Protective effect of protein kinase C and mitogen-activated protein kinases and its mechanism in liver ischemic preconditioning / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the protective effects of protein kinase C (PKC) and mitogen-activated protein kinases (MAPKs) their and mechanisms in liver ischemic preconditioning.</p><p><b>METHODS</b>In rat models of liver ischemia-reperfusion (IR) and ischemic preconditioning (IP), the liver function was evaluated by examining serum alanine aminotransferase and aspartate aminotransferase levels, and the morphological changes of the liver cells were observed under microscope. PKC activator phorbol 12-myristate 13-acetate(PMA) and inhibitor chelerythrine(CHE), as well as MEK inhibitor PD98059, were utilized to analyze the phosphorylation of PKC and P44/42 MAPKs.</p><p><b>RESULTS</b>Compared with the control rats, the liver function was best protected in rats of IP group, but not in those of IP group with PD98059 or CHE treatment. The rats in IR group showed improved liver function after PMA treatment. Similarly, the phosphorylation of PKC and P44/42 MAPKs was correlated with the liver function, and highly enhanced PKC and P44/42 MAPKs activity was observed in IP and IR+PMA groups, but decreased activity in IR and IP+CHE groups.</p><p><b>CONCLUSION</b>Phosphorylation of PKC and MAPKs plays a pivotal role in the preservation of the hepatocytes during IP.</p>