Puma is a dominant regulator of oxidative stress induced Bax activaion and neuronal apoptosis (J Neurosci, 2007, 27:12980-12999)

報告日期: 2008/06/06
報告時間: 15:10/16:00
報告學生: 趙詠梅
講評老師: 李學德


Puma Is a Dominant Regulator of Oxidative Stress Induced Bax Activation and Neuronal Apoptosis

The Journal of Neuroscience, 2007, 27:12989-12999


Speaker: 趙詠梅

Commentator: Dr. 李學德

Time: 2008/06/06 pm 5:10~6:00

Place: R602



In the central nervous system, oxidative stress of an elevated tissue level of the reactive oxygen species has been demonstrated to play an important role in degenerative disorders, such as ischemic stroke, Alzheimer’s disease (AD), Huntington’s disease (HD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). The neurons in stroke and neurodegenerative conditions die through a process known as apoptosis, which can be triggered by oxidative stress. The Bcl-2 protein family consists of proapoptotic and antiapoptotic members. The proapoptotic family members control the permeability of mitochondrial membrane during apoptosis. When Bcl-2-associated X protein (Bax) and Bcl-2 homologous antagonist killer (Bak) target the mitochondria, the permeability of the outer mitochondrial membrane is increased. The process leads to the release of apoptogenic factor cytochrome c and subsequent manifestation of apoptotic cell death. Expression and activity of Bax/Bak are regulated by the Bcl-2 homology 3 (BH3)-domain-only proteins. In this study, the authors demonstrated that oxidative stress had induced the expression of BH3 member of Bim, Noxa, and Puma. Among these molecules, only Puma-deficient neurons are resistant to the induction of apoptosis by multiple oxidative stressors. Furthermore, activation of Bax is dominantly regulated by Puma and is required for oxidative stress induced cell death. These results led the authors to conclude that Puma is an important regulator of Bax activation and neuronal apoptosis induced by oxidative stress, and that Puma may be a key therapeutic target for neuroprotection.




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