Protective effect of selenite on renal ischemia/reperfusion injury through inhibiting ASK1-MKK3-p38 signal pathway.
Previous studies have reported that selenite, a known antioxidant, protects brain against ischemia/reperfusion injury, which is mediated by oxidative stress. The aim of this study was to investigate whether selenite can protect kidney against ischemic injury by reducing activation of the apoptosis signal regulating kinase 1 (ASK1)/mitogen-activated protein kinase kinase 3 (MKK3)/p38 mitogen-activated protein kinase signaling pathway. The activation and expression of ASK1, MKK3, p38, caspase 3 and cleaved PARP were analyzed by Western blot. Apoptosis of renal tubular epithelial cells was assessed by the terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling method. Malondialdehyde (MDA) levels were measured by the thiobarbituric acid reaction. Blood serum creatinine and blood urea nitrogen level were measured with an Olympus automatic multi-analyzer. We found that selenite attenuated significantly ASK1, MKK3, and p38 phosphorylation at 3 h after renal ischemia. Furthermore, selenite decreased significantly renal epithelial tubular cell apoptosis. In addition, selenite reduced the MDA level. These findings suggest that the protective action of selenite on ischemia renal injury is associated closely with reducing activation of the ASK1-MKK3-p38 signal pathway.
Wang
Yan
Y
Department of Pharmacy, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China. xzwyjhx@163.com
Ji
Huai-Xue
HX
Zheng
Jun-Nian
JN
Pei
Dong-Sheng
DS
Hu
Shu-Qun
SQ
Qiu
Shu-Ling
SL
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D048371:MAP Kinase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D048848:MAP Kinase Kinase Kinase 5 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D018038:Sodium Selenite / Q000494:pharmacology / Q000627:therapeutic use*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000975:Antioxidants; D011065:Poly(ADP-ribose) Polymerases; D048051:p38 Mitogen-Activated Protein Kinases; D048848:MAP Kinase Kinase Kinase 5; D048371:MAP Kinase Kinase 3; D053148:Caspase 3; D018038:Sodium Selenite