Osmotic stress induces both secretion and apoptosis in rat alveolar type II cells

被引:35
作者
Edwards, YS
Sutherland, LM
Power, JHT
Nicholas, TE
Murray, AW
机构
[1] Flinders Univ S Australia, Fac Sci & Engn, Sch Biol Sci, Adelaide, SA 5001, Australia
[2] Flinders Univ S Australia, Sch Med, Dept Human Physiol, Adelaide, SA 5001, Australia
关键词
sorbitol; 12-O-tetradecanoylphorbol; 13-acetate; adenosine 5 '-triphosphate; mitogen-activated protein kinase; stress-activated signaling;
D O I
10.1152/ajplung.1998.275.4.L670
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
The aim of this study was to analyze the effects of osmotic shock and secretagogues such as ATP and 12-O-tetradecanoylphorbol 13-acetate (TPA) on various intracellular signaling pathways in primary cultures of alveolar type II cells and examine their potential role in regulating events such as secretion and apoptosis in these cells. Sorbitol-induced osmotic stress caused the sustained release of [H-3]phosphatidylcholine ([H-3]PC)from primary cultures of rat alveolar type II cells prelabeled with [H-3]choline chloride. This release was not dependent on protein kinase C because downregulation of the major protein kinase C isoforms (alpha, beta(II), delta, and eta) expressed in alveolar type II cells had no effect on [H-3]PC secretion. Sorbitol, as well as the known secretagogues TPA and ATP, activated extracellular signal-regulated kinase. Although an inhibitor of the extracellular signal-regulated kinase cascade, PD-98059, blocked this activation, it had no effect on the release of [H-3]PC. Sorbitol and ultraviolet C radiation, but not TPA or ATP, were also found to activate both p38 and stress-activated protein kinase/c-Jun NH2-terminal kinase. Furthermore, both sorbitol and ultraviolet C radiation induced apoptosis in alveolar type II cells as demonstrated by Hoechst 33258 staining of the condensed nuclei, the generation of DNA ladders, and the activation of caspases. The data indicate that multiple signaling pathways are activated by traditional secretagogues such as TPA and ATP and by cellular stresses such as osmotic shock and that these may be involved in regulating secretory and apoptotic events in alveolar type II cells.
引用
收藏
页码:L670 / L678
页数:9
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