Distinct transcriptional regulation of long-chain acyl-CoA synthetase isoforms and cytosolic thioesterase 1 in the rodent heart by fatty acids and insulin
Distinct transcriptional regulation of long-chain acyl-CoA synthetase isoforms and cytosolic thioesterase 1 in the rodent heart by fatty acids and insulin
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DOI：
10.1152/ajpheart.01344.2005
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发表时间：
2006-06-01
影响因子：
4.8
通讯作者：
Young, Martin E.
中科院分区：
文献类型：
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作者：
Durgan, David J.;Smith, Justin K.;Young, Martin E.
负责将长链脂肪酸(LCFA)引导到氧化途径而不是非氧化途径的分子机制(S)在心脏中知之甚少。细胞内的低分子脂肪酸在一系列长链脂肪酰基-辅酶A合成酶(ACSLs)的作用下转化为长链脂肪酰基-辅酶A(LCFA-COAS)。胞质硫酯酶1(CTE1)可将胞质LCFA-COA水解为低碳链脂肪酸，从而产生一个潜在的无用循环，以牺牲ATP的利用率为代价。我们假设，在生理和病理生理条件下，ACSL异构体和CTE1在心脏中受到不同的调节。利用定量RT-PCR方法，我们报道了五种已知的ACSL亚型(acsl1、acsl3、acsl4、acsl5和acsl6)和cte1在整个大鼠和小鼠心脏以及成年大鼠心肌细胞(Arc)中都有表达。链脲佐菌素诱导的胰岛素依赖型糖尿病(4wk)和空腹(
The molecular mechanism(s) responsible for channeling long-chain fatty acids (LCFAs) into oxidative versus nonoxidative pathways is (are) poorly understood in the heart. Intracellular LCFAs are converted to long-chain fatty acyl-CoAs (LCFA-CoAs) by a family of long-chain acyl-CoA synthetases (ACSLs). Cytosolic thioesterase 1 (CTE1) hydrolyzes cytosolic LCFA-CoAs to LCFAs, generating a potential futile cycle at the expense of ATP utilization. We hypothesized that ACSL isoforms and CTE1 are differentially regulated in the heart during physiological and pathophysiological conditions. Using quantitative RT-PCR, we report that the five known acsl isoforms (acsl1, acsl3, acsl4, acsl5, and acsl6) and cte1 are expressed in whole rat and mouse hearts, as well as adult rat cardiomyocytes (ARCs). Streptozotocin-induced insulin-dependent diabetes (4 wk) and fasting (