All-trans-retinal induces Bax activation via DNA damage to mediate retinal cell apoptosis.
All-trans-retinal induces Bax activation via DNA damage to mediate retinal cell apoptosis.
复制标题
全反视网膜通过DNA损伤诱导视网膜细胞凋亡诱导BAX激活。
DOI：
10.1016/j.exer.2014.04.003
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发表时间：
2014-06
影响因子：
3.4
通讯作者：
Maeda, Tadao
中科院分区：
文献类型：
--
作者：
Sawada, Osamu;Perusek, Lindsay;Kohno, Hideo;Howell, Scott J.;Maeda, Akiko;Matsuyama, Shigemi;Maeda, Tadao
关键词：
目前的研究调查的细胞事件，触发激活的促凋亡Bcl-2相关的X蛋白（Bax）的视网膜细胞死亡诱导的全反式视网膜（atRAL）。使用ARPE-19细胞、661 W细胞、培养的神经视网膜和视网膜变性模型Abca 4 −/− Rdh 8 −/−小鼠，通过免疫化学和生物化学方法评估激活Bax的细胞事件，例如氧化应激和p53磷酸化引起的DNA损伤。通过药理学和遗传学方法检测了培养的神经视网膜中atRAL诱导的Bax活化。还通过药理学和生物化学方法评价了其他与肿瘤相关的细胞事件。在用atRAL孵育的ARPE-19细胞中，在Bax活化之前检测到8-OHdG（DNA损伤指示剂）的产生和p53在Ser 46处的磷酸化。光暴露于Abca 4 −/− Rdh 8 −/−小鼠也会在短期强光暴露和常规室内照明条件下引起上述事件。在培养的神经视网膜中，与Bax抑制肽一起孵育和Bax基因的缺失部分保护视网膜细胞免受atRAL毒性。坏死被证明不是atRAL介导的细胞死亡的主要途径。在体外，atRAL没有改变Bcl-2相互作用介质和Bcl-2表达水平。atRAL诱导的氧化应激导致DNA损伤，导致Bax被磷酸化的p53激活。这种级联反应与凋亡细胞死亡机制密切相关，而不是坏死。
The current study investigates the cellular events which trigger activation of proapoptotic Bcl-2-associated X protein (Bax) in retinal cell death induced by all-trans-retinal (atRAL). Cellular events which activate Bax, such as DNA damage by oxidative stress and phosphorylation of p53, were evaluated by immunochemical and biochemical methods using ARPE-19 cells, 661W cells, cultured neural retinas and a retinal degeneration model, Abca4−/−Rdh8−/− mice. atRAL-induced Bax activation in cultured neural retinas was examined by pharmacological and genetic methods. Other Bax-related cellular events were also evaluated by pharmacological and biochemical methods. Production of 8-OHdG, a DNA damage indicator, and the phosphorylation of p53 at Ser 46 were detected prior to Bax activation in ARPE-19 cells incubated with atRAL. Light exposure to Abca4−/−Rdh8−/− mice also caused the above mentioned events in conditions of short term intense light exposure and regular room lighting conditions. Incubation with Bax inhibiting peptide and deletion of the Bax gene partially protected retinal cells from atRAL toxicity in cultured neural retina. Necrosis was demonstrated not to be the main pathway in atRAL mediated cell death. Bcl-2-interacting mediator and Bcl-2 expression levels were not altered by atRAL in vitro. atRAL-induced oxidative stress results in DNA damage leading to the activation of Bax by phosphorylated p53. This cascade is closely associated with an apoptotic cell death mechanism rather than necrosis.
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影响因子：
4.8
作者：
Maeda, Akiko;Maeda, Tadao;Palczewski, Krzysztof
通讯作者：
Palczewski, Krzysztof
影响因子：
4.3
作者：
Bishayee, Kausik;Paul, Avijit;Khuda-Bukhsh, Anisur Rahman
通讯作者：
Khuda-Bukhsh, Anisur Rahman
影响因子：
7.2
作者：
Cottet, Sandra;Schorderet, Daniel F.
通讯作者：
Schorderet, Daniel F.
影响因子：
12.4
作者：
Hahn, P;Lindsten, T;Dunaief, JL
通讯作者：
Dunaief, JL
影响因子：
4.8
作者：
Chen, Yu;Okano, Kiichiro;Palczewski, Krzysztof
通讯作者：
Palczewski, Krzysztof