• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Mouse Cardiac Acyl Coenzyme A Synthetase 1 Deficiency Impairs Fatty Acid Oxidation and Induces Cardiac Hypertrophy
【24h】

Mouse Cardiac Acyl Coenzyme A Synthetase 1 Deficiency Impairs Fatty Acid Oxidation and Induces Cardiac Hypertrophy

机译：小鼠心脏酰基辅酶A合成酶1缺乏症损害脂肪酸氧化并诱导心肌肥大。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Long-chain acyl coenzyme A (acyl-CoA) synthetase isoform 1 (ACSL1) catalyzes the synthesis of acyl-CoA from long-chain fatty acids and contributes the majority of cardiac long-chain acyl-CoA synthetase activity. To understand its functional role in the heart, we studied mice lacking ACSL1 globally (Acsl1T?/?) and mice lacking ACSL1 in heart ventricles (Acsl1H?/?) at different times. Compared to littermate controls, heart ventricular ACSL activity in Acsl1T?/? mice was reduced more than 90%, acyl-CoA content was 65% lower, and long-chain acyl-carnitine content was 80 to 90% lower. The rate of [14C]palmitate oxidation in both heart homogenate and mitochondria was 90% lower than in the controls, and the maximal rates of [14C]pyruvate and [14C]glucose oxidation were each 20% higher. The mitochondrial area was 54% greater than in the controls with twice as much mitochondrial DNA, and the mRNA abundance of Pgc1α and Errα increased by 100% and 41%, respectively. Compared to the controls, Acsl1T?/? and Acsl1H?/? hearts were hypertrophied, and the phosphorylation of S6 kinase, a target of mammalian target of rapamycin (mTOR) kinase, increased 5-fold. Our data suggest that ACSL1 is required to synthesize the acyl-CoAs that are oxidized by the heart, and that without ACSL1, diminished fatty acid (FA) oxidation and compensatory catabolism of glucose and amino acids lead to mTOR activation and cardiac hypertrophy without lipid accumulation or immediate cardiac dysfunction.
机译：长链酰基辅酶A（酰基辅酶A）合成酶同工型1（ACSL1）催化长链脂肪酸合成酰基辅酶A并贡献了大部分心脏长链酰基辅酶A合成酶的活性。为了了解其在心脏中的功能，我们研究了整体缺乏ACSL1的小鼠（ Acsl1 T ？/？）和缺乏心室的ACSL1的小鼠（ Acsl1 H ？/？）在不同的时间。与同窝对照相比， Acsl1 T ？/？小鼠的心室ACSL活性降低了90％以上，酰基辅酶A含量为65 ％降低，长链酰基肉碱含量降低80％至90％。心脏匀浆和线粒体中[ 14 C]棕榈酸的氧化率均比对照组低90％，[ 14 C]丙酮酸盐和[[ 14 C]葡萄糖氧化分别增加20％。线粒体面积比线粒体DNA两倍的对照大54％， Pgc1 α和 Err α的mRNA丰度分别增加了100％和41％，分别。与对照相比， Acsl1 T ？/？和 Acsl1 H ？/？心脏肥大，哺乳动物雷帕霉素（mTOR）激酶靶标S6激酶的磷酸化增加了5倍。我们的数据表明需要ACSL1来合成被心脏氧化的酰基辅酶A，而没有ACSL1的话，脂肪酸（FA）的氧化作用减弱以及葡萄糖和氨基酸的代偿分解代谢会导致mTOR活化和心肌肥大，而没有脂质蓄积或立即出现心脏功能障碍。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号