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肝脏再生过程中的信号转导:胰岛素和血管加压素的作用

Signal transduction during liver regeneration: role of insulin and vasopressin.

作者信息

Marino M, Mangiantini M T, Spagnuolo S, Luly P, Leoni S

机构信息

Department of Cellular and Developmental Biology, University of Rome La Sapienza, Italy.

出版信息

J Cell Physiol. 1992 Aug;152(2):403-9. doi: 10.1002/jcp.1041520223.

DOI:10.1002/jcp.1041520223
PMID:1639871
Abstract

The relationship between cell proliferation and inositol lipid turnover has been studied by comparing the steady state of inositol derivative metabolism in quiescent and regenerating rat hepatocytes isolated at 4 h (G1 phase of first cell cycle) and 24 h (onset of M phase) after partial hepatectomy. The effect of two hormones able to regulate hepatic regeneration, insulin and vasopressin, has been considered, and the results can be summarized as follows: (i) at 4 h after partial hepatectomy, the precursor incorporation into inositol polyphosphates and the particulate phospholipase C activity increase with respect to quiescent hepatocytes, whereas the content of 11, 4, 5P3 does not change, suggesting an increased turnover of this molecule in this step of cell cycle priming; (ii) 24 h after partial hepatectomy, the radioactivity linked to IP3 and IP4, as well as soluble and particulate phospholipase C activity, and IP3 content increase, suggesting the presence, at the onset of M phase, of second messenger accumulation; (iii) only 24 h after partial hepatectomy, the inositol derivative metabolism is affected by vasopressin; and (iv) insulin exerts a modulatory role on inositol polyphosphate production without involving membrane-bound PLC activity or phosphoinositide hydrolysis. These data suggest that inositol-derived signal molecules are associated with hepatic regeneration; moreover, the metabolic pathway of such compounds seems to be regulated so that only specific inositol phosphates are present in each step of the cell cycle.

摘要

通过比较部分肝切除术后4小时(第一个细胞周期的G1期)和24小时(M期开始)分离的静止和再生大鼠肝细胞中肌醇衍生物代谢的稳态,研究了细胞增殖与肌醇脂质周转之间的关系。研究了两种能够调节肝再生的激素——胰岛素和血管加压素的作用,结果可总结如下:(i)部分肝切除术后4小时,与静止肝细胞相比,前体掺入肌醇多磷酸和微粒体磷脂酶C活性增加,而1,4,5-三磷酸肌醇的含量不变,表明在细胞周期启动的这一步骤中该分子的周转增加;(ii)部分肝切除术后24小时,与肌醇三磷酸和肌醇四磷酸相关的放射性、可溶性和微粒体磷脂酶C活性以及肌醇三磷酸含量增加,表明在M期开始时存在第二信使积累;(iii)仅在部分肝切除术后24小时,肌醇衍生物代谢受血管加压素影响;(iv)胰岛素对肌醇多磷酸的产生发挥调节作用,而不涉及膜结合磷脂酶C活性或磷酸肌醇水解。这些数据表明,肌醇衍生的信号分子与肝再生有关;此外,此类化合物的代谢途径似乎受到调节,以便在细胞周期的每个步骤中仅存在特定的肌醇磷酸。

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