期刊
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
卷 38, 期 6, 页码 2207-2218出版社
KARGER
DOI: 10.1159/000445576
关键词
Diabetic retinopathy; Nmnat1; Retinal ganglion cell; MAPK signaling
资金
- National Natural Science Foundation of China [81371055]
- National clinical key construction project [(2012) 649]
- Medical Science and Technology Development Project Fund of Nanjing [ZKX 12047]
Background/Aims: Retinal neurodegeneration is an early event in the pathological process of diabetic retinopathy (DR). Retinal ganglion cell (RGC) injury is an important pathological feature during neurodegenerative process. Protecting RGCs from high glucose-induced injury is a promising strategy for delaying or hindering diabetes mellitus-related retinal neuropathy. This study aims to investigate the role of Nmnatl, an enzyme which catalyzes a key step in the biosynthesis of nicotinamide adenine dinucleotide (NAD), in high glucose-induced RGC injury. Methods: Western blot and immunofluorescence analysis was conducted to detect Nmnatl expression pattern in the retina and RGC-5 cell. MTT assay, Hoechst staining, trypan blue staining, and calcein-AM/ propidium iodide (PI) staining was conducted to determine the effect of Nmnatl knockdown on RGC-5 cell function. Microarray and bioinformatics analysis was conducted to identify potential signaling pathways affected by Nmnatl knockdown. Pharmacological intervention, molecular intervention, and in vitro experiments were conducted to reveal molecular mechanism of Nmnatl-mediated protective effect on RGC-5 cell function. Results: Nmnatl is constitutively expressed in retina and RGC-5 cells. Nmnatl knockdown aggravates RGC injury, and accelerates the development of RGC-5 cell apoptosis upon high glucose stress. MAPK signaling is the primary signaling pathway affected by Nmnatl knockdown. Under high glucose stress. Nmnatl knockdown leads to p38-MAPK signaling inactivation. p38-MAPK pathway inhibitor strongly blocks Nmnatl-mediated protective effect on RGC-5 cell function. Conclusion: Nmnatl protects RGC against high glucose-induced injury via p38-MAPK signaling pathway. Nmnatl may serve as a neuroprotective target for diabetes mellitus-related retinal neuropathy. (C) 2016 The Author(s) Published by S. Karger AG, Basel
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