厦大韩家淮《Science》解析细胞凋亡坏死开关

　　

生物通报道，厦门大学生命科学院细胞生物学与肿瘤细胞工程教育部重点实验室在最新的Science在线版发表研究细胞凋亡-细胞坏死生物开关研究成果，RIP3, an Energy Metabolism Regulator that Switches TNF-Induced Cell Death from Apoptosis to Necrosis。

 

文章通讯作者是来自厦门大学生命科学院的****特聘教授韩家淮，2007年从Scripps研究所全职回国，短短1年多的时间在厦大完成了新的研究，取得新的成绩。

 

目前，生物通记者已经联系上韩家淮教授，敬请期待专访文章。

 

细胞坏死（necrosis）是一个由肿瘤坏死因子TNF或其他细胞因子介导的死亡受体诱导的生物学过程，细胞坏死与细胞凋亡的启动机制一直不明。在本研究中，韩家淮教授实验室鉴定了一种RIP3蛋白，该蛋白是细胞凋亡与细胞坏死的生物开关。

 

研究小组发现NIH3T3细胞中，蛋白激酶RIP3是启动细胞凋亡或是细胞坏死的重要分子开关，并且在其他细胞中，细胞坏死程序也需要有RIP3的参与。RIP3不会影响RIP1介导的细胞凋亡，但是却会影响RIP1介导的细胞坏死过程，RIP3能通过半胱天冬酶抑制剂zVAD增强细胞坏死作用。RIP3通过激活关键代谢酶的活性调节TNF介导的活性氧簇产量，活性氧簇能促进RIP3诱导细胞坏死。

 

这些结果表明，细胞在受到死亡刺激后产生的应激能量代谢的调节对细胞选择自我凋亡和细胞坏死具有重要的意义。RIP3是调控细胞凋亡或是细胞坏死的生物学开关。

（生物通 小茜）

 

生物通推荐原文检索：RIP3, an Energy Metabolism Regulator that Switches TNF-Induced Cell Death from Apoptosis to Necrosis

 

Duan-Wu Zhang 1, Jing Shao 1, Juan Lin 1, Na Zhang 1, Bao-Ju Lu 2, Sheng-Cai Lin 1, Meng-Qiu Dong 2, Jiahuai Han 1*

1 The Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.

2 The National Institute of Biological Sciences, Beijing, China.

 

Necrosis can be induced by stimulating death receptors with tumor necrosis factor (TNF) or other agonists; however, the underlying mechanism differentiating necrosis from apoptosis is largely unknown. We identified the protein kinase RIP3 as a molecular switch between TNF-induced apoptosis and necrosis in NIH3T3 cells, and found that RIP3 was required for necrosis in other cells. RIP3 did not affect RIP1-mediated apoptosis, but was required for RIP1-mediated necrosis and the enhancement of necrosis by the caspase inhibitor zVAD. By activating key enzymes of metabolic pathways, RIP3 regulated TNF-induced reactive oxygen species production, which partially accounts for RIP3’s ability to promote necrosis. Our data suggest that modulation of energy metabolism in response to death stimuli has an important role in the choice between apoptosis and necrosis.