Ariamycin Effects Endothelin-1 Expression of Heart

• Main Authors: Wen-Hsuan Fong, 馮婉萱
• Other Authors: Neng-Lang Shih
• Format: Others
• Language: zh-TW
• Online Access: http://ndltd.ncl.edu.tw/handle/14823504937632400411

碩士 === 國立高雄大學 === 生物科技研究所 === 93 === The current study investigated the effects of adriamycin on ET-1 regulation in the heart. Adriamycin(Doxorubicin), a quinone-containing anthracycline antibiotics, is one of the most typical antineoplastic drugs and is in routine clinical use as therapeutic agents; the development of severe cardiac toxicity in human limits administration exceeding an accumulated dose of approximately 550mg/m2 . Although the mechanism of adriamycin-induced cardiomyopathy is multifactorial, increased oxidative stress due to overproduction of free radicals and antioxidant-deficit play an important role. In addition, recent studies are reported that endothelin-1 (ET-1) has the potential to be the maker of DOX induced caidac damage. Yamashita et al. (1994) and Yamashita et al. (1995) reported that they found that plasma ET-1 level increased in patients with lung cancer who receipted DOX treatments and have the progression of heart failure. Sayed-Ahmed et al. (2001) also reported that plasma ET-1 level increased in rat treated with DOX but there were reversed results. So we are interesting in the ET-1 expression patterns and molecular mechanisms of myocytes and non-myocytes treated with DOX. In our previous studies, we found that ROS can induce ET-1 expression in fibroblasts and endothelial cells. Then we are also interesting in the role of ROS in myocytes and non-myocytes treated with DOX. In this present study, we found that DOX could induce ET-1 mRNA expression and ET-1 secretion of myocytes and there exited a time lag. In non-myocytes, DOX inhibited ET-1 mRNA expression before 6 hours but ET-1 secretion rapidly increased after stimulated by DOX. Following intracellular ROS assay revealed that DOX induced ROS formation then with the consequence of ET-1 promoter activation in myocytes. In non-myocytes, DOX treated non-myocytes had similar ROS level with control. It’s clear that DOX can stimulate ET-1 expression in myocytes by activating ET-1 promoter through ROS mediated signal pathway. On the other hand, DOX may stimulate ET-1 secretion through the storage and transport system in non-myocytes .