Cell cycle delay and apoptosis in response to osmotic stress
Cell cycle delay and apoptosis in response to osmotic stress
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DOI：
10.1016/s1095-6433(01)00439-1
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发表时间：
2001-10-01
影响因子：
2.3
通讯作者：
Burg, MB
中科院分区：
文献类型：
--
作者：
Dmitrieva, NI;Michea, LF;Burg, MB
作为尿浓缩机制的一部分，肾内髓质细胞可能暴露于极端可变的NaCl和尿素浓度，其可达到非常高的水平。本文综述了一些研究，旨在了解这种渗透胁迫如何影响细胞以及可能存在的保护机制。这些研究中的大多数是在组织培养中连续生长的内髓上皮细胞（mIMCD 3）上进行的。在300 mosmol/kg下生长的细胞存活通过添加NaCl或尿素增加至500 mosmol/ka，但仅在生长停滞类似于24 h之后。在较高的渗透压（650-700 mosmol/kg）下，大多数细胞在数小时内通过凋亡而死亡。细胞在体内外通过多种机制适应高渗透压，包括多种有机渗透压物质的积累和热休克蛋白的诱导。细胞周期延迟是由于G1和G2/M检查点的阻滞和S期的减慢所致。加入NaCl而不是尿素后，p53（肿瘤抑制蛋白）的量和转录活性增加。p53在ser-15上磷酸化，并且在500 mosmol/kg（与细胞存活相关）下具有转录活性，但在700 mosmol/ka（与凋亡相关）下不具有转录活性。p53反义寡核苷酸降低p53表达增加培养肾细胞对NaCl引起的高渗应激的敏感性。并对p53抗高渗应激保护作用的可能机制进行了讨论。(C)2001年由Elsevier Science Inc.出版
As part of the urinary concentrating mechanism, renal inner medulla cells may be exposed to extremely variable NaCl and urea concentrations that can reach very high levels. A number of studies, reviewed herein, aim to understand how such osmotic stress affects the cells and what protective mechanisms might exist. The majority of these studies are done on inner medullary epithelial cells that grow continuously in tissue culture (mIMCD3). Cells grown at 300 mosmol/kg survive increase to 500 mosmol/ka by adding NaCl or urea, but only after a growth arrest of similar to 24 h. At a higher osmolality (650-700 mosmol/kg) most cells die within hours by apoptosis. The cells both in vitro and in vivo adapt to high osmolality by a number of mechanisms, including accumulation of variety of organic osmolytes and induction of heat shock proteins. The cell cycle delay results from blocks at the G1 and G2/M checkpoints and slowing during S. After adding NaCl, but not urea, the amount and transcriptional activity of p53 (the tumor suppressor protein) increases. The p53 is phosphorylated on ser-15 and is transcriptionally active at 500 mosmol/kg (associated with cell survival), but not at 700 mosmol/ka (associated with apoptosis). Reduction of p53 expression by p53 antisense oligonucleotide increases sensitivity of renal cells in culture to hyperosmotic stress caused by NaCl. The possible mechanisms of the protection action of p53 against hypertonic stress are discussed. (C) 2001 Published by Elsevier Science Inc.