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标题：Phthalate Exposure Changes the Metabolic Profile of Cardiac Muscle Cells
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作者：Nikki Gillum Posnack ; Luther M. Swift ; Matthew W. Kay 等
期刊名称：Environmental Health Perspectives
印刷版ISSN：0091-6765
电子版ISSN：1552-9924
出版年度：2012
卷号：120
期号：9
页码：1243-1251
DOI：10.1289/ehp.1205056
出版社：OCR Subscription Services Inc
摘要：Ba c k g r o u n d: P hthalates are common plasticizers present in medical-grade plastics and other everyday products. They can also act as endocrine-disrupting chemicals and have been linked to the rise in metabolic disorders. However, the effect of phthalates on cardiac metabolism remains largely unknown.oB j e c t i v e s: We examined the effect of di(2-ethylhexyl)phthalate (DEHP) on the metabolic profile of cardio myocytes because alterations in metabolic processes can lead to cell dysfunction.Me t h o d s: Neonatal rat cardiomyocytes were treated with DEHP at a concentration and duration comparable to clinical exposure (50–100 μg/mL, 72 hr). We assessed the effect of DEHP on gene expression using microarray analysis. Physiological responses were examined via fatty acid utiliza-tion, oxygen consumption, mitochondrial mass, and Western blot analysis.re s u l t s: Exposure to DEHP led to up-regulation of genes associated with fatty acid transport, esterification, mitochondrial import, and β-oxidation. The functional outcome was an increase in myo cyte fatty acid–substrate utilization, oxygen consumption, mitochondrial mass, PPARα(peroxi-some proliferator-activated receptor α) protein expression, and extra cellular acidosis. Treatment with a PPARαagonist (Wy-14643) only partially mimicked the effects observed in DEHP-treated cells.co n c l u s i o n s: Data suggest that DEHP exposure results in metabolic remodeling of cardio-myocytes, whereby cardiac cells increase their dependence on fatty acids for energy production. This fuel switch may be regulated at both the gene expression and post transcription levels. Our findings have important clinical implications because chronic dependence on fatty acids is associated with an accumulation in lipid inter mediates, lactate, protons, and reactive oxygen species. This dependence can sensitize the heart to ischemic injury and ventricular dysfunction
关键词：di(2-ethylhexyl)phthalate; cardiomyocyte; fatty acid metabolism; microarray