Neuroprotective role of erythropoietin by antiapoptosis in the retina.
Neuroprotective role of erythropoietin by antiapoptosis in the retina.
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DOI：
10.1002/jnr.22046
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发表时间：
2009-08-01
影响因子：
4.2
通讯作者：
Jahng, Wan Jin
中科院分区：
文献类型：
--
作者：
Chung, Hyewon;Lee, Hyunju;Lamoke, Folami;Hrushesky, William J. M.;Wood, Patricia A.;Jahng, Wan Jin
促红细胞生成素（EPO）刺激红细胞生成，部分是通过抑制红细胞前体细胞凋亡。EPO的红细胞生成作用是昼夜节律阶段依赖性的。光引起的视网膜损伤通过氧化机制发生，并表现为视网膜和视网膜色素上皮（RPE）细胞凋亡。视觉周期可能是昼夜节律协调的，作为有效保护视网膜免受光诱导的、氧依赖性的、自由基介导的损伤的有害影响的手段，特别是在一天中光线更强烈的时候。我们表明，视网膜表达的EPO及其受体（EPOR），以及随后的Janus激酶2（Jak2）磷酸化，每个紧密相连的特定时间后，氧化应激和预期的日常光照。这与针对日常光诱导的氧化介导的视网膜凋亡的生理保护一致。在体外，我们证实EPO保护RPE细胞免受光、高氧和过氧化氢诱导的视网膜细胞凋亡，并且这些刺激增加培养的RPE细胞中EPO和EPOR的表达。总之，这些数据支持EPO及其EPOR相互作用代表生理和病理光诱导的氧化损伤的重要视网膜屏障的前提。
Erythropoietin (EPO) stimulates red blood cell production, in part by inhibiting apoptosis of the red blood cell precursors. The erythropoietic effects of EPO are circadian stage dependent. Retinal injury due to light occurs through oxidative mechanisms and is manifest by retinal and retinal pigment epithelium (RPE) cells apoptosis. The visual cycle might be circadian coordinated as a means of effectively protecting the retina from the detrimental effects of light-induced, oxygen-dependent, free radical–mediated damage, especially at the times of day when light is more intense. We show that the retinal expression of EPO and its receptor (EPOR), as well as subsequent Janus kinase 2 (Jak2) phosphorylations, are each tightly linked to a specific time after oxidative stress and in anticipation of daily light onset. This is consistent with physiological protection against daily light-induced, oxidatively mediated retinal apoptosis. In vitro, we verify that EPO protects RPE cells from light, hyperoxia, and hydrogen peroxide–induced retinal cell apoptosis, and that these stimuli increase EPO and EPOR expression in cultured RPE cells. Together, these data support the premise that EPO and its EPOR interactions represent an important retinal shield from physiologic and pathologic light-induced oxidative injury.
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