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去甲肾上腺素递质代谢产物产生自由基并激活线粒体通透性转换:一种DOPEGAL诱导凋亡的机制。

Norepinephrine transmitter metabolite generates free radicals and activates mitochondrial permeability transition: a mechanism for DOPEGAL-induced apoptosis.

作者信息

Burke W J, Kristal B S, Yu B P, Li S W, Lin T S

机构信息

Department of Neurology, Veterans Affairs Medical Center and Saint Louis University Medical School, St. Louis, MO 63110, USA.

出版信息

Brain Res. 1998 Mar 23;787(2):328-32. doi: 10.1016/s0006-8993(97)01488-1.

DOI:10.1016/s0006-8993(97)01488-1
PMID:9518674
Abstract

3,4-Dihydroxyphenylglycolaldehyde (DOPEGAL) is the monoamine oxidase A metabolite of norepinephrine (NE) and epinephrine. DOPEGAL, but neither NE nor its other metabolites induces apoptosis in differentiated PC-12 cells by an unknown mechanism. To study the mechanism of DOPEGAL-induced apoptosis, we tested DOPEGAL and NE for their capacity to generate free radicals and to induce mitochondrial permeability transition (PT). Results show that DOPEGAL but not NE forms reactive free radical intermediates under oxidative stress and enhances Ca2+-mediated induction of the mitochondrial PT. Linkage of these events to apoptosis is described. Implications for degenerative diseases are discussed.

摘要

3,4-二羟基苯乙醇醛(DOPEGAL)是去甲肾上腺素(NE)和肾上腺素的单胺氧化酶A代谢产物。DOPEGAL可通过未知机制诱导分化的PC-12细胞凋亡,而NE及其其他代谢产物均无此作用。为研究DOPEGAL诱导凋亡的机制,我们检测了DOPEGAL和NE产生自由基及诱导线粒体通透性转换(PT)的能力。结果显示,在氧化应激条件下,DOPEGAL而非NE形成反应性自由基中间体,并增强Ca2+介导的线粒体PT诱导。描述了这些事件与凋亡的关联。讨论了其对退行性疾病的意义。

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