title: PRMT1 and PRMT4 Regulate Oxidative Stress-Induced Retinal Pigment Epithelial Cell Damage in SIRT1-Dependent and SIRT1-Independent Manners.
abstract: Oxidative stress-induced retinal pigment epithelial (RPE) cell damage is involved in the progression of diabetic retinopathy. Arginine methylation catalyzed by protein arginine methyltransferases (PRMTs) has emerged as an important histone modification involved in diverse diseases. Sirtuin (SIRT1) is a protein deacetylase implicated in the onset of metabolic diseases. Therefore, we examined the roles of type I PRMTs and their relationship with SIRT1 in human RPE cells under H2O2-induced oxidative stress. H2O2 treatment increased PRMT1 and PRMT4 expression but decreased SIRT1 expression. Similar to H2O2 treatment, PRMT1 or PRMT4 overexpression increased RPE cell damage. Moreover, the H2O2-induced RPE cell damage was attenuated by PRMT1 or PRMT4 knockdown and SIRT1 overexpression. In this study, we revealed that SIRT1 expression was regulated by PRMT1 but not by PRMT4. Finally, we found that PRMT1 and PRMT4 expression is increased in the RPE layer of streptozotocin-treated rats. Taken together, we demonstrated that oxidative stress induces apoptosis both via PRMT1 in a SIRT1-dependent manner and via PRMT4 in a SIRT1-independent manner. The inhibition of the expression of type I PRMTs, especially PRMT1 and PRMT4, and increased SIRT1 could be therapeutic approaches for diabetic retinopathy.
authors.affiliation: College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea ; Life Science Institute, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Dong-Il
authors.initials: DI
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea ; Departments of Molecular & Integrative Physiology and Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Park
authors.affiliation: College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors.forename: Joo-Hee
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Division of Applied Bioscience and Biotechnology, Institute of Environmentally-Friendly Agriculture, College of Agriculture and Life Sciences, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors.forename: In-Seon
authors.initials: IS
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine and Research Institute for Veterinary Science and BK21 PLUS Creative Veterinary Research Center, Seoul National University, Seoul 151-741, Republic of Korea.
authors.forename: Ho-Jae
authors.initials: HJ
authors.lastname: Han
authors.affiliation: Department of Ophthalmology, Chonnam National University Medical School and Hospital, Gwangju 501-757, Republic of Korea.
authors.forename: Kyung-Chul
authors.initials: KC
authors.lastname: Yoon
authors.affiliation: Department of Ophthalmology, Chonnam National University Medical School and Hospital, Gwangju 501-757, Republic of Korea.
authors.forename: Sang-Woo
authors.initials: SW
authors.lastname: Park
authors.affiliation: Department of Molecular Physiology, College of Pharmacy, Kyungpook National University, Taegu 702-701, Republic of Korea.
authors.forename: Min-Young
authors.initials: MY
authors.lastname: Lee
authors.affiliation: College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors.forename: Ki-Seok
authors.initials: KS
authors.lastname: Oh
authors.affiliation: College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors.forename: Soo-Hyun
authors.initials: SH
authors.lastname: Park
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D007150:Immunohistochemistry; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D011484:Protein-Arginine N-Methyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012168:Retinal Pigments / Q000378:metabolism; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D013311:Streptozocin / Q000633:toxicity
chemical_list: D034741:RNA, Small Interfering; D012168:Retinal Pigments; D013311:Streptozocin; D006861:Hydrogen Peroxide; C541817:PRMT1 protein, rat; D011484:Protein-Arginine N-Methyltransferases; C119966:coactivator-associated arginine methyltransferase 1; C488368:Sirt1 protein, rat; D056564:Sirtuin 1