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2006年 生命科學與醫學獎

王曉東

為表彰他發現細胞按程序凋亡的生物化學基礎。細胞按程序凋亡是平衡細胞生成和防止癌的關鍵步驟。

 

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王曉東

貢獻

人體由上萬億個細胞組成。每天有上十億個細胞凋亡並由新生細胞所取代。細胞的生成和凋亡必須精確地平衡。如果細胞生成太多,器官就會長大成為癌,反之,器官將退化,引起如阿爾滋海默症這樣的病變。控制細胞生成的因子已經研究了許多年,並且已經了解得很多。相反,直到豪爾維玆揭示蛔虫有一個稱為細胞按程序凋亡,由基因決定的控制機制以前,人們認為細胞凋亡是無序的。雖然知道了這個現象,可是直到王曉東證明它是由細胞器─線粒體─執行的以前,細胞按程序凋亡的生物化學機制是不清楚的。過去,人們認為線粒體的功能只是一個能量發生器。

每一個有細胞核的動物細胞都有許多線粒體。線粒體是一個由膜組成的微小的結構,充滿了氧化食品和生成高能化合物的酶。當細胞按程序凋亡時,線粒體釋放觸發細胞凋亡的一些蛋白,其中之一是細胞色素C。長久以來,人們只知道細胞色素C是產能系統必要的成份。王曉東用了聰明的生物化學方法,證明由線粒體來的細胞色素 C 觸發一聯串反應,導致細胞核脫氧核糖核酸碎裂,細胞膜溶解以及凋亡的細胞被鄰近的清掃細胞所吞噬。為了遏制細胞色素C的自殺作用,細胞產生阻遏caspase活力的蛋白。王曉東證明線粒體釋放另外一種蛋白,使細胞凋亡得以完成。

 

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The human body is composed of 10 trillion cells. Each day billions of cells die and are replaced by fresh cells. The birth and death of cells must be perfectly balanced. If cell birth exceeds death, organs enlarge and cancer results. If death exceeds birth, organs degenerate, as in Alzheimer's disease. The factors controlling cell birth have been studied for many decades and much has been learned. In contrast, cell death was considered a random event until the studies of Horvitz in roundworms revealed a gene-determined control mechanism called programmed cell death. Although the phenomenon was recognized, the biochemical mechanism was obscure until Xiaodong Wang showed that the executioner is an internal organelle, the mitochondrion, which was previously thought to function only as an energy generator.

 

Every nucleated animal cell contains many mitochondria, which are tiny membrane-bound structures filled with enzymes that oxidize foodstuffs and generate high-energy chemicals. When a cell is programmed to die, the mitochondria release proteins that trigger cell death. One such protein, cytochrome C, was long known as an essential component of the energy-generating system. Using clever biochemical measurements, Wang showed that mitochondria-derived cytochrome C binds to a cytosolic protein, Apaf-1, thereby activating a protease called caspase-3. Activated caspase 3 triggers a cascade of reactions that lead to fragmentation of nuclear DNA, dissolution of the cell membrane, and engulfment of the dying cell by neighboring scavenger cells. Cells resist the suicidal action of cytochrome C by producing proteins called IAPs that block the caspase. Wang showed that mitochondria overcome this resistance by releasing another protein, Smac, which neutralizes the IAPs, permitting cell death to proceed to completion. Wang also discovered a mitochondria-derived nuclease that assists in the fragment of nuclear DNA.

 

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王曉東

王曉東 (Xiaodong Wang)

王曉東 (Xiaodong Wang) (1963年出生) 現在美國德州大學西南醫學中心任終身教授,並在著名的霍華德.休斯研究所擔任研究員。王教授1984年畢業於北京師範大學(生物學系),1991年取得美國德州大學西南醫學中心生物化學博士。2004年當選美國科學院院士。


2006年6月21日 香港

 

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2006年度邵逸夫生命科學與醫學獎講座

"How Do We Save Lives by Understanding Death?"由王曉東教授主講