Programmed necrosis - a new mechanism of steroidogenic luteal cell death and elimination during luteolysis in cows.
Programmed necrosis - a new mechanism of steroidogenic luteal cell death and elimination during luteolysis in cows.
复制标题
DOI：
10.1038/srep38211
复制
发表时间：
2016-11-30
影响因子：
4.6
通讯作者：
Skarzynski DJ
中科院分区：
文献类型：
--
作者：
Hojo T;Siemieniuch MJ;Lukasik K;Piotrowska-Tomala KK;Jonczyk AW;Okuda K;Skarzynski DJ
程序性坏死（坏死性凋亡）是程序性细胞死亡的一种替代形式，受受体相互作用蛋白激酶（RIPK）1和3依赖性调节，但是一种半胱天冬酶（CASP）非依赖性途径。在本研究中，为了确定坏死性凋亡是否参与了牛的结构性黄体溶解，我们研究了RIPK 1和RIPK 3在整个发情周期、前列腺素F2α（PGF）诱导的牛黄体（CL）黄体溶解期间以及用选定的黄体溶解因子处理后培养的黄体类固醇生成细胞（LSC）中的表达。此外，还评价了RIPK 1抑制剂（necrostatin-1，Nec-1; 50 μM）对细胞活力、孕酮分泌、凋亡相关因子和RIPK表达的影响。RIPK 1和RIPK 3在自发性黄体溶解和前列腺素F诱导的黄体溶解中表达均增加（P < 0.05）。在培养的LSC中，肿瘤坏死因子α（TNF; 2.3 nM）与干扰素γ（IFNG; 2.5 nM）联合作用可上调RIPK 1 mRNA和蛋白表达（P < 0.05）。TNF + IFNG可上调RIPK 3 mRNA表达（P < 0.05），但对RIPK 3蛋白表达无明显影响。尽管Nec-1阻止TNF + IFNG诱导的细胞死亡（P < 0.05），但其不影响CASP 3和CASP 8的表达。Nec-1可降低RIPK 1和RIPK 3蛋白表达（P < 0.05）。这些发现表明，RIPKS依赖性坏死性凋亡是一种有效的机制，负责牛结构性黄体溶解诱导的促炎细胞因子。
Programmed necrosis (necroptosis) is an alternative form of programmed cell death that is regulated by receptor-interacting protein kinase (RIPK) 1 and 3-dependent, but is a caspase (CASP)-independent pathway. In the present study, to determine if necroptosis participates in bovine structural luteolysis, we investigated RIPK1 and RIPK3 expression throughout the estrous cycle, during prostaglandin F2α (PGF)-induced luteolysis in the bovine corpus luteum (CL), and in cultured luteal steroidogenic cells (LSCs) after treatment with selected luteolytic factors. In addition, effects of a RIPK1 inhibitor (necrostatin-1, Nec-1; 50 μM) on cell viability, progesterone secretion, apoptosis related factors and RIPKs expression, were evaluated. Expression of RIPK1 and RIPK3 increased in the CL tissue during both spontaneous and PGF-induced luteolysis (P < 0.05). In cultured LSCs, tumor necrosis factor α (TNF; 2.3 nM) in combination with interferon γ (IFNG; 2.5 nM) up-regulated RIPK1 mRNA and protein expression (P < 0.05). TNF + IFNG also up-regulated RIPK3 mRNA expression (P < 0.05), but not RIPK3 protein. Although Nec-1 prevented TNF + IFNG-induced cell death (P < 0.05), it did not affect CASP3 and CASP8 expression. Nec-1 decreased both RIPK1 and RIPK3 protein expression (P < 0.05). These findings suggest that RIPKs-dependent necroptosis is a potent mechanism responsible for bovine structural luteolysis induced by pro-inflammatory cytokines.
登录
查看更多内容
影响因子：
1.8
作者：
Korzekwa, Anna J.;Okuda, Kiyoshi;Skarzynski, Dariusz J.
通讯作者：
Skarzynski, Dariusz J.
影响因子：
3.6
作者：
Friedman, A;Weiss, S;Meidan, R
通讯作者：
Meidan, R
影响因子：
64.5
作者：
Cho YS;Challa S;Moquin D;Genga R;Ray TD;Guildford M;Chan FK
通讯作者：
Chan FK
影响因子：
1.7
作者：
Korzekwa, A. J.;Jaroszewski, J. J.;Skarzynski, D. J.
通讯作者：
Skarzynski, D. J.
影响因子：
14.8
作者：
Degterev, Alexei;Hitomi, Junichi;Yuan, Junying
通讯作者：
Yuan, Junying