These in vivo and in vitro studies indicate that the down-regulation of CD36 by novel class antioxidant peptides may be a useful strategy to treat ischemic stroke victims. Generation of reactive oxygen species (ROS) 2The abbreviations used are: ROS, reactive oxygen species; MCAO, middle cerebral artery occlusion; PBS, phosphate-buffered saline; ANOVA, analysis of variance; MPM, mouse peritoneal macrophages; HPLC, high performance liquid chromatography; MPA, metaphosphoric acid; oxLDL, oxidized low density lipoprotein.2The abbreviations used are: ROS, reactive oxygen species; MCAO, middle cerebral artery occlusion; PBS, phosphate-buffered saline; ANOVA, analysis of variance; MPM, mouse peritoneal macrophages; HPLC, high performance liquid chromatography; MPA, metaphosphoric acid; oxLDL, oxidized low density lipoprotein. and depletion of intracellular antioxidants following cerebral ischemia/reperfusion are hallmarks of oxidative stress and lead to tissue injury. Glutathione and ascorbate are major endogenous cerebral antioxidants that serve as biochemical markers of intracellular redox status (3.Cooper A.J. Pulsinelli W.A. Duffy T.E. J. Neurochem. 1980; 35: 1242-1245Crossref PubMed Scopus (198) Google Scholar). It is generally accepted that these antioxidants are important for protection of brain during post-ischemic oxidative stress, although dynamic interactions among antioxidants in vivo are not entirely clear. Depletion of intracellular antioxidants has been associated with stroke pathology and repletion of antioxidant status has reduced neuronal damage but has produced inconsistent improvement in stroke outcome (4.Namba K. Takeda Y. Sunami K. Hirakawa M. J. Neurosurg. Anesthesiol. 2001; 13: 131-137Crossref PubMed Scopus (33) Google Scholar, 5.Vanella A. Di Giacomo C. Sorrenti V. Russo A. Castorina C. Campisi A. Renis M. Perez-Polo J.R. Neurochem. Res. 1993; 18: 1337-1340Crossref PubMed Scopus (70) Google Scholar, 6.Gotoh O. Yamamoto M. Tamura A. Sano K. Acta. Neurochir. Suppl. (Wien). 1994; 60: 318-320PubMed Google Scholar, 7.Yamamoto M. Sakamoto N. Iwai A. Yatsugi S. Hidaka K. Noguchi K. Yuasa T. Res. Commun. Chem. Pathol. Pharmacol. 1993; 81: 221-232PubMed Google Scholar, 8.Warner D.S. Sheng H. Batinic-Haberle I. J. Exp. Biol. 2004; 207: 3221-3231Crossref PubMed Scopus (503) Google Scholar). Ischemic injury also causes a local inflammatory reaction by activated microglia and infiltrated inflammatory cells that further release pro-inflammatory cytokines and ROS within the injured site. CD36, a glycosylated surface receptor, belongs to a class B scavenger receptor and is localized in lipid rafts of plasma membrane and in mitochondria (9.Bonen A. Campbell S.E. Benton C.R. Chabowski A. Coort S.L. Han X.X. Koonen D.P. Glatz J.F. Luiken J.J. Proc. Nutr. Soc. 2004; 63: 245-249Crossref PubMed Scopus (149) Google Scholar, 10.Campbell S.E. Tandon N.N. Woldegiorgis G. Luiken J.J. Glatz J.F. Bonen A. J. Biol. Chem. 2004; 279: 36235-36241Abstract Full Text Full Text PDF PubMed Scopus (209) Google Scholar, 11.Roepstorff C. Wulff Helge J. Vistisen B. Kiens B. Proc. Nutr. Soc. 2004; 63: 239-244Crossref PubMed Scopus (40) Google Scholar). It is expressed on microglia, macrophages, microvascular endothelium, cardiac and skeletal muscle, adipocytes, and platelets and recognizes a variety of ligands including oxidized low density lipoproteins (oxLDL), advanced glycation end products, long chain fatty acids, fibrillar β-amyloid, thrombospondins, and cells undergoing apoptosis (12.Febbraio M. Hajjar D.P. Silverstein R.L. J. Clin. Investig. 