دورية أكاديمية
Vitamin B3, nicotinamide, enhances mitochondrial metabolism to promote differentiation of the retinal pigment epithelium.
| العنوان: | Vitamin B3, nicotinamide, enhances mitochondrial metabolism to promote differentiation of the retinal pigment epithelium. |
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| المؤلفون: | Hazim RA; Department of Ophthalmology and Stein Eye Institute, University of California, Los Angeles, California, USA., Paniagua AE; Department of Ophthalmology and Stein Eye Institute, University of California, Los Angeles, California, USA., Tang L; Department of Ophthalmology and Stein Eye Institute, University of California, Los Angeles, California, USA., Yang K; Department of Molecular and Medical Pharmacology, UCLA David Geffen School of Medicine, Los Angeles, California, USA., Kim KKO; Department of Molecular and Medical Pharmacology, UCLA David Geffen School of Medicine, Los Angeles, California, USA., Stiles L; Department of Molecular and Medical Pharmacology, UCLA David Geffen School of Medicine, Los Angeles, California, USA; Division of Endocrinology, Department of Medicine, UCLA David Geffen School of Medicine, Los Angeles, California, USA., Divakaruni AS; Department of Molecular and Medical Pharmacology, UCLA David Geffen School of Medicine, Los Angeles, California, USA., Williams DS; Department of Ophthalmology and Stein Eye Institute, University of California, Los Angeles, California, USA; Department of Neurobiology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA; Molecular Biology Institute, University of California, Los Angeles, California, USA; Brain Research Institute, University of California, Los Angeles, California, USA. Electronic address: dswilliams@ucla.edu. |
| المصدر: | The Journal of biological chemistry [J Biol Chem] 2022 Sep; Vol. 298 (9), pp. 102286. Date of Electronic Publication: 2022 Jul 20. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology |
| مواضيع طبية MeSH: | Cell Differentiation*/drug effects , Mitochondria*/genetics , Mitochondria*/metabolism , Niacinamide*/pharmacology , Retinal Pigment Epithelium*/cytology , Retinal Pigment Epithelium*/drug effects , Retinal Pigment Epithelium*/metabolism, Animals ; Cell Line ; Glucose/metabolism ; Humans ; Pyruvic Acid/metabolism |
| مستخلص: | In the mammalian retina, a metabolic ecosystem exists in which photoreceptors acquire glucose from the choriocapillaris with the help of the retinal pigment epithelium (RPE). While the photoreceptor cells are primarily glycolytic, exhibiting Warburg-like metabolism, the RPE is reliant on mitochondrial respiration. However, the ways in which mitochondrial metabolism affect RPE cellular functions are not clear. We first used the human RPE cell line, ARPE-19, to examine mitochondrial metabolism in the context of cellular differentiation. We show that nicotinamide induced rapid differentiation of ARPE-19 cells, which was reversed by removal of supplemental nicotinamide. During the nicotinamide-induced differentiation, we observed using quantitative PCR, Western blotting, electron microscopy, and metabolic respiration and tracing assays that (1) mitochondrial gene and protein expression increased, (2) mitochondria became larger with more tightly folded cristae, and (3) mitochondrial metabolism was enhanced. In addition, we show that primary cultures of human fetal RPE cells responded similarly in the presence of nicotinamide. Furthermore, disruption of mitochondrial oxidation of pyruvate attenuated the nicotinamide-induced differentiation of the RPE cells. Together, our results demonstrate a remarkable effect of nicotinamide on RPE metabolism. We also identify mitochondrial respiration as a key contributor to the differentiated state of the RPE and thus to many of the RPE functions that are essential for retinal health and photoreception. Competing Interests: Conflict of interest A. S. D. has previously served as a paid consultant for Agilent Technologies. All other authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.) |
| التعليقات: | Erratum in: J Biol Chem. 2022 Sep 30;298(10):102493. (PMID: 36191577) |
| معلومات مُعتمدة: | P30 EY000331 United States EY NEI NIH HHS; P30 DK063491 United States DK NIDDK NIH HHS; R01 EY027442 United States EY NEI NIH HHS; R21 EY031109 United States EY NEI NIH HHS; R35 GM138003 United States GM NIGMS NIH HHS |
| فهرسة مساهمة: | Keywords: RPE; differentiation; mitochondria; nicotinamide; retina |
| المشرفين على المادة: | 25X51I8RD4 (Niacinamide) 8558G7RUTR (Pyruvic Acid) IY9XDZ35W2 (Glucose) |
| تواريخ الأحداث: | Date Created: 20220722 Date Completed: 20220929 Latest Revision: 20221018 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC9396405 |
| DOI: | 10.1016/j.jbc.2022.102286 |
| PMID: | 35868562 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1083-351X |
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| DOI: | 10.1016/j.jbc.2022.102286 |