由鞘磷脂水解和补救途径产生的神经酰胺参与缺氧/复氧诱导的NT-2细胞中Bax向线粒体的重新分布。
Ceramide generated by sphingomyelin hydrolysis and the salvage pathway is involved in hypoxia/reoxygenation-induced Bax redistribution to mitochondria in NT-2 cells.
作者信息
Jin Junfei, Hou Qi, Mullen Thomas D, Zeidan Youssef H, Bielawski Jacek, Kraveka Jacqueline M, Bielawska Alicja, Obeid Lina M, Hannun Yusuf A, Hsu Yi-Te
机构信息
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
出版信息
J Biol Chem. 2008 Sep 26;283(39):26509-17. doi: 10.1074/jbc.M801597200. Epub 2008 Aug 1.
Abstract
Ceramide functions as an important second messenger in apoptosis signaling pathways. In this report, we show that treatment of NT-2 neuronal precursor cells with hypoxia/reoxygenation (H/R) resulted in ceramide up-regulation. This elevation in ceramide was primarily due to the actions of acid sphingomyelinase and ceramide synthase LASS 5, demonstrating the action of the salvage pathway. Hypoxia/reoxygenation treatment led to Bax translocation from the cytoplasm to mitochondria and cytochrome c release from mitochondria. Down-regulation of either acid sphingomyelinase or LASS 5-attenuated ceramide accumulation and H/R-induced Bax translocation to mitochondria. Overall, we have demonstrated that ceramide up-regulation following H/R is pertinent to Bax activation to promote cell death.
摘要
神经酰胺在细胞凋亡信号通路中作为重要的第二信使发挥作用。在本报告中，我们表明用缺氧/复氧（H/R）处理NT-2神经前体细胞会导致神经酰胺上调。神经酰胺的这种升高主要归因于酸性鞘磷脂酶和神经酰胺合酶LASS 5的作用，这证明了补救途径的作用。缺氧/复氧处理导致Bax从细胞质转移到线粒体以及细胞色素c从线粒体释放。酸性鞘磷脂酶或LASS 5的下调会减弱神经酰胺积累以及H/R诱导的Bax向线粒体的转移。总体而言，我们已经证明H/R后神经酰胺上调与Bax激活以促进细胞死亡相关。
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