提起腦缺氧,、心缺血,、急性胰腺炎,、動脈粥樣硬化等疾病，從醫(yī)學(xué)的籠統(tǒng)意義上說,，它們都是由細(xì)胞壞死引起的疾病,。近日，廈門大學(xué)生命科學(xué)學(xué)院韓家淮教授課題組的一項研究表明,，存在于人體內(nèi)的一種名為RIP3的蛋白激酶是將細(xì)胞凋亡轉(zhuǎn)換成細(xì)胞壞死的分子“開關(guān)”,，通過調(diào)控這個開關(guān)，就可以調(diào)控細(xì)胞死亡方式,。這一發(fā)現(xiàn),，被認(rèn)為為臨床治療與細(xì)胞壞死的相關(guān)疾病提供了新的思路和方向。
6月4日出版的美國《科學(xué)》雜志以長篇研究報告的形式在線刊登了這項最新研究成果,。
細(xì)胞凋亡和細(xì)胞壞死是細(xì)胞死亡的兩種方式,。韓家淮介紹說，前者是細(xì)胞自發(fā)的生物學(xué)過程，死亡細(xì)胞遵循體積收縮,、染色質(zhì)濃縮,、核塌陷等一系列的程序，一般情況下,，這種死亡方式不會引起炎癥反應(yīng),，是正常的細(xì)胞死亡；后者則是因病理（如物理性或化學(xué)性的損害因子及缺氧與營養(yǎng)不良等）而產(chǎn)生的被動死亡,，通常意義上,，這種細(xì)胞死亡方式會導(dǎo)致炎癥反應(yīng)，而炎癥正是導(dǎo)致包括癌癥在內(nèi)的多種疾病產(chǎn)生的“罪魁禍?zhǔn)?rdquo;,，所以說這種方式是細(xì)胞的非正常死亡,。
長期以來，人們對細(xì)胞凋亡的認(rèn)識已經(jīng)較為清楚,，而細(xì)胞壞死的分子機(jī)制以及細(xì)胞凋亡與細(xì)胞壞死如何相互轉(zhuǎn)換在科學(xué)界卻仍然是個謎,。該課題組經(jīng)過近六年的研究發(fā)現(xiàn)，存在于人體內(nèi)的一種名為RIP3的蛋白激酶通過調(diào)節(jié)能量代謝,，可以將腫瘤壞死因子誘導(dǎo)的細(xì)胞凋亡轉(zhuǎn)換為細(xì)胞壞死,。簡言之，該蛋白激酶是細(xì)胞凋亡與壞死之間相互轉(zhuǎn)換的一個分子“開關(guān)”,，它通過調(diào)節(jié)能量代謝,，會影響細(xì)胞選擇不同的死亡方式。
韓家淮說,，這一發(fā)現(xiàn)的啟示意義在于,，如果我們能夠有效抑制RIP3的活性，就能在一定程度上抑制細(xì)胞死亡,，對那些由細(xì)胞死亡導(dǎo)致的相關(guān)疾病就可能起到治療,、防御或減輕的作用。
“但一般而言,，基礎(chǔ)研究要比應(yīng)用研究前置10至20年”,，談及這一成果的應(yīng)用前景，韓家淮說,，“要真正研發(fā)出抑制這種蛋白激酶的藥物,，還要經(jīng)歷尋找抑制物、修飾抑制物,、動物實驗,、臨床實驗等漫長而艱苦的環(huán)節(jié)和過程”。（生物谷Bioon.com）
生物谷推薦原始出處：
Science June 4, 2009 DOI: 10.1126/science.1172308
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.
* To whom correspondence should be addressed.
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.
