Kannan Ram, Sreekumar Parameswaran G, Hinton David R
Beckman Macular Research Center, Doheny Eye Institute, Los Angeles, CA, United States.
Beckman Macular Research Center, Doheny Eye Institute, Los Angeles, CA, United States.
Biochim Biophys Acta. 2016 Jan;1860(1 Pt B):258-68. doi: 10.1016/j.bbagen.2015.05.016. Epub 2015 May 27.
αA- and αB crystallins are principal members of the small heat shock protein family and elicit both a cell protective function and a chaperone function. α-Crystallins have been found to be prominent proteins in normal and pathological retina emphasizing the importance for in-depth understanding of their function and significance.
Retinal pigment epithelial cells (RPE) play a vital role in the pathogenesis of age-related macular degeneration (AMD). This review addresses a number of cellular functions mediated by α-crystallins in the retina. Prominent expression of αB crystallin in mitochondria may serve to protect cells from oxidative injury. αB crystallin as secretory protein via exosomes can offer neuroprotection to adjacent RPE cells and photoreceptors. The availability of chaperone-containing minipeptides of αB crystallin could prove to be a valuable new tool for therapeutic treatment of retinal disorders.
α-Crystallins are expressed in cytosol and mitochondria of RPE cells and are regulated during oxygen-induced retinopathy and during development. α-Crystallins protect RPE from oxidative-and ER stress-induced injury and autophagy. αB-Crystallin is a modulator of angiogenesis and vascular endothelial growth factor. αB Crystallin is secreted via exosomal pathway. Minichaperone peptides derived from αB Crystallin prevent oxidant induced cell death and have therapeutic potential.
Overall, this review summarizes several novel properties of α-crystallins and their relevance to maintaining normal retinal function. In particular, the use of α-crystallin derived peptides is a promising therapeutic strategy to combat retinal diseases such as AMD. This article is part of a Special Issue entitled Crystallin biochemistry in health and disease.
αA-晶体蛋白和αB-晶体蛋白是小分子热休克蛋白家族的主要成员，具有细胞保护功能和伴侣功能。已发现α-晶体蛋白是正常和病理性视网膜中的重要蛋白质，这凸显了深入了解其功能和意义的重要性。
视网膜色素上皮细胞（RPE）在年龄相关性黄斑变性（AMD）的发病机制中起重要作用。本综述探讨了α-晶体蛋白在视网膜中介导的多种细胞功能。αB-晶体蛋白在线粒体中的显著表达可能有助于保护细胞免受氧化损伤。作为通过外泌体分泌的蛋白质，αB-晶体蛋白可为相邻的RPE细胞和光感受器提供神经保护。含有αB-晶体蛋白伴侣的小肽可能成为治疗视网膜疾病的有价值新工具。
α-晶体蛋白在RPE细胞的细胞质和线粒体中表达，并在氧诱导的视网膜病变和发育过程中受到调节。α-晶体蛋白保护RPE免受氧化应激和内质网应激诱导的损伤以及自噬。αB-晶体蛋白是血管生成和血管内皮生长因子的调节剂。αB-晶体蛋白通过外泌体途径分泌。源自αB-晶体蛋白的小伴侣肽可预防氧化剂诱导的细胞死亡并具有治疗潜力。
总体而言，本综述总结了α-晶体蛋白的几种新特性及其与维持正常视网膜功能的相关性。特别是，使用α-晶体蛋白衍生肽是对抗诸如AMD等视网膜疾病的有前景的治疗策略。本文是名为“健康与疾病中的晶体蛋白生物化学”的特刊的一部分。
