S-nitrosylation of PTEN Invovled in ischemic brain injury in rat hippocampal CA1 region.
The tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10) is not only a protein, but also a lipid phosphatase that can negatively regulate the serine/threonine kinase Akt. It has been reported that PTEN can be regulated by means of phosphorylation. However, whether PTEN can be regulated by another post-translational protein modification (S-nitrosylation) was not fully elucidated. In this study, we investigated the S-nitrosylation of PTEN during transient cerebral ischemia/reperfusion in rat hippocampus. Transient brain ischemia was induced by the four-vessel occlusion in Sprague-Dawley rats. Our data show that S-nitrosylation of PTEN was increased significantly after 12 h of reperfusion compared with sham control. Pretreatment with the inhibitor of nNOS (7-NI) and the inhibitor of iNOS could inhibit PTEN's activity and decrease S-nitrosylation of PTEN. Taken together, these results indicate that nitric oxide could regulate PTEN's activity via S-nitrosylation during transient global ischemia in rat hippocampus.
Pei
Dong-Sheng
DS
Laboratory of Biological Cancer Therapy, Xuzhou Medical College, 84 West Huai-hai Road, 221002 Xuzhou, Jiangsu, People's Republic of China. dspei@xzmc.edu.cn
Sun
Ya-Feng
YF
Song
Yuan-Jian
YJ
D000818:Animals; D015153:Blotting, Western; D002545:Brain Ischemia / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D047468:Immunoprecipitation; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors; D009603:Nitroso Compounds / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism
D004791:Enzyme Inhibitors; D007191:Indazoles; D009603:Nitroso Compounds; D052248:Nitric Oxide Synthase Type I; D051059:PTEN Phosphohydrolase; C487216:Pten protein, rat; C080122:7-nitroindazole