| Summary: | 碩士 === 臺北醫學大學 === 醫學科學研究所 === 97 === Iron deposition usually occurs in Thalassemia or alcoholic liver injury patients, of which the process of iron transportation or utilization is suppressed. Overloaded iron in cells causes oxidative injury and mitochondria dysfunction. It elicits inflammatory response and the activation of apoptotic pathway in various cell types, thereby leading to cell death and tissue damage. Many studies have shown that heme oxygenase-1 (HO-1) and cyclooxygenase-2 (COX-2) have important anti-inflammatory and anti- apoptotic roles in various tissues. Induction of these enzymes has been shown to protect various cells from oxidative or inflammatory insults. In this study, we demonstrated that hepatocytes treated with adiponectin caused significant increases in HO-1/COX-2 RNAs and protein expressions. It was further increased by approximately 6.5 fold in cells transfected with pcDNA3.1-PPARα. Conversely, PPARα knock down reversed APN-mediated HO-1/COX-2 induction, suggesting that induction of HO-1/COX-2 is dependent on PPARα. Additionally, adiponectin mediated HO-1/COX-2 induction is essential for the elimination of iron-mediated apoptosis and inflammation in hepatocytes. Using pharmaceutical inhibitors, we further demonstrated that the anti-apoptotic effect of HO-1 and anti-inflammatory effect of COX-2 synergistically contributed to the protection of adiponectin against iron-mediated hepatic injury. Taken together, we illustrated the effects and molecular mechanism of adiponectin mediated PPARα activation, in a concomitant induction of HO-1/COX-2 in the protection of hepatic apoptosis in vitro.
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