A novel cell-permeable antioxidant peptide, SS31, attenuates ischemic brain injury by down-regulating CD36.

Cho S, Szeto HH, Kim E, Kim H, Tolhurst AT, Pinto JT

The Journal of biological chemistry18 Dec 2006Cited by 141 (Europe PMC)

PMID17178711DOI10.1074/jbc.m609388200PepBankPUB-17178711

Summary

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). 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). 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.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study7

7 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
In mice with transient MCAO, SS31 given immediately after reperfusion significantly attenuated ischemia-induced glutathione depletion in the cortex.
In plain wordsIn mice with a stroke-like injury, SS31 given right after blood flow returned reduced the loss of the antioxidant glutathione in the cortex.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseIschemia-induced glutathione depletion in cortex
Study
mousen: not reported in source
Transient middle cerebral artery occlusion (MCAO) in C57BL/6 mice
Comparator
Saline
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Treating mice with SS31 immediately after reperfusion significantly attenuated ischemia-induced GSH depletion in the cortex
1 context sentence(design, population, supporting numbers)
Summary · context
C57BL/6 mice were subjected to transient middle cerebral artery occlusion (MCAO).
Show in the study text Report a problemFND-1717871101
02AnimalAnimal study (in vivo)Efficacy outcome
In mice with transient MCAO, SS31 given immediately after reperfusion reduced infarct size.
In plain wordsIn mice with a stroke-like injury, SS31 given right after blood flow returned reduced the size of the brain damage.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseInfarct size
Study
mousen: not reported in source
Transient middle cerebral artery occlusion (MCAO) in C57BL/6 mice
Comparator
Saline
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Treating mice with SS31 immediately after reperfusion significantly attenuated ischemia-induced GSH depletion in the cortex and reduced infarct size.
Show in the study text Report a problemFND-1717871102
03AnimalAnimal study (in vivo)Mechanism
In CD36 knock-out mice with MCAO, the protective effect of SS31 was absent, indicating that SS31 acts through inhibition of CD36.
In plain wordsIn mice lacking CD36, SS31 no longer protected the brain after a stroke-like injury, suggesting it works through CD36.
Peptide
Elamipretide (SS-31)
Outcome
No significant changeProtective effect of SS31 in CD36 knock-out mice
Study
mousen: not reported in source
MCAO in CD36 knock-out mice
Comparator
Wild-type mice
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
By contrast, the protective effect of SS31 was absent in CD36 knock-out mice, indicating that SS31 is acting through inhibition of CD36.
1 context sentence(design, population, supporting numbers)
Summary · context
C57BL/6 mice were subjected to transient middle cerebral artery occlusion (MCAO).
Show in the study text Report a problemFND-1717871103
04AnimalAnimal study (in vivo)Mechanism
In C57BL/6 mice with MCAO, SS31 treatment reduced CD36 expression in postischemic brain.
In plain wordsIn mice with a stroke-like injury, SS31 lowered levels of the CD36 receptor in the injured brain.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseCD36 expression in postischemic brain
Study
mousen: not reported in source
Transient middle cerebral artery occlusion (MCAO) in C57BL/6 mice
Comparator
Saline
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Treating C57BL/6 mice with SS31 reduced CD36 expression in postischemic brain
1 context sentence(design, population, supporting numbers)
Summary · context
C57BL/6 mice were subjected to transient middle cerebral artery occlusion (MCAO).
Show in the study text Report a problemFND-1717871104
05AnimalAnimal study (in vivo)Mechanism
In C57BL/6 mice, SS31 treatment reduced CD36 expression in mouse peritoneal macrophages.
In plain wordsIn mice, SS31 treatment lowered levels of the CD36 receptor in immune cells from the abdomen.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseCD36 expression in peritoneal macrophages (in vivo treatment)
Study
mousen: not reported in source
Mouse peritoneal macrophages from SS31-treated C57BL/6 mice
Comparator
Saline
Outcome group
Receptor activity and mechanism · Immune and inflammation
Studied dose
Dose not stated
Source sentences
Summary
Treating C57BL/6 mice with SS31 reduced CD36 expression in postischemic brain and mouse peritoneal macrophages (MPM).
Show in the study text Report a problemFND-1717871105
06LabIn vitro (cells)Mechanism
In mouse peritoneal macrophages, SS31 attenuated oxLDL-induced CD36 expression.
In plain wordsIn mouse immune cells in the lab, SS31 reduced the rise in CD36 caused by oxidized LDL.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseoxLDL-induced CD36 expression in macrophages
Study
mousen: not reported in source
Mouse peritoneal macrophages (MPM)
Comparator
oxLDL alone
Outcome group
Receptor activity and mechanism · Immune and inflammation
Studied dose
Dose not stated
Source sentences
Summary
SS31 attenuated oxLDL-induced CD36 expression and foam cell formation in MPM.
Show in the study text Report a problemFND-1717871106
07LabIn vitro (cells)Mechanism
In mouse peritoneal macrophages, SS31 attenuated oxLDL-induced foam cell formation.
In plain wordsIn mouse immune cells in the lab, SS31 reduced the formation of fat-laden foam cells triggered by oxidized LDL.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseoxLDL-induced foam cell formation in macrophages
Study
mousen: not reported in source
Mouse peritoneal macrophages (MPM)
Comparator
oxLDL alone
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
Dose not stated
Source sentences
Summary
SS31 attenuated oxLDL-induced CD36 expression and foam cell formation in MPM.
Show in the study text Report a problemFND-1717871107

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
10 Oct 2026, 08:19 UTC
Study results updated
Version 1
9 Oct 2026, 02:47 UTC
First added · source update from Europe PMC

Subjects

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