Das S, Bhattacharyya S, Ghosh S, Majumdar S
Department of Microbiology, Bose Institute, Calcutta, India.
Mol Cell Biochem. 1999 Jul;197(1-2):97-108. doi: 10.1023/a:1006935114624.
In the present study we investigated the TNF-alpha induced signal transduction mechanism in human neutrophil. Exogenously added TNF-alpha affects both PKC activity and its translocation from cytosol to the membrane. Endogenous protein phosphorylation pattern is inhibited in TNF-alpha induced neutrophil in Ca-dependent and Ca-independent manner, including a major 47 and 66 kDa cytosolic proteins, which may be implicated in superoxide anion generation. However TNF-alpha dose dependently enhances the expression of zeta-PKC isotype but not the beta-PKC. Morphology and cell cytotoxicity are studied in TNF-alpha treated neutrophil to understand the TNF-alpha induced cell death or apoptosis and these experiment is further confirmed by DNA fragmentation analysis. These results clearly demonstrate that TNF-alpha induces cellular death of human neutrophil at least in part by enhanced expression of Ca-independent zeta-PKC. These observations provide an insight towards understanding the function of zeta-PKC in apoptotic pathway.
在本研究中，我们调查了肿瘤坏死因子-α（TNF-α）在人中性粒细胞中诱导的信号转导机制。外源性添加的TNF-α影响蛋白激酶C（PKC）的活性及其从胞质溶胶向细胞膜的转位。内源性蛋白质磷酸化模式在TNF-α诱导的中性粒细胞中以钙依赖性和非钙依赖性方式受到抑制，包括主要的47 kDa和66 kDa胞质蛋白，这可能与超氧阴离子的产生有关。然而，TNF-α剂量依赖性地增强了ζ-PKC同工型的表达，但不增强β-PKC的表达。在TNF-α处理的中性粒细胞中研究形态学和细胞毒性，以了解TNF-α诱导的细胞死亡或凋亡，并且这些实验通过DNA片段化分析得到进一步证实。这些结果清楚地表明，TNF-α至少部分地通过增强非钙依赖性ζ-PKC的表达来诱导人中性粒细胞的细胞死亡。这些观察结果为理解ζ-PKC在凋亡途径中的功能提供了见解。