2001; 108: 785-791Crossref PubMed Scopus (904) Google Scholar, 13.Medeiros L.A. Khan T. El Khoury J.B. Pham C.L. Hatters D.M. Howlett G.J. Lopez R. O'Brien K.D. Moore K.J. J. Biol. Chem. 2004; 279: 10643-10648Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar, 14.Hirano K. Kuwasako T. Nakagawa-Toyama Y. Janabi M. Yamashita S. Matsuzawa Y. Trends Cardiovasc. Med. 2003; 13: 136-141Crossref PubMed Scopus (110) Google Scholar). This multifunctional receptor plays a pivotal role in angiogenesis, inflammation, apoptosis, and lipid metabolism (12.Febbraio M. Hajjar D.P. Silverstein R.L. J. Clin. Investig. 2001; 108: 785-791Crossref PubMed Scopus (904) Google Scholar, 14.Hirano K. Kuwasako T. Nakagawa-Toyama Y. Janabi M. Yamashita S. Matsuzawa Y. Trends Cardiovasc. Med. 2003; 13: 136-141Crossref PubMed Scopus (110) Google Scholar). Increased expression of CD36 has been associated with pro-oxidative conditions. Antioxidants, such as α-tocopherol, diminish CD36 expression and reduce the uptake of oxLDL into macrophage (15.Fuhrman B. Volkova N. Aviram M. Atherosclerosis. 2002; 161: 307-316Abstract Full Text Full Text PDF PubMed Scopus (125) Google Scholar, 16.Venugopal S.K. Devaraj S. Jialal I. Atherosclerosis. 2004; 175: 213-220Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar, 17.Ricciarelli R. Zingg J.M. Azzi A. Circulation. 2000; 102: 82-87Crossref PubMed Scopus (253) Google Scholar). 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Szeto is the and is the on of has the for further and to a in and Szeto and that the brain was in H.H. J. PubMed Google Scholar). The peptides ROS and of the of oxLDL, ligands for CD36 (2.Zhao K. Zhao G.M. Wu D. Soong Y. Birk A.V. Schiller P.W. Szeto H.H. J. Biol. Chem. 2004; 279: 34682-34690Abstract Full Text Full Text PDF PubMed Scopus (606) Google Scholar). the peptides mitochondria and mitochondria and release (2.Zhao K. Zhao G.M. Wu D. Soong Y. Birk A.V. Schiller P.W. Szeto H.H. J. Biol. Chem. 2004; 279: 34682-34690Abstract Full Text Full Text PDF PubMed Scopus (606) Google and apoptosis K. G. S. Szeto H.H. Pharmacol. 2005; PubMed Scopus Google Scholar). These peptide antioxidants are in and infarct following cardiac ischemia reperfusion (2.Zhao K. Zhao G.M. Wu D. Soong Y. Birk A.V. Schiller P.W. Szeto H.H. J. Biol. Chem. 2004; 279: 34682-34690Abstract Full Text Full Text PDF PubMed Scopus (606) Google Scholar, D. Soong Y. Zhao G.M. Szeto H.H. J. 2002; PubMed Scopus Google Scholar, J. J. H. D. J.M. Szeto H. 2005; PubMed Scopus Google Scholar, J. K. Wu D. Soong Y. S. Szeto H.H. Google Scholar). antioxidant by CD36, the study whether the SS31 antioxidant peptide attenuates cerebral ischemia-induced injury and whether the the down-regulation of CD36 expression and SS31 and were by Schiller of as P.W. I. S. G. N.N. C. J. Med. Chem. 2000; 35: PubMed Scopus Google Scholar). LDL was was and and were were on animals were by the and of of C57BL/6 mice were of CD36 mice was Febbraio CD36 mice used in the study were with C57BL/6 mice The for and were to a M. Hajjar D.P. K. Silverstein R.L. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). for were to (1.Cho S. Park E.M. Febbraio M. Anrather J. Park L. Racchumi G. Silverstein R.L. Iadecola C. J. Neurosci. 2005; 25: 2504-2512Crossref PubMed Scopus (169) Google Scholar). mice were with a of and was to the and to the and to a for of cerebral in the of the ischemic MCAO, a was into the advanced into the artery and into the cerebral to the of The was in for and animals that a in during and a of by of reperfusion were in the This to the cerebral cortex and the (1.Cho S. Park E.M. Febbraio M. Anrather J. Park L. Racchumi G. Silverstein R.L. Iadecola C. J. Neurosci. 