Succinate is a paracrine signal for liver damage
Succinate is a paracrine signal for liver damage
复制标题
DOI：
10.1016/j.jhep.2007.03.016
复制
发表时间：
2007-08-01
影响因子：
25.7
通讯作者：
Nathanson, Michael H.
中科院分区：
文献类型：
--
作者：
Correa, Paulo Renato A. V.;Kruglov, Emma A.;Nathanson, Michael H.
背景/目的：最近在包括肝脏在内的几个组织中发现了一种G蛋白偶联的琥珀酸受体。本工作的目的是确定表达该受体的肝细胞类型，并确定其生理作用。方法：采用RT-PCR和共聚焦免疫荧光法检测琥珀酸受体的表达和分布。采用生化方法测定琥珀酸和环磷酸腺苷。用时移成像技术监测单细胞内钙离子浓度。结果：在静止的肝星状细胞中有琥珀酸受体的表达，且随着活化程度的增加，琥珀酸受体的表达减少。缺血诱导离体灌流肝脏中琥珀酸释放。与在细胞表达系统中观察到的相反，琥珀酸不抑制原代肝星状细胞cAMP的产生或增加胞内钙离子。结论：肝星状细胞表达琥珀酸受体。琥珀酸可能作为旁分泌信号，通过缺血肝细胞触发星状细胞激活。(C)2007年欧洲肝脏研究协会。爱思唯尔出版，版权所有。
Background/Aims: A G-protein-coupled succinate receptor has recently been identified in several tissues, including the liver. The objectives of this work were to determine the hepatic cell types that express this receptor and to determine its physiological role.Methods: Expression and distribution of the succinate receptor was determined by RT-PCR and confocal immunofluorescence. Biochemical assays were used to measure succinate and cAMP. Cytosolic Ca2+ was monitored in single cells by time-lapse imaging. Western blot was used to study the effect of succinate on activation of hepatic stellate cells.Results: The succinate receptor was expressed in quiescent hepatic stellate cells, and -expression decreased with activation. Ischemia induced release of succinate in isolated perfused livers. In contrast to what is observed in cell expression systems, succinate did not inhibit cAMP production or increase cytosolic Ca (2+) in primary hepatic stellate cells. However, succinate accelerated stellate cell activation.Conclusions: Hepatic stellate cells express the succinate receptor. Succinate may behave as a paracrine signal by which ischemic hepatocytes trigger stellate cell activation. (C) 2007 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.