Receptor interacting protein kinases-dependent necroptosis as a new, potent mechanism for elimination of the endothelial cells during luteolysis in cow
Receptor interacting protein kinases-dependent necroptosis as a new, potent mechanism for elimination of the endothelial cells during luteolysis in cow
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DOI：
10.1016/j.theriogenology.2019.01.035
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发表时间：
2019-04-01
期刊：
影响因子：
2.8
通讯作者：
Skarzynski, Dariusz J.
中科院分区：
文献类型：
--
作者：
Hojo, Takuo;Piotrowska-Tomala, Katarzyna K.;Skarzynski, Dariusz J.
坏死性凋亡是一种由受体相互作用蛋白激酶（RIPK）1和3依赖性调节的程序性细胞死亡的替代形式。在本研究中，为了阐明黄体内皮细胞（LEC）的坏死性凋亡是否参与并促成牛黄体溶解，我们研究了RIPK 1和RIPK 3在黄体组织中的定位及其在用选定的免疫因子-前列腺素F2 α（PGF）的黄体溶解作用的介质处理后培养的LEC中的表达。此外，研究了肿瘤坏死因子α（TNF; 2.3 nM）与干扰素γ（IFNG; 2.5 nM）和/或一氧化氮供体- NONOate（100 μ M）组合对培养的LEC中的活力和CASP 3活性的影响。此外，评价了RIPK 1抑制剂（necrostatin-1，Nec-1; 50 μ M）对RIPK和CASP表达的影响。检测RIPK 1和RIPK 3蛋白在培养的LEC中的定位。在培养的LEC中，TNF + IFNG在12 h、PGF（1 μ M）或NONOate在24 h分别上调RIPKs mRNA的表达（P < 0.05）。虽然NONOate降低了细胞活力，但它阻止了培养的LEC中TNF + IFNG刺激的CASP 3活性。Nec-1抑制TNF + IFNG诱导的RIPK 1和CASP 3 mRNA表达，并抑制RIPK 3 mRNA表达。提示TNF + IFNG、PGF或NO诱导的RIPKs依赖性坏死性凋亡可能是导致牛CL退化过程中LECs细胞死亡和黄体毛细血管消失的重要机制。(C)2019爱思唯尔公司All rights reserved.
Necroptosis is an alternative form of programmed cell death regulated by receptor-interacting protein kinase (RIPK) 1 and 3-dependent. In the present study, to clarify if necroptosis in luteal endothelial cells (LECs) participates and contributes for bovine luteolysis, we investigated RIPK1 and RIPK3 localization in luteal tissue and their expression in cultured LECs after treatment with selected immune factors - mediators of luteolytic action of prostaglandin F2 alpha (PGF). In addition, effects of tumor necrosis factor alpha (TNF; 2.3 nM) in combination with interferon gamma (IFNG; 2.5 nM), and/or nitric oxide donor - NONOate (100 mu M) on viability and CASP3 activity in the cultured LECs were investigated. Furthermore, effects of a RIPK1 inhibitor (necrostatin-1, Nec-1; 50 mu M) on RIPKs and CASPs expression, were evaluated. Localization of RIPK1 and RIPK3 protein in the cultured LECs were determined. In cultured LECs, expression of RIPKs mRNA were up-regulated by TNF + IFNG at 12 h, and by PGF (1 mu M) or NONOate at 24 h, respectively (P < 0.05). Although NONOate decreased cell viability, it prevented TNF + IFNG-stimulated CASP3 activity in cultured LECs. Nec-1 prevented TNF + IFNG-induced RIPK1 and CASP3 mRNA expression at 12 h and prevented RIPK3 mRNA expression. These findings suggest that RIPKs-dependent necroptosis which are induced by TNF + IFNG, PGF or NO could be potent mechanism responsible for LECs cell death and disappearance of luteal capillaries in regressing bovine CL. (C) 2019 Elsevier Inc. All rights reserved.