为探究绵羊长链脂酰辅酶A合成酶1基因(ACSL1)编码蛋白的结构与功能,通过生物信息学分析对绵羊ACSL1蛋白的二、三级结构预测,分析其信号肽剪切位点、理化性质、亲/疏水性、亚细胞定位和蛋白互作网络通路。结果表明,ACSL1基因共编码699个...为探究绵羊长链脂酰辅酶A合成酶1基因(ACSL1)编码蛋白的结构与功能,通过生物信息学分析对绵羊ACSL1蛋白的二、三级结构预测,分析其信号肽剪切位点、理化性质、亲/疏水性、亚细胞定位和蛋白互作网络通路。结果表明,ACSL1基因共编码699个氨基酸,理论分子量78.21 k D,理论等电点8.0,具有1个跨膜结构域,编码蛋白的不稳定系数33.23,主要分布在细胞质(26.1%)、线粒体(13%)和内质网(13%),无信号肽,是一种疏水性稳定蛋白。其蛋白结构主要以α螺旋和无规则卷曲为主,其中共有276个α螺旋(39.48%),148个β折叠(21.17%),217个无规则卷曲(31.04%),折叠缠绕后形成三级结构。绵羊ACSL1蛋白主要与FADS1、FADS2、ACOX1、ACOX2、LPL、MGLL、ELOVL6、ACADL等9个蛋白相关,可能处在同一信号通路,通过与疏水性蛋白结合后,在机体内调节其生物学功能。展开更多
长链脂酰辅酶A合成酶(acyl-CoA synthetase long-chain,ACSL)属于多基因家族编码的酶,位于内质网和线粒体外膜上的ACSL主要催化脂肪酸形成脂酰辅酶A(acyl-CoA),参与脂肪酸代谢、膜修饰等多种生理过程。ACSL家族在不同细胞的脂肪酸代谢...长链脂酰辅酶A合成酶(acyl-CoA synthetase long-chain,ACSL)属于多基因家族编码的酶,位于内质网和线粒体外膜上的ACSL主要催化脂肪酸形成脂酰辅酶A(acyl-CoA),参与脂肪酸代谢、膜修饰等多种生理过程。ACSL家族在不同细胞的脂肪酸代谢中发挥不同作用,其功能异常可导致如脂肪肝、动脉粥样硬化和糖尿病的发生。ACSL家族成员1(ACSL family member 1,ACSL1)作为ACSL家族在肝脏中的主要亚型,主要参与维持胆固醇稳定、脂肪酸活化以及胆汁酸代谢,同时与某些肝脏疾病如肝细胞癌、非酒精性脂肪肝的发生发展密切相关。本文综述了ACSL家族各成员的生理功能、作用特点,并阐释了ACSL1对脂质代谢、调节细胞铁死亡的影响以及在相关疾病如肝纤维化、肝细胞癌、恶病质、非酒精性脂肪肝、甲状腺癌以及乳腺癌发展中的作用机制的研究进展。展开更多
Atherosclerosis is characterized by inflammation in the arterial wall,which is known to be exacerbated by diabetes.Therapeutic repression of inflammation is a promising strategy for treating atherosclerosis.In this st...Atherosclerosis is characterized by inflammation in the arterial wall,which is known to be exacerbated by diabetes.Therapeutic repression of inflammation is a promising strategy for treating atherosclerosis.In this study,we showed that diabetes aggravated atherosclerosis in apolipoproteinE knockout(ApoE^(-/-))mice,in which increased expression of long-chain acyl-CoA synthetase 1(Acsl1)in macrophages played an important role.Knockdown of Acsl1 in macrophages(Mφ^(shAcsl1))reprogrammed macrophages to an anti-inflammatory phenotype,especially under hyperglycemic conditions.Injection of Mφ^(shAcsl1) reprogrammed macrophages into streptozotocin(STZ)-induced diabetic ApoE^(-/-) mice(ApoE^(-/-)+STZ)alleviated inflammation locally in the plaque,liver and spleen.Consistent with the reduction in inflammation,plaques became smaller and more stable after the adoptive transfer of reprogrammed macrophages.Taken together,our findings indicate that increased Acsl1 expression in macrophages play a key role in aggravated atherosclerosis of diabetic mice,possibly by promoting inflammation.Adoptive transfer of Acsl1 silenced macrophages may serve as a potential therapeutic strategy for atherosclerosis.展开更多
