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首页> 外文期刊>Journal of Cellular Physiology >Parathyroid hormone related protein (PTHrP) inhibits TNFalpha-induced apoptosis by blocking the extrinsic and intrinsic pathways.
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Parathyroid hormone related protein (PTHrP) inhibits TNFalpha-induced apoptosis by blocking the extrinsic and intrinsic pathways.

机译：甲状旁腺激素相关蛋白(PTHrP)抑制TNFalpha-induced通过阻断细胞凋亡外在和内在的途径。

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摘要

Parathyroid hormone related protein (PTHrP) is expressed at low levels in many fetal and adult tissues where it plays a central role in regulating cell proliferation, cell death, and tissue homeostasis. In vivo and in vitro, PTHrP has been shown to promote the survival of a variety of cells by regulating expression of the anti-apoptotic protein Bcl2. Additional work has shown that intra-nuclear accumulation of PTHrP in CFK2 (PTH1R positive) and 27m21 (PTH1R negative) condrogenic cells promotes their survival by closing down ribosome biogenesis and promoting quiescence. The current studies were undertaken to examine the role of wild-type PTHrP and a mutant form that cannot translocate to the nucleus in protecting cells from TNFalpha-induced apoptosis. Both forms of the protein were equally effective in blocking the extrinsic pathway by inhibiting expression of the TNF receptor death domain, activating Bid, and promoting cleavage of caspase 8. These observations suggest a direct mechanism of PTHrP actionon components of the extrinsic pathway, involving a region of the protein outside of the NTS. PTHrP and M1PTHrP also inhibited the intrinsic pathway by preventing the exchange of anti-apoptotic for pro-apoptotic proteins at the mitochondrial membrane, thus maintaining its integrity and preventing the release of caspase-activating factors into the cytosol. In general, this mitochondrial-related activity was somewhat delayed and was mediated more effectively by PTHrP than by M1PTHrP, suggesting an indirect mechanism of action that might require the presence of an intact NTS.
机译：甲状旁腺激素相关蛋白(PTHrP)在许多胎儿和成人在低水平表达组织中起着重要的作用调节细胞增殖、细胞死亡和组织内稳态。已经被证明能够促进生存吗通过调节多种细胞的表达抗凋亡蛋白Bcl2。表明intra-nuclear PTHrP积累CFK2 (PTH1R积极)和27 m21 (PTH1R消极的)condrogenic细胞促进他们的生存关闭核糖体生物起源和促进静止。野生型PTHrP和检查的作用不能把到的变异形式在保护细胞免受TNFalpha-induced核细胞凋亡。有效地阻止外在途径抑制肿瘤坏死因子受体死亡的表达式域,激活和促进乳沟半胱天冬酶8。PTHrP机制actionon组件的外在途径,涉及到的一个区域蛋白质在nt。也抑制了内在的途径防止抗凋亡的交换pro-apoptotic线粒体蛋白质膜,从而保持其完整性和防止caspase-activating的释放因素进入胞液。mitochondrial-related活动有点延迟和更有效地调节了PTHrP比M1PTHrP,表明一种间接可能需要的作用机制一个完整的nt的存在。

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