Attenuation of TGF-beta-induced apoptosis in primary cultures of hepatocytes by calpain inhibitors
Attenuation of TGF-beta-induced apoptosis in primary cultures of hepatocytes by calpain inhibitors
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DOI：
10.1006/bbrc.1996.5777
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发表时间：
1997-02-13
影响因子：
3.1
通讯作者：
Roth, S
中科院分区：
文献类型：
--
作者：
Gressner, AM;Lahme, B;Roth, S
在大鼠肝细胞原代培养物中通过转化生长因子β(1) (TGF-β(1))诱导的细胞凋亡分别被钙蛋白酶I和钙蛋白酶II的抑制剂(5μM)大大减弱。两种抑制剂均可阻止 TGF-β 引起的核小体 DNA 片段的增加以及 TUNEL 反应中 DNA 断裂的发生。通过 WST-1 测试测得的 TGF-β 对细胞活力的有害影响被钙蛋白酶抑制剂大大降低。 Calpain II > I 抑制剂可抑制培养过程中肝细胞中的自发 DNA 裂解，并阻止免疫细胞化学上可见的 TGF-β（APAAP 染色）的出现，这种现象发生在未经处理的实质细胞培养物中。数据表明，钙蛋白酶失活可减弱 TGF-β 诱导的培养肝细胞的自发凋亡；后一种作用可能是由于内源性 TGF-β 激活的抑制。建议钙蛋白酶参与这些过程。 (C) 1997 年学术出版社。
Apoptosis induced in primary cultures of rat hepatocytes by transforming growth factor beta(1) (TGF-beta(1)) was greatly attenuated by inhibitors (5 mu M) of calpain I and calpain II, respectively. Both inhibitors prevented the TGF-beta-elicited increase of nucleosomal DNA fragments and the occurrence of DNA-breaks in the TUNEL reaction. The detrimental effect of TGF-beta on cell viability measured by the WST-1 test was strongly reduced by calpain inhibitors. Calpain II > I inhibitors suppressed spontaneous DNA cleavage in hepatocytes during culture and prevented the appearance of immunocytochemically visible TGF-beta (APAAP staining), which occurs in untreated parenchymal cell cultures. The data show that inactivation of calpains attenuates both the TGF-beta-elicited and the spontaneous apoptosis of cultured hepatocytes; the latter effect is likely due to the suppression of endogenous TGF-beta activation. It is suggested that calpains participate in these processes. (C) 1997 Academic Press.