| Summary: | 碩士 === 國立臺灣海洋大學 === 生物科技研究所 === 99 === In central nervous system, oxidative stress may contribute to the neuronal degeneration in neurodegenerative diseases. Microglia activated by inflammatory stimulation may release nitric oxide (NO), which induces BNIP3 (Bcl-2/adenovirus E1B 19-kD interaction protein 3) expression observed in macrophages and enterocytes. BNIP3 is a pro-cell-death Bcl-2 family protein which contains a transmembrane domain at C terminal of BNIP3. Accroding to previous research, the majority of Bcl-2 family members are regulated post-translationally, such as phosphorylation, and BNIP3 is indeed regulated by phosphorylation on the monomeric and dimeric form, this modification are related to BNIP3 induced cell death.
In this study, SNAP, a NO donor, and AG490, a tyrosine kinase inhibitor, we were used to treat Neuro-2a (N2a) cells. We found that NO- induced Neuron-2a (N2a) cell death was regulated by BNIP3, and AG490 promoted the cell death. The NO induced cell death was through mitochondria dysfunction and autophagy. To investigate tyrosine phosphorylation of BNIP3, we constructed a mutant that mimic tyrosine phosphorylation of BNIP3 (BNIP3- Y175D, Y92D, Y33D；BNIP3-DDD). N2a cell transfected with BNIP3-DDD reduced NO-induced mito- chondria aggregation. The expression of BNIP3-DDD decreased compared with the cells transfected with BNIP3. We found that proteasome may degrade tyrosine phoshprylated BNIP3 and decrease the pro-cell-death activity of BNIP3.
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