Hou Q, Cymbalyuk E, Hsu S-C, Xu M, Hsu Y-T
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
Apoptosis. 2003 Dec;8(6):617-29. doi: 10.1023/A:1026187526113.
Bcl-2 and Bcl-X(L) are pro-survival members of the Bcl-2 family. These proteins have been shown to antagonize the pro-apoptotic activity of Bax and promote cell survival through blocking Bax translocation from the cytosol to mitochondria and by preventing the release of cytochrome c. However, it has been recently reported that transiently expressed Bcl-2 unexpectedly leads to significant cell toxicity. To study this intriguing phenomenon, we have carried out further analyses into the properties of transiently expressed Bcl-2. We found that various isoforms of human and different species of Bcl-2 were equally capable of inducing apoptosis. In addition, we discovered that transient expression of Bcl-2, unlike its pro-survival homolog Bcl-X(L), can lead to the release of cytochrome c from mitochondria and that the resulting cell death can be inhibited by caspase and calpain inhibitors. Moreover, we have shown that unlike the pro-apoptotic protein Bid, the toxicity associated with the transient expression of Bcl-2 occurs independent of the activity of the endogenous Bax. Finally, we found that in spite of its intrinsic toxicity, transiently expressed Bcl-2 is fully capable of blocking the ectopically expressed Bax from localizing to mitochondria. Taken together, these studies demonstrate that transiently expressed Bcl-2 displays opposing functional properties.
Bcl-2和Bcl-X(L)是Bcl-2家族的促生存成员。这些蛋白质已被证明可拮抗Bax的促凋亡活性，并通过阻止Bax从细胞质转运至线粒体以及防止细胞色素c的释放来促进细胞存活。然而，最近有报道称，瞬时表达的Bcl-2出人意料地导致显著的细胞毒性。为了研究这一有趣的现象，我们对瞬时表达的Bcl-2的特性进行了进一步分析。我们发现，人类的各种异构体以及不同物种的Bcl-2都同样能够诱导细胞凋亡。此外，我们发现，与它的促生存同源物Bcl-X(L)不同，Bcl-2的瞬时表达可导致细胞色素c从线粒体释放，并且由此产生的细胞死亡可被半胱天冬酶和钙蛋白酶抑制剂抑制。此外，我们还表明，与促凋亡蛋白Bid不同，与Bcl-2瞬时表达相关的毒性与内源性Bax的活性无关。最后，我们发现，尽管瞬时表达的Bcl-2具有内在毒性，但它完全能够阻止异位表达的Bax定位于线粒体。综上所述，这些研究表明，瞬时表达的Bcl-2表现出相反的功能特性。
