Regulation of Apoptosis by Arachidonic Acid and the Adenovirus 14.7K Protein

ROS;adenovirus 14.7K protein;arachidonic acid;calcium;mitochondria;fatty acids;apoptosis;TNF

Maia, Rita de Cassia Carvalho ; Scott M. Laster, Committee Chair,Amy Grunden, Committee Member,Hosni Hassan, Committee Member,Tim Petty, Committee Member,Maia, Rita de Cassia Carvalho ; Scott M. Laster ; Committee Chair ; Amy Grunden ; Committee Member ; Hosni Hassan ; Committee Member ; Tim Petty ; Committee Member

University:North Carolina State University

关键词: ROS;    adenovirus 14.7K protein;    arachidonic acid;    calcium;    mitochondria;    fatty acids;    apoptosis;    TNF;   

Others  :  https://repository.lib.ncsu.edu/bitstream/handle/1840.16/3646/etd.pdf?sequence=1&isAllowed=y

美国|英语

来源: null

【 摘 要 】

In this study we explored several aspects of the apoptotic response induced by the cytokine tumor necrosis factor (TNF). One set of experiments addressed the role played by arachidonic acid in the apoptotic signaling pathway. The release of this fatty acid during TNF-induced apoptosis was reported over twenty year ago, however, its role in the apoptotic process has remained enigmatic. The results of our experiments suggest that arachidonic acid is critical during apoptosis for inactivation of mitochondria. Arachidonic acid caused loss of mitochondrial transmembrane potential and inhibited mitochondrial respiration at complexes I and II. Arachidonic acid was also found to elevate levels of intracellular calcium; however, it is unlikely that this response is related to its pro-apoptotic activity since inhibition of the calcium response did not inhibit apoptosis. In a second set of experiments we investigated the anti-apoptotic activity of the adenovirus 14.7K gene product. Our experiments revealed that the 14.7 K protein inhibits the TNF-induced production of reactive oxygen species (ROS). This effect was selective for TNF; the 14.7K protein did not block ROS production following treatment with LPS, arachidonic acid, melphalan, or menadione. Since ROS are produced early in the apoptotic signaling pathway, our results suggest the 14.7K protein inhibits apoptosis by interfering with TNFdependent apoptotic signaling.