The η isoform of protein kinase C inhibits UV-induced activation of caspase-3 in normal human keratinocytes
The η isoform of protein kinase C inhibits UV-induced activation of caspase-3 in normal human keratinocytes
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DOI：
10.1016/s0006-291x(03)00345-0
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发表时间：
2003-03-28
影响因子：
3.1
通讯作者：
Ohba, M
中科院分区：
文献类型：
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作者：
Matsumura, M;Tanaka, N;Ohba, M
蛋白激酶C（PKC）在决定角质形成细胞的细胞命运中发挥着核心作用。PKC δ和PKCeta均诱导正常人角质形成细胞（NHK）的生长抑制和分化。在这里，我们表明，PKC δ和PKCeta在UVB诱导的NHK细胞凋亡中发挥相反的作用。PKC δ增强UVB诱导的caspase-3活性，而过度表达PKCeta则降低caspase-3活性。与这些观察结果一致，PKC δ的显性负突变体显著抑制caspase-3的活化，而显性负突变体PKCeta以剂量（MOI）依赖的方式增加caspase-3的活化。与PKC δ不同，未观察到PKC δ的裂解和易位至线粒体，导致未检测到细胞色素c释放。此外，紫外线诱导的p38 MAP激酶的激活，抑制caspase-3的活性在NHK，被阻断显性负PKCeta。这些研究结果表明，PKCeta负调控紫外线诱导的细胞凋亡，通过其本地化，抗裂解，和p38 MAPK途径。(C)2003 Elsevier Science（美国）。All rights reserved.
Protein kinase C (PKC) fulfills a central role in the decision of cell fate in keratinocytes. Both PKCdelta and PKCeta induce growth inhibition and differentiation of normal human keratinocytes (NHK). Here we show that PKCdelta and PKCeta play opposite roles in UVB-induced apoptosis in NHK. PKCdelta enhanced UVB-induced caspase-3 activity, while overexpression of PKCeta reduced it. In keeping with these observations, the dominant negative mutant of PKCdelta significantly inhibited the activation of caspase-3, whereas dominant negative PKCeta increased it in a dose (MOI)-dependent manner. Unlike PKCdelta, cleavage and translocation to mitochondria of PKCeta were not observed, resulting in no detection of cytochorome c release. Furthermore, UV-induced activation of p38 MAP kinase, which suppressed the caspase-3 activity in NHK, was blocked by dominant negative PKCeta. These findings suggest that PKCeta negatively regulates UV-induced apoptosis through its localization, resistance to cleavage, and the p38 MAPK pathway. (C) 2003 Elsevier Science (USA). All rights reserved.