2005; 25: 2504-2512Crossref PubMed Scopus (169) Google Scholar). was during and animals the of ascorbate and GSH animals were treated with saline SS31 or immediately after In was as a free radical (2.Zhao K. Zhao G.M. Wu D. Soong Y. Birk A.V. Schiller P.W. Szeto H.H. J. Biol. Chem. 2004; 279: 34682-34690Abstract Full Text Full Text PDF PubMed Scopus (606) Google Scholar). a in GSH and but not and in studies we SS31. of infarct or SS31 or of was immediately after reperfusion and and The was is a ROS production and CD36 expression in post-ischemic brain (1.Cho S. Park E.M. Febbraio M. Anrather J. Park L. Racchumi G. Silverstein R.L. Iadecola C. J. Neurosci. 2005; 25: 2504-2512Crossref PubMed Scopus (169) Google Scholar, A. Anrather J. M. Iadecola C. J. Google Scholar). The of SS31 used in the study was on the used in protection ischemia J. J. H. D. J.M. Szeto H. 2005; PubMed Scopus Google and in a of S. M. M. A. G. Szeto H.H. J. Neurochem. PubMed Scopus Google Scholar). were after were and in a as (1.Cho S. Park E.M. Febbraio M. Anrather J. Park L. Racchumi G. Silverstein R.L. Iadecola C. J. Neurosci. 2005; 25: 2504-2512Crossref PubMed Scopus (169) Google Scholar). were and with volume was and the of was the Wu G. Khan M. 1993; PubMed Scopus Google Scholar). tissue cortex and of ipsilateral and were to ischemia and and after of transient of and cortex and were into in liquid and of redox tissue was in of a with a to a a of was to of metaphosphoric and the was for on for of the were for of redox of the ascorbate and the and were measured a with J. PubMed Scopus Google Scholar, J.M. A.J. J. Neurochem. 2005; PubMed Scopus Google Scholar). The the were a and with a of and a of was used the and a was and to and with a was used to The were and were among were of redox and were and were as were in of and was by a were after of of The peritoneal was and of saline was The was and the was was the is were by for were in a for CD36 for CD36 or for foam cell and with macrophage The cells were with treated with oxLDL with or SS31 or for were used for CD36 expression and foam cell of CD36 were with was brain tissue or or was and the to the and for CD36 and were as for expression was used as for of The reaction was and to by the were in a volume of and were for by of and were as The were by were and in a and for with macrophage to a M. Hajjar D.P. S.L. K. Silverstein R.L. J. Clin. Investig. 2000; PubMed Scopus Google Scholar). The cells were treated with oxLDL with or SS31 for were in of with The was for and the was CD36 expression was to the (1.Cho S. Park E.M. Febbraio M. Anrather J. Park L. Racchumi G. Silverstein R.L. Iadecola C. J. Neurosci. 2005; 25: 2504-2512Crossref PubMed Scopus (169) Google Scholar). were on a and to were treated for in and and with CD36 by mouse was were and the were a were in in macrophage were treated with oxLDL with or SS31 for were with PBS, in for with for in a with PBS, and The were the foam cell were that within by were were expressed as and GSH and GSH were in the post-ischemic cortex and striatum. were in the after in the ischemic were significantly in the by after ischemia and By contrast, the of ascorbate and the major intracellular antioxidants in were in the ipsilateral within a of reperfusion depletion was in cortex and by of The depletion was a the infarct is These that biochemical changes status with but GSH Depletion in the of SS31 on redox and GSH were after ischemia in mice that were treated with saline SS31 or reperfusion The were expressed as and depletion and with the was in and ascorbate among and not By contrast, ischemia-induced GSH depletion in the ipsilateral cortex was significantly attenuated in animals with that of the The of ipsilateral GSH depletion in mice was not significantly that of mice