Gene Expression Profiles of Cultured Rat Cardiomyocytes (H_9C_2 Cells) in Response to Arsenic Trioxide at Subcytotoxic Level and Oxidative Stress
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概要
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Epidemiologic studies have suggested a close correlation between arsenic exposure and cardiovascular disease. In mechanism studies of heart disease and arsenic exposure, blood vessels, vascular smooth muscle cells, and endot-helial cells of the artery have long been thought to be the primary targets in arsenic exposure but there are only a few studies on cardiomyocytes. In this study, to predict more diverse responses of cardiomyocytes to arsenic exposure in the development of heart failure, gene expression profiles of cultured rat cardiomyocytes (H_9C_2 cell line) were evaluated using the rat whole-genome microarray when a subcytotoxic level of arsenic trioxide was treated. After 24 hr of arsenic 0.5 ppm exposure (As_2O_3 was used), 405 genes were up-regulated including heme oxygenase-1, and 499 genes were down-regulated including fibroblast growth factor. With the subcytotoxic dose of As_2O_3, oxidative stress was generated without cell death, and the transcription of stress-related genes such as heme oxygenase-1, glutathione S-transferase, metallothionein, and catalase were significantly increased. Direct measurement of reactive oxygen species using fluorescent dye showed that arsenic caused oxidative stress at the subcytotoxic level. Although no direct comparison was made among different types of cells in this study, it appears that arsenic can cause physiologic adverse reactions at a relatively low level in cardiomyocytes and that cardiomyocytes are also one of the vulnerable targets of heart failure by arsenic compounds.
- 公益社団法人日本薬学会の論文
- 2006-10-01
著者
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PARK Eun-Jung
College of Pharmacy, Ewha Womans University
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Park Eun-jung
Coll. Of Pharmacy Dongduk Women's Univ.
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Park Kwangsik
College Of Pharmacy Dongduk Women's University
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Park Eun-jung
College Of Pharmacy Dongduk Women's University
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