Differential Effects of Sphingomyelin Hydrolysis and Cholesterol Transport on Oxysterol-binding Protein Phosphorylation and Golgi Localization*
Differential Effects of Sphingomyelin Hydrolysis and Cholesterol Transport on Oxysterol-binding Protein Phosphorylation and Golgi Localization*
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鞘磷脂水解和胆固醇转运对氧固醇结合蛋白磷酸化和高尔基体定位的不同影响*
DOI：
--
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发表时间：
1998
影响因子：
4.8
通讯作者：
D. Byers
中科院分区：
文献类型：
--
作者：
N. Ridgway;Thomas A. Lagace;H. W. Cook;D. Byers
新生合成胆固醇和脂蛋白衍生胆固醇在质膜上的沉积和向内质网的转运依赖于鞘磷脂（SM）的含量。本研究表明，外源性细菌鞘磷脂酶水解中国仓鼠卵巢细胞质膜SM，导致内质网胆固醇酯化反应增强，并导致氧甾醇结合蛋白（OSBP）快速去磷酸化，OSBP是一种胞质/高尔基受体，可接受25-羟基胆固醇等氧甾醇。鞘磷脂酶处理后，OSBP磷酸化的恢复与SM的再合成和胆固醇酯合成的下调密切相关。SM水解激活了短链神经酰胺在中国仓鼠卵巢细胞中未激活的冈田酸敏感磷酸酶。特异性阻断鞘磷脂酶介导的胆固醇向酰基辅酶a的传递：胆固醇酰基转移酶（U18666A）或促进胆固醇向介质的外排（环糊精）的药物不抑制OSBP的去磷酸化。SM水解也促进OSBP从囊室向高尔基体转运。环糊精和U18666A也引起OSBP向高尔基体的移位，提示OSBP的移动与质膜或高尔基体胆固醇含量的变化有关。这些结果表明OSBP是SM转化和胆固醇在质膜和/或高尔基体动员的潜在靶点。
The deposition of de novo synthesized and lipoprotein-derived cholesterol at the plasma membrane and transport to the endoplasmic reticulum is dependent on sphingomyelin (SM) content. Here we show that hydrolysis of plasma membrane SM in Chinese hamster ovary cells by exogenous bacterial sphingomyelinase resulted in enhanced cholesterol esterification at the endoplasmic reticulum and rapid dephosphorylation of the oxysterol-binding protein (OSBP), a cytosolic/Golgi receptor for oxysterols such as 25-hydroxycholesterol. After sphingomyelinase treatment, restoration of OSBP phosphorylation closely paralleled resynthesis of SM and down-regulation of cholesterol ester synthesis. SM hydrolysis activated an okadaic acid-sensitive phosphatase that was not stimulated in Chinese hamster ovary cells by short chain ceramides. Agents that specifically blocked sphingomyelinase-mediated delivery of cholesterol to acyl-CoA:cholesterol acyltransferase (U18666A) or promoted cholesterol efflux to the medium (cyclodextrin) did not inhibit OSBP dephosphorylation. SM hydrolysis also promoted OSBP translocation from a vesicular compartment to the Golgi apparatus. Cyclodextrin and U18666A also caused OSBP translocation to the Golgi apparatus, suggesting that OSBP movement is coupled to changes in the cholesterol content of the plasma membrane or Golgi apparatus. These results identify OSBP as a potential target of SM turnover and cholesterol mobilization at the plasma membrane and/or Golgi apparatus.
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DOI：
10.1016/s0021-9258(18)42727-5
发表时间：
1992-03
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
R. Dobrowsky;Yueuf A. Hannung
通讯作者：
R. Dobrowsky;Yueuf A. Hannung
影响因子：
--
作者：
J. Goldstein;S. Basu;Michael S. Brown
通讯作者：
J. Goldstein;S. Basu;Michael S. Brown
DOI：
--
发表时间：
1989-03
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Y. Lange;M. Swaisgood;B. Ramos;T. Steck
通讯作者：
Y. Lange;M. Swaisgood;B. Ramos;T. Steck
影响因子：
6.5
作者：
K. Underwood;B. Andemariam;G. L. McWilliams;L. Liscum
通讯作者：
K. Underwood;B. Andemariam;G. L. McWilliams;L. Liscum
DOI：
10.1016/s0021-9258(18)82288-8
发表时间：
1993-07
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Rick T. DobrowskySS;Craig Kamibayashili;Marc C. Mumbyli;Yusuf A. HannunSIJ
通讯作者：
Rick T. DobrowskySS;Craig Kamibayashili;Marc C. Mumbyli;Yusuf A. HannunSIJ