The that SS31 in antioxidant status and ischemia-induced depletion of GSH in the of peptides on ischemia-induced and GSH C57BL/6 mice were subjected to of and treated with saline SS31 or peptide immediately after were of animals of animals of animals animals in a with SS31 whether the in GSH depletion by SS31 is associated with were subjected to of and treated with or SS31 and and and after were after and high treatment with SS31 in and in infarct volume The of cerebral during among were SS31 SS31 In addition, reperfusion was not among SS31 SS31 the that SS31 during the reperfusion SS31 in CD36 has been to ischemia-induced tissue injury (1.Cho S. Park E.M. Febbraio M. Anrather J. Park L. Racchumi G. Silverstein R.L. Iadecola C. J. Neurosci. 2005; 25: 2504-2512Crossref PubMed Scopus (169) Google Scholar). investigate whether SS31 by CD36 GSH were measured after ischemia in CD36 mice treated with either or SS31 C57BL/6 mice in SS31 effect on ischemia-induced GSH depletion in CD36 mice SS31 treatment not infarct volume in CD36 mice of of SS31 in CD36 mice that in C57BL/6 mice may be inhibition of CD36-mediated with SS31 in CD36 investigate the effect of SS31 on CD36 expression in we CD36 expression in the ischemic with the CD36 expression was significantly in the ipsilateral after ischemia SS31 treatment in a but in CD36 we were to a in CD36 expression and not This may be of the that CD36 is expressed in microglia and macrophages (1.Cho S. Park E.M. Febbraio M. Anrather J. Park L. Racchumi G. Silverstein R.L. Iadecola C. J. Neurosci. 2005; 25: 2504-2512Crossref PubMed Scopus (169) Google and may be to of CD36 expression that in of in the SS31 effect on CD36 we the the effect of SS31 in and CD36 expression in analysis within mice revealed that CD36 in after ischemia were significantly with infarct a and reduced CD36 by SS31 SS31 oxLDL-induced CD36 and in the effect of SS31 on inflammatory oxLDL-induced CD36 expression and were in in the and of SS31. with treated with oxLDL for and CD36 by and with SS31 in high and low for significantly attenuated oxLDL-induced CD36 expression In addition, oxLDL-induced CD36 expression was also attenuated by SS31 treatment In to whether the reduced CD36 expression by SS31 in lipid uptake into MPM, in vitro foam cell formation was with with oxLDL for in foam cell was significantly attenuated by SS31 the indicate that SS31 attenuates oxLDL-induced CD36 expression and in of SS31 on foam cell formation in MPM. were and for as saline oxLDL oxLDL SS31 The were with for of that are or the of were in that treatment with oxLDL foam cell formation by is significantly attenuated by with SS31. with Oxidative stress has been implicated in injury. The of antioxidant and the of of the antioxidant into the of tissue injury. The study the of a cell-permeable antioxidant on cerebral injury during reperfusion after transient cerebral that the of SS31 is through inhibition of CD36 of the and status during In the of redox status triggered by stress was by the of and GSH and ascorbate were in the ipsilateral with in GSH to ascorbate depletion may be associated with of ascorbate in mice with high expression of the in and in brain M. T. A. C. K. O. J. Neurochem. 2001; PubMed Scopus Google Scholar). not GSH depletion in brain a on redox during ischemic injury. depletion of antioxidants in mice may cell These that GSH and ascorbate are biochemical markers that changes in redox In the SS31 significantly attenuated ischemia-induced GSH depletion and to redox in the postischemic but not in the and significantly reduced infarct the the of the of antioxidants during reperfusion may be in the The of ischemia-induced GSH depletion in the cortex is with the of SS31 to ROS I. Wu H. G. J. Pathol. 