文摘为探究绵羊长链脂酰辅酶A合成酶1基因(ACSL1)编码蛋白的结构与功能,通过生物信息学分析对绵羊ACSL1蛋白的二、三级结构预测,分析其信号肽剪切位点、理化性质、亲/疏水性、亚细胞定位和蛋白互作网络通路。结果表明,ACSL1基因共编码699个氨基酸,理论分子量78.21 k D,理论等电点8.0,具有1个跨膜结构域,编码蛋白的不稳定系数33.23,主要分布在细胞质(26.1%)、线粒体(13%)和内质网(13%),无信号肽,是一种疏水性稳定蛋白。其蛋白结构主要以α螺旋和无规则卷曲为主,其中共有276个α螺旋(39.48%),148个β折叠(21.17%),217个无规则卷曲(31.04%),折叠缠绕后形成三级结构。绵羊ACSL1蛋白主要与FADS1、FADS2、ACOX1、ACOX2、LPL、MGLL、ELOVL6、ACADL等9个蛋白相关,可能处在同一信号通路,通过与疏水性蛋白结合后,在机体内调节其生物学功能。
文摘长链脂酰辅酶A合成酶(acyl-CoA synthetase long-chain,ACSL)属于多基因家族编码的酶,位于内质网和线粒体外膜上的ACSL主要催化脂肪酸形成脂酰辅酶A(acyl-CoA),参与脂肪酸代谢、膜修饰等多种生理过程。ACSL家族在不同细胞的脂肪酸代谢中发挥不同作用,其功能异常可导致如脂肪肝、动脉粥样硬化和糖尿病的发生。ACSL家族成员1(ACSL family member 1,ACSL1)作为ACSL家族在肝脏中的主要亚型,主要参与维持胆固醇稳定、脂肪酸活化以及胆汁酸代谢,同时与某些肝脏疾病如肝细胞癌、非酒精性脂肪肝的发生发展密切相关。本文综述了ACSL家族各成员的生理功能、作用特点,并阐释了ACSL1对脂质代谢、调节细胞铁死亡的影响以及在相关疾病如肝纤维化、肝细胞癌、恶病质、非酒精性脂肪肝、甲状腺癌以及乳腺癌发展中的作用机制的研究进展。
基金funded by the National Natural Science Foundation of China(No,81671910 to X Yang)Shanxi Province Foundation of China(No.2021SF-341 to X Yang).
文摘Atherosclerosis is characterized by inflammation in the arterial wall,which is known to be exacerbated by diabetes.Therapeutic repression of inflammation is a promising strategy for treating atherosclerosis.In this study,we showed that diabetes aggravated atherosclerosis in apolipoproteinE knockout(ApoE^(-/-))mice,in which increased expression of long-chain acyl-CoA synthetase 1(Acsl1)in macrophages played an important role.Knockdown of Acsl1 in macrophages(Mφ^(shAcsl1))reprogrammed macrophages to an anti-inflammatory phenotype,especially under hyperglycemic conditions.Injection of Mφ^(shAcsl1) reprogrammed macrophages into streptozotocin(STZ)-induced diabetic ApoE^(-/-) mice(ApoE^(-/-)+STZ)alleviated inflammation locally in the plaque,liver and spleen.Consistent with the reduction in inflammation,plaques became smaller and more stable after the adoptive transfer of reprogrammed macrophages.Taken together,our findings indicate that increased Acsl1 expression in macrophages play a key role in aggravated atherosclerosis of diabetic mice,possibly by promoting inflammation.Adoptive transfer of Acsl1 silenced macrophages may serve as a potential therapeutic strategy for atherosclerosis.
