Caspase-mediated protein kinase C-δ cleavage is necessary for apoptosis of vascular smooth muscle cells
Caspase-mediated protein kinase C-δ cleavage is necessary for apoptosis of vascular smooth muscle cells
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DOI：
10.1152/ajpheart.00274.2009
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发表时间：
2009-12-01
影响因子：
4.8
通讯作者：
Liu, Bo
中科院分区：
文献类型：
--
作者：
Kato, Kaori;Yamanouchi, Dai;Liu, Bo
Kato K, Yamanouchi D, Esbona K, Kamiya K，张峰，Kent KC, Liu B. caspase介导的蛋白激酶c - δ切割在血管平滑肌细胞凋亡中的作用。[J] .中华心脏杂志，2009,31(4):559 - 561。首次发表于2009年10月16日；doi: 10.1152 / ajpheart.00274.2009。血管平滑肌细胞（SMCs）的凋亡是血管重构和各种血管疾病的显著特征。我们之前已经证明蛋白激酶c - δ (pkc - δ)在SMC凋亡中起关键作用。在这项研究中，我们测试了pkc - δ蛋白水解裂解和酪氨酸磷酸化在细胞凋亡途径中的重要性。使用过氧化氢作为氧化应激的范例，我们发现PKC-delta的蛋白水解裂解发生在凋亡的SMCs中，而酪氨酸磷酸化仅在坏死细胞中检测到。此外，利用一种模拟PKC-delta连接区域内caspase-3结合基序的肽（z-DIPD-fmk），我们能够阻止PKC-delta的切割和细胞凋亡。用rotlerin或小干扰RNA抑制PKC-delta可减少caspase-3的切割、caspase-3的活性、聚腺苷（ADPribose）聚合酶的切割、PKC-delta的切割和DNA的断裂，证实了先前报道的PKC-delta在细胞凋亡起始中的作用。相比之下，z-DIPD-fmk显著降低了caspase-3活性、PKC-delta的切割和DNA断裂，但不影响caspase-3和聚adp核糖聚合酶的切割。综上所述，我们的数据表明，caspase-3介导的PKC-delta切割是氧化应激诱导SMC凋亡的基础，PKC-delta在caspase-3的上游和下游都起作用。
Kato K, Yamanouchi D, Esbona K, Kamiya K, Zhang F, Kent KC, Liu B. Caspase-mediated protein kinase C-delta cleavage is necessary for apoptosis of vascular smooth muscle cells. Am J Physiol Heart Circ Physiol 297: H2253-H2261, 2009. First published October 16, 2009; doi:10.1152/ajpheart.00274.2009.-Apoptotic death of vascular smooth muscle cells (SMCs) is a prominent feature of blood vessel remodeling and various vascular diseases. We have previously shown that protein kinase C-delta(PKC-delta) plays a critical role in SMC apoptosis. In this study, we tested the importance of PKC-delta proteolytic cleavage and tyrosine phosphorylation within the apoptosis pathway. Using hydrogen peroxide as a paradigm for oxidative stress, we showed that proteolytic cleavage of PKC-delta occurred in SMCs that underwent apoptosis, while tyrosine phosphorylation was detected only in necrotic cells. Furthermore, using a peptide (z-DIPD-fmk) that mimics the caspase-3 binding motif within the linker region of PKC-delta, we were able to prevent the cleavage of PKC-delta, as well as apoptosis. Inhibition of PKC-delta with rottlerin or small-interfering RNA diminished caspase-3 cleavage, caspase-3 activity, cleavage of poly (ADPribose) polymerase, cleavage of PKC-delta, and DNA fragmentation, confirming the previously reported role of PKC-delta in initiation of apoptosis. In contrast, z-DIPD-fmk markedly diminished caspase-3 activity, cleavage of PKC-delta, and DNA fragmentation without affecting cleavage of caspase-3 and poly (ADP-ribose) polymerase. Taken together, our data suggest that caspase-3-mediated PKC-delta cleavage underlies SMC apoptosis induced by oxidative stress, and that PKC-delta acts both upstream and downstream of caspase-3.