2004; Full Text Full Text PDF PubMed Scopus Google Scholar). studies that SS31 the membrane and inhibits induced by and (2.Zhao K. Zhao G.M. Wu D. Soong Y. Birk A.V. Schiller P.W. Szeto H.H. J. Biol. Chem. 2004; 279: 34682-34690Abstract Full Text Full Text PDF PubMed Scopus (606) Google Scholar). SS31 and radical and in vitro (2.Zhao K. Zhao G.M. Wu D. Soong Y. Birk A.V. Schiller P.W. Szeto H.H. J. Biol. Chem. 2004; 279: 34682-34690Abstract Full Text Full Text PDF PubMed Scopus (606) Google Scholar, H.H. J. PubMed Google Scholar). be by to or with to S. J.M. J. 2004; PubMed Scopus Google Scholar). The of for in (2.Zhao K. Zhao G.M. Wu D. Soong Y. Birk A.V. Schiller P.W. Szeto H.H. J. Biol. Chem. 2004; 279: 34682-34690Abstract Full Text Full Text PDF PubMed Scopus (606) Google Scholar, H.H. J. PubMed Google Scholar). of reperfusion not a effect on GSH ischemia is associated with a local inflammatory reaction that to tissue In activated and release and demonstrated that CD36 expression is in in the post-ischemic brain and that CD36-mediated ROS production is in ischemia-induced brain injury (1.Cho S. Park E.M. Febbraio M. Anrather J. Park L. Racchumi G. Silverstein R.L. Iadecola C. J. Neurosci. 2005; 25: 2504-2512Crossref PubMed Scopus (169) Google Scholar). The study also that CD36 mice were cerebral ischemia by significantly reduced infarct volume (1.Cho S. Park E.M. Febbraio M. Anrather J. Park L. Racchumi G. Silverstein R.L. Iadecola C. J. Neurosci. 2005; 25: 2504-2512Crossref PubMed Scopus (169) Google Scholar). cerebral CD36 including long chain fatty acids, oxidized and T. N. T. J. 2003; PubMed Google Scholar, I. Wu H. G. J. Pathol. 2004; Full Text Full Text PDF PubMed Scopus Google Scholar, M. K. H. S. J. Neurosurg. 2003; PubMed Scopus Google Scholar, J.M. Res. 2003; PubMed Scopus Google Scholar, T. S. Y. T. T. M. R. N. S. J. Neurochir. (Wien). 2001; PubMed Scopus Google during SS31 not further ischemia-induced GSH depletion in cortex as as infarct volume in CD36 mice the of of SS31 on CD36 mice in the study that the of SS31 in C57BL/6 mice inhibition of CD36 the study that a protection in CD36 mice (1.Cho S. Park E.M. Febbraio M. Anrather J. Park L. Racchumi G. Silverstein R.L. Iadecola C. J. Neurosci. 2005; 25: 2504-2512Crossref PubMed Scopus (169) Google a in infarct volume in CD36 mice was In the study infarct volume was CD36 and were by to C57BL/6 and By contrast, the of SS31 was in C57BL/6 In addition, and and ischemic to in current study may to a in infarct volume in the CD36 mice with C57BL/6 mice the study not the as to SS31 attenuates CD36-mediated injury in cerebral that CD36 expression is in the postischemic brain (1.Cho S. Park E.M. Febbraio M. Anrather J. Park L. Racchumi G. Silverstein R.L. Iadecola C. J. Neurosci. 2005; 25: 2504-2512Crossref PubMed Scopus (169) Google Scholar). studies that oxidative stress CD36 expression and oxLDL uptake and that antioxidants reduce expression and (15.Fuhrman B. Volkova N. Aviram M. Atherosclerosis. 2002; 161: 307-316Abstract Full Text Full Text PDF PubMed Scopus (125) Google Scholar, 16.Venugopal S.K. Devaraj S. Jialal I. Atherosclerosis. 2004; 175: 213-220Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar, 17.Ricciarelli R. Zingg J.M. Azzi A. Circulation. 2000; 102: 82-87Crossref PubMed Scopus (253) Google Scholar, M. K. H. S. J. Neurosurg. 2003; PubMed Scopus Google Scholar). In the current CD36 expression was significantly in ischemic brain after MCAO, that SS31 in by inhibition of CD36 we were to a in CD36 in the ischemic CD36 expression in in post-ischemic brain (1.Cho S. Park E.M. Febbraio M. Anrather J. Park L. Racchumi G. Silverstein R.L. Iadecola C. J. Neurosci. 