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Protective Effect of Melatonin against Oxidative Stress-Induced Apoptosis and Enhanced Autophagy in Human Retinal Pigment Epithelium Cells.
Oxid Med Cell Longev 2018; 2018:9015765OM

Abstract

Age-related macular degeneration (AMD) affects the retinal macula and results in loss of vision, and AMD is the primary cause of blindness and severe visual impairment among elderly people worldwide. AMD is characterized by the accumulation of drusen in the Bruch's membrane and dysfunction of retinal pigment epithelial (RPE) cells and photoreceptors. The pathogenesis of AMD remains unclear, and no effective treatment exists. Accumulating evidence indicates that oxidative stress plays a critical role in RPE cell degeneration and AMD. Melatonin is an antioxidant that scavenges free radicals, and it has anti-inflammatory, antitumor, and antiangiogenic effects. This study investigated the antioxidative, antiapoptotic, and autophagic effects of melatonin on oxidative damage to RPE cells. We used hydrogen peroxide (H2O2) to stimulate reactive oxygen species production to cause cell apoptosis in ARPE-19 cell lines. Our findings revealed that treatment with melatonin significantly inhibited H2O2-induced RPE cell damage, decreased the apoptotic rate, increased the mitochondrial membrane potential, and increased the autophagy effect. Furthermore, melatonin reduced the Bax/Bcl-2 ratio and the expression levels of the apoptosis-associated proteins cytochrome c and caspase 7. Additionally, melatonin upregulated the expression of the autophagy-related proteins LC3-II and Beclin-1 and downregulated the expression of p62. Thus, melatonin's effects on autophagy and apoptosis can protect against H2O2-induced oxidative damage in human RPE cells. Melatonin may have multiple protective effects on human RPE cells against H2O2-induced oxidative damage.

Authors+Show Affiliations

School of Nutrition and Health Sciences, Taipei Medical University, Taipei, Taiwan.School of Nutrition and Health Sciences, Taipei Medical University, Taipei, Taiwan.School of Nutrition and Health Sciences, Taipei Medical University, Taipei, Taiwan.PhD Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei, Taiwan.PhD Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei, Taiwan.Department of Ophthalmology, Yangming Branch, Taipei City Hospital, Taipei, Taiwan. Department of Optometry, University of Kang Ning, Taipei, Taiwan. Department of Health and Welfare, College of City Management, University of Taipei, Taipei, Taiwan.School of Nutrition and Health Sciences, Taipei Medical University, Taipei, Taiwan. Graduate Institute of Metabolism and Obesity Sciences, Taipei Medical University, Taipei, Taiwan. School of Food and Safety, Taipei Medical University, Taipei, Taiwan. Nutrition Research Center, Taipei Medical University Hospital, Taipei, Taiwan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30174783

Citation

Chang, Chih-Chao, et al. "Protective Effect of Melatonin Against Oxidative Stress-Induced Apoptosis and Enhanced Autophagy in Human Retinal Pigment Epithelium Cells." Oxidative Medicine and Cellular Longevity, vol. 2018, 2018, p. 9015765.
Chang CC, Huang TY, Chen HY, et al. Protective Effect of Melatonin against Oxidative Stress-Induced Apoptosis and Enhanced Autophagy in Human Retinal Pigment Epithelium Cells. Oxid Med Cell Longev. 2018;2018:9015765.
Chang, C. C., Huang, T. Y., Chen, H. Y., Huang, T. C., Lin, L. C., Chang, Y. J., & Hsia, S. M. (2018). Protective Effect of Melatonin against Oxidative Stress-Induced Apoptosis and Enhanced Autophagy in Human Retinal Pigment Epithelium Cells. Oxidative Medicine and Cellular Longevity, 2018, p. 9015765. doi:10.1155/2018/9015765.
Chang CC, et al. Protective Effect of Melatonin Against Oxidative Stress-Induced Apoptosis and Enhanced Autophagy in Human Retinal Pigment Epithelium Cells. Oxid Med Cell Longev. 2018;2018:9015765. PubMed PMID: 30174783.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective Effect of Melatonin against Oxidative Stress-Induced Apoptosis and Enhanced Autophagy in Human Retinal Pigment Epithelium Cells. AU - Chang,Chih-Chao, AU - Huang,Tien-Yi, AU - Chen,Hsin-Yuan, AU - Huang,Tsui-Chin, AU - Lin,Li-Chun, AU - Chang,Yen-Jui, AU - Hsia,Shih-Min, Y1 - 2018/08/05/ PY - 2018/03/14/received PY - 2018/06/01/revised PY - 2018/06/06/accepted PY - 2018/9/4/entrez PY - 2018/9/4/pubmed PY - 2019/1/3/medline SP - 9015765 EP - 9015765 JF - Oxidative medicine and cellular longevity JO - Oxid Med Cell Longev VL - 2018 N2 - Age-related macular degeneration (AMD) affects the retinal macula and results in loss of vision, and AMD is the primary cause of blindness and severe visual impairment among elderly people worldwide. AMD is characterized by the accumulation of drusen in the Bruch's membrane and dysfunction of retinal pigment epithelial (RPE) cells and photoreceptors. The pathogenesis of AMD remains unclear, and no effective treatment exists. Accumulating evidence indicates that oxidative stress plays a critical role in RPE cell degeneration and AMD. Melatonin is an antioxidant that scavenges free radicals, and it has anti-inflammatory, antitumor, and antiangiogenic effects. This study investigated the antioxidative, antiapoptotic, and autophagic effects of melatonin on oxidative damage to RPE cells. We used hydrogen peroxide (H2O2) to stimulate reactive oxygen species production to cause cell apoptosis in ARPE-19 cell lines. Our findings revealed that treatment with melatonin significantly inhibited H2O2-induced RPE cell damage, decreased the apoptotic rate, increased the mitochondrial membrane potential, and increased the autophagy effect. Furthermore, melatonin reduced the Bax/Bcl-2 ratio and the expression levels of the apoptosis-associated proteins cytochrome c and caspase 7. Additionally, melatonin upregulated the expression of the autophagy-related proteins LC3-II and Beclin-1 and downregulated the expression of p62. Thus, melatonin's effects on autophagy and apoptosis can protect against H2O2-induced oxidative damage in human RPE cells. Melatonin may have multiple protective effects on human RPE cells against H2O2-induced oxidative damage. SN - 1942-0994 UR - https://www.unboundmedicine.com/medline/citation/30174783/Protective_Effect_of_Melatonin_against_Oxidative_Stress_Induced_Apoptosis_and_Enhanced_Autophagy_in_Human_Retinal_Pigment_Epithelium_Cells_ L2 - https://dx.doi.org/10.1155/2018/9015765 DB - PRIME DP - Unbound Medicine ER -