Bcl-xL as a Critical Apoptosis Antagonist in Hepatocytes and Hepatocellular Carcinoma

摘要: Bcl-xL, an anti-apoptotic member of the Bcl-2 family, has been generally thought to be involved in regulation apoptosis liver, because this molecule tends upregulated during liver regeneration, as well certain types injury. We employed a Cre/loxP conditional knockout model and found that deletion bcl-x gene resulted accelerated hepaocytes vivo, formally proving critical role maintaining hepatocyte integrity. Furthermore, Bcl-xL may play important hepatocarcinogenesis, one-third human hepatocellular carcinoma (HCC) tissues showed increased expression its knockdown by antisense oligonueleotide stimulated hepatoma cells response cellular stresses, such serum starvation, p53 activation, staurosporine treatment. It was also post-translationally modified deamidation loop domain tissues; deamidated is major form normal tissues, whereas level lower than unmodified majority HCC tissues. As protein leads complete “loss function” antiapoptotic molecule, HCCs acquire resistance survival advantage suppressing deamidation, increasing Bcl-xL.