2005; 25: 2504-2512Crossref PubMed Scopus (169) Google is that the of may not be to a in a of cells in infarct we CD36 in ischemic mice, infarct was with CD36 in the that SS31 attenuates CD36 The that SS31 reduces CD36 expression is further by in vitro study that SS31 reduce oxLDL-induced CD36 expression and in and SS31 treatment may also during In to CD36 SS31 reduce by LDL as demonstrated in a study (2.Zhao K. Zhao G.M. Wu D. Soong Y. Birk A.V. Schiller P.W. Szeto H.H. J. Biol. Chem. 2004; 279: 34682-34690Abstract Full Text Full Text PDF PubMed Scopus (606) Google Scholar). The further CD36 and expression J. Hajjar D.P. Febbraio M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google in a L. H. Full Text Full Text PDF PubMed Scopus Google Scholar, L. Full Text Full Text PDF PubMed Scopus Google Scholar, J. Han J. Silverstein R.L. Hajjar D.P. J. Res. 2000; Full Text Full Text PDF PubMed Google and CD36 in a that further oxLDL SS31 either the in reduced oxLDL or the receptor by CD36 the be CD36 protective effect of SS31 in mice CD36 receptor are with the of the of the in these SS31 may on a in the CD36 The mediates ROS production in in response to oxidative stress (1.Cho S. Park E.M. Febbraio M. Anrather J. Park L. Racchumi G. Silverstein R.L. Iadecola C. J. Neurosci. 2005; 25: 2504-2512Crossref PubMed Scopus (169) Google Scholar, J. C. Silverstein J.B. J. Pathol. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar, H. J. El Khoury J. Silverstein J. Exp. Med. PubMed Scopus Google Scholar). The of ROS are activation of or the SS31 ROS, to ROS be of the that SS31 within the membrane (2.Zhao K. Zhao G.M. Wu D. Soong Y. Birk A.V. Schiller P.W. Szeto H.H. J. Biol. Chem. 2004; 279: 34682-34690Abstract Full Text Full Text PDF PubMed Scopus (606) Google Scholar). CD36 is in mitochondria skeletal and expression is by skeletal S.E. Tandon N.N. Woldegiorgis G. Luiken J.J. Glatz J.F. Bonen A. J. Biol. Chem. 2004; 279: 36235-36241Abstract Full Text Full Text PDF PubMed Scopus (209) Google Scholar, V. C.R. G.J. Tandon N.N. Glatz J.F. Luiken J.J. Bonen A. J. PubMed Scopus (115) Google Scholar). CD36 is also as fatty and is in uptake and of long chain fatty It has been that free fatty by ROS production in postischemic S. C. R. D. A. L. PubMed Scopus Google Scholar). In of stroke concentrations are elevated and the is associated with a outcome in stroke J.M. Res. 2003; PubMed Scopus Google Scholar, J.M. J. Neurosurg. 2002; PubMed Scopus (40) Google Scholar). The of CD36 in brain cells or whether expression in mitochondria is by or oxidative stress is not role for SS31 on CD36 with uptake and the redox through ROS to be The of CD36, with the to into the for fatty may role of CD36 in is and activated the to the that inhibition of ischemia-induced activation in stroke H. J. J. Biol. Chem. 2005; Full Text Full Text PDF PubMed Scopus Google activation is to production to for that activation CD36 expression in cardiac A. I. Coort S.L. J. Tandon N.N. Glatz J.F. Luiken J.J. Bonen A. PubMed Scopus Google Scholar). of CD36 the intracellular to the plasma membrane for uptake of into cells and fatty A. J. J. Tandon N.N. Bonen A. PubMed Scopus Google Scholar). Further studies on the of SS31 on of uptake and fatty be In the study that a pro-oxidative status in the novel cell-permeable antioxidant is in oxidative stress and ischemia-induced injury. The effect of SS31 antioxidant peptide the of CD36 by expression and through inflammatory cells in the injury site. The study that CD36 by novel class of antioxidants be used as a strategy to reduce acute injury.
Cho et al. (Tue,) studied this question.