Cytoprotective effects of selenium on cadmium-induced LLC-PK1 cells apoptosis by activating JNK pathway.
Extensive studies have indicated that the apoptosis pathway appears to be associated with intracellular reactive oxygen species (ROS) production in cadmium-induced nephrotoxicity, however, the precise cellular mechanism remains unclear. The purpose of this study was to determine the relationships between the activation of phosphorylated c-jun N-terminal kinase (JNK) and cadmium-induced apoptosis, and assess the possible cytoprotective mechanism of selenium. Our study clearly revealed cadmium treatment caused apoptosis in LLC-PK1 cells, which was partially suppressed by pretreatment with selenium, an antioxidant nutrient. Further studies found the phosphorylation of JNK kinase increased with exposure to cadmium for 3 h, even remained elevated at 9 h in the time course study, and the activation of phosphorylated JNK was detected in a dose-dependent manner. In addition, a concomitant time-dependent increase in caspase-3 activities was observed by cadmium treatment. During the process, selenium played the same role as N-acetyl-L-cysteine (NAC), a free radical scavenger. Pretreatment of cells with selenium partially suppressed of the phosphorylation of JNK, coupled with caspase-3 activation involved in cadmium-induced apoptosis. In conclusion, our studies provided a molecular linkage between the phosphorylation of JNK and cadmium-induced LLC-PK1 cells apoptosis, and demonstrated selenium also contributed a potentially protection to prevent cadmium-cytotoxicity.
Liu
Yan
Y
Department of Nutrition and Food Hygiene, Nanjing Medical University, Nanjing 210029, People's Republic of China.
Zhang
Shi-Ping
SP
Cai
Yun-Qing
YQ
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006690:Bisbenzimidazole; D015153:Blotting, Western; D002104:Cadmium / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D053148:Caspase 3 / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018374:LLC-PK1 Cells; D010766:Phosphorylation; D012643:Selenium / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013552:Swine
D000975:Antioxidants; D002104:Cadmium; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3; D012643:Selenium; D006690:Bisbenzimidazole