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Osamu Sawada, Akiko Maeda, Shigemi Matsuyama, Tadao Maeda; Molecular events for Bax activation in retinal cell death induced by all-trans-retinal. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1779.
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Excess accumulation of all-trans-retinal (atRAL) after intense light exposure has been observed to cause apoptotic retinal cell death. Both oxidative stress and activation of the Bcl-2-associated X protein (Bax) have been implicated in atRAL induced cell death. However, a suitable relationship between these events remains unclear. The aim of this study is to seek molecular targets that are sensitive to oxidative stress in the retina, and subsequently cause retinal cell death via Bax activation.
Bax activation, phosphorylation of p53 at Ser46 which regulates the ability of p53 to induce apoptosis, and DNA damage by oxidative stress were evaluated after incubation with atRAL in ARPE19 cells using immunocytochemistry in vitro. Furthermore, these events were examined in retinas of Abca4-/-Rdh8-/- mice after intense light exposure or with aging using immunohistochemistry in vivo. Bax activation, phosphorylated-p53 at Ser46, and 8-hydroxy-2’-deoxyguanosine (8-OHdG), an indicator of oxidative DNA damage were monitored by anti-activated Bax antibody (6A7), anti-phosphorylated-p53 (Ser46) antibody, and anti-8-OHdG antibody, respectively.
Increased signal intensity indicates Bax activation, increased phosphorylatation of p53 at Ser46, and DNA damage after atRAL incubation in ARPE19 cells. Bax activation, phosphorylation of p53 at Ser46, and DNA damage were additionally found in retinas of Abca4-/-Rdh8-/- mice after light exposure and those of Abca4-/-Rdh8-/- mice at 6 months of age.
DNA damage caused by oxidative stress and the subsequent phosphorylation of p53 can trigger Bax activation in retinal cell death process induced by atRAL.
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