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首页> 外文期刊>Journal of Cellular Physiology >Caspase-3/7 inhibition alters cell morphology in mitomycin-C treated chondrocytes.
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Caspase-3/7 inhibition alters cell morphology in mitomycin-C treated chondrocytes.

机译:Caspase-3/7抑制改变细胞形态mitomycin-C软骨细胞治疗。

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摘要

Apoptosis may play a role in osteoarthritis (OA). Apoptosis can proceed via two different pathways depending on the stimulus. However, both pathways converge upon the effector caspases, caspases-3 and -7. In some systems inhibition of caspases-3 and -7 can prevent apoptosis and may therefore have important therapeutic implications. To confirm this, apoptosis was induced in canine chondrocytes with mitomycin-c (MMC), either in the presence or absence of the general caspase inhibitor, Z-VAD FMK, or a specific caspase-3/7 inhibitor. Z-VAD FMK prevented MMC induced cell death. In contrast, inhibition of caspases-3 and -7 in the presence of MMC induced morphological changes that could be described as necrotic-like or paraptotic-like but did not prevent cell death. The addition of an inhibitor of caspase-8 or caspase-9 along with inhibitor of caspase-3/7 was required to reduce cell death. The morphological changes did not occur in the presence of the caspase-3/7 inhibitor alone and could be prevented by addition of Z-VAD FMK. These data lead to the conclusion that, if the apoptotic program cannot be completed, the cells are pushed into a necrotic or other nonapoptotic mode of death which may involve caspase-8 and/or caspase-9.
机译:细胞凋亡可能发挥作用在骨关节炎(OA)。细胞凋亡可以通过两种不同的途径进行根据不同的刺激。还存在收敛的效应,caspases-3和7。和7可以防止细胞凋亡,因此可能治疗有重要影响。证实了这一点,细胞凋亡诱导犬软骨细胞与mitomycin-c (MMC),要么一般的半胱天冬酶的存在与否抑制剂,Z-VAD FMK或特定caspase-3/7抑制剂。死亡。7在MMC诱发的存在形态可以被描述为necrotic-like变化或paraptotic-like但并没有阻止细胞死亡。或caspase-3/7 caspase-9连同抑制剂被要求减少细胞死亡。形态没有发生变化caspase-3/7抑制剂单独的存在可以通过添加Z-VAD FMK。这些数据导致的结论,如果细胞凋亡程序无法完成,推进坏死或其他nonapoptotic吗模式可能涉及caspase-8和/或死亡caspase-9。

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