EPOR/CD131-mediated attenuation of rotenone-induced retinal degeneration is associated with upregulation of autophagy genes

IF 0.2 Q4 MEDICINE, GENERAL & INTERNAL

Bulletin of Russian State Medical University Pub Date : 2022-08-01 DOI:10.24075/brsmu.2022.040

VO Soldatov, M. Pokrovskiy, O. Puchenkova, NS Zhunusov, A. Krayushkina, AV Grechina, M. Soldatova, K. Lapin, OYu Bushueva

引用次数: 0

Abstract

Mitochondrial dysfunction is a key driver of neurodegeneration. This study aimed to evaluate the protective potential of EPOR/CD131 (heterodimeric erythropoietin receptor) stimulation in the neurodegeneration caused by rotenone-induced mitochondrial dysfunction. The effects of erythropoietin (EPO) and an EPO mimetic peptide pHBSP were assessed using in vivo and in vitro models. Single injections of 10 µg/kg EPO or 5 µg/kg pHBSP significantly alleviated the degeneration of ganglion cells of the retina in a rotenone-induced retinopathy in rats (p < 0.05). Consistently, in vitro exposure of rotenone-treated murine primary neuroglial cultures to 500 nM EPO or pHBSP significantly rescued the survival of the cells (p < 0.005). The observed enhancement of LC3A, ATG7, Beclin-1, Parkin and BNIP3 mRNA expression by EPOR/CD131 agonists implicates the autophagy and mitophagy activation as a plausible mitoprotective mechanism.

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EPOR/CD131介导的鱼藤酮诱导的视网膜变性的减弱与自噬基因的上调有关

线粒体功能障碍是神经退行性变的关键驱动因素。本研究旨在评估EPOR/CD131（异二聚红细胞生成素受体）刺激对鱼藤酮诱导的线粒体功能障碍引起的神经退行性变的保护作用。使用体内和体外模型评估红细胞生成素（EPO）和EPO模拟肽pHBSP的作用。在鱼藤酮诱导的大鼠视网膜病变中，单次注射10µg/kg EPO或5µg/kg pHBSP可显著减轻视网膜神经节细胞的退化（p<0.05）。一致地，在体外将鱼藤酮处理的鼠原代神经胶质细胞培养物暴露于500 nM EPO或pHBSP显著挽救了细胞的存活（p<0.05），EPOR/CD131激动剂的Beclin-1、Parkin和BNIP3mRNA表达暗示自噬和线粒体自噬激活是一种可能的线粒体保护机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bulletin of Russian State Medical University MEDICINE, GENERAL & INTERNAL-

CiteScore

0.80

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0.00%

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期刊介绍： Bulletin of Russian State Medical University (Bulletin of RSMU, ISSN Print 2500–1094, ISSN Online 2542–1204) is a peer-reviewed medical journal of Pirogov Russian National Research Medical University (Moscow, Russia). The original language of the journal is Russian (Vestnik Rossiyskogo Gosudarstvennogo Meditsinskogo Universiteta, Vestnik RGMU, ISSN Print 2070–7320, ISSN Online 2070–7339). Founded in 1994, it is issued once every two months publishing articles on clinical medicine and medical and biological sciences, first of all oncology, neurobiology, allergy and immunology, medical genetics, medical microbiology and infectious diseases. Every issue is thematic. Deadlines for manuscript submission are announced in advance. The number of publications on topics in spite of the issue topic is limited. The journal accepts only original articles submitted by their authors, including articles that present methods and techniques, clinical cases and opinions. Authors must guarantee that their work has not been previously published elsewhere in whole or in part and in other languages and is not under consideration by another scientific journal. The journal publishes only one review per issue; the review is ordered by the editors.