Neuroprotective effect of resveratrol against brain ischemia reperfusion injury in rats entails reduction of DJ-1 protein expression and activation of PI3K/Akt/GSK3b survival pathway.
In the current study, we aimed to investigate the mechanistic role of DJ-1/PI3K/Akt survival pathway in ischemia/reperfusion (I/R) induced cerebral damage and to investigate if the resveratrol (RES) mediates its ischemic neuroptotection through this pathway. RES administration to Sham rats boosted glutathione level and superoxide dismutase activity and downregulated inducible nitric oxide synthase expression without affecting redox levels of DJ-1 forms or components of PI3K/Akt pathway including PTEN, p-Akt or p/p-GSK3b. However, RES pre-administration to I/R rats reduced infarction area, oxidative stress, inflammation and apoptosis. Concomitantly, RES ameliorated the decreased levels of oxidized forms of DJ-1 and enhancing its reduction, increased the nuclear protein expression of Nfr-2 and led to activation of PI3K/Akt survival pathway. In conclusion, overoxidation of DJ-1 is a major factor that contributes to post-I/R cerebral damage and its reduction by RES could explain the neuroprotection offered by RES.
a Department of Medical Biochemistry , Faculty of Medicine, Tanta University , Tanta , Egypt.|b Department of Medical Biochemistry , College of Medicine, King Khalid University , Abha , Saudi Arabia.
Ghada A
GA
Abdel-Aleem
c Department of Medical Physiology , Faculty of Medicine, Cairo University , Cairo , Egypt.|d Department of Medical Physiology , College of Medicine, King Khalid University , Abha , Saudi Arabia.
Eman F
EF
Khaleel
d Department of Medical Physiology , College of Medicine, King Khalid University , Abha , Saudi Arabia.|e Department of Medical Physiology , Faculty of Medicine, Assiut University , Assiut , Egypt.
Dalia G
DG
Mostafa
f Department of Histopathology , College of Medical Laboratory Technology, University of Science and Technology , Khartoum , Sudan , and.|g Department of Pathology , College of Medicine, King Khalid University , Abha , Saudi Arabia.
Lydia K
LK
Elberier
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000071679:Glycogen Synthase Kinase 3 beta / Q000235:genetics / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D000071617:Protein Deglycase DJ-1 / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*
D000975:Antioxidants; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D013267:Stilbenes; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; C404267:PARK7 protein, rat; D000071617:Protein Deglycase DJ-1; D000077185:Resveratrol
DJ-1; Nrf-2; PI3K/Akt; Resveratrol; brain; ischemia reperfusion; oxidative stress