Akkaraju G R, Basu A
Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, Texas 76107, USA.
Biochem Biophys Res Commun. 2000 Dec 9;279(1):103-7. doi: 10.1006/bbrc.2000.3903.
The protein kinase C (PKC) signal transduction pathway regulates cell death by tumor necrosis factor-alpha (TNF). We previously showed that the induction of novel PKC eta isozyme by PKC activators correlated with their ability to protect MCF-7 breast cancer cells against TNF cytotoxicity. In the present study, we have transfected PKC eta in MCF-7 cells to directly examine its involvement in cell death by TNF. Overexpression of PKC eta delayed TNF-induced cell death in MCF-7 cells. TNF caused a rapid activation of caspase-8 and -7 in cells transfected with a vector. The activation of these caspases was potentiated by the PKC inhibitor bisindolylmaleimide (BIM) which downregulates PKC eta and sensitizes cells to TNF. Overexpression of PKC eta delayed the activation of caspase-8 and -7 by both TNF and the combination of BIM and TNF. These results suggest that PKC eta protects MCF-7 cells against TNF-induced cell death by preventing the activation of caspases.
蛋白激酶C（PKC）信号转导通路通过肿瘤坏死因子-α（TNF）调节细胞死亡。我们之前发现，PKC激活剂诱导新型PKC η同工酶的产生与其保护MCF-7乳腺癌细胞免受TNF细胞毒性的能力相关。在本研究中，我们将PKC η转染到MCF-7细胞中，以直接检测其在TNF诱导的细胞死亡中的作用。PKC η的过表达延迟了MCF-7细胞中TNF诱导的细胞死亡。TNF在转染载体的细胞中导致caspase-8和-7的快速激活。PKC抑制剂双吲哚马来酰亚胺（BIM）可增强这些半胱天冬酶的激活，BIM可下调PKC η并使细胞对TNF敏感。PKC η的过表达延迟了TNF以及BIM和TNF联合诱导的caspase-8和-7的激活。这些结果表明，PKC η通过阻止半胱天冬酶的激活来保护MCF-7细胞免受TNF诱导的细胞死亡。
