title: Acetylated 8-oxoguanine DNA glycosylase 1 and its relationship with p300 and SIRT1 in lens epithelium cells from age-related cataract.
abstract: The human 8-oxoguanine-DNA glycosylase 1 (OGG1) is the major DNA glycosylase responsible for repair of 7,8-dihydro-8-oxoguanine (8-oxoG) and ring-opened fapyguanine, critical mutagenic DNA lesions that are induced by reactive oxygen species. OGG1 acetylation has been demonstrated playing an important role in response to DNA damage. Here, we investigated the relationship between acetylated OGG1 (Ac-OGG1) and ARC, and clarified the effect of p300 and SIRT1 on the 8-oxoG excision ability of OGG1 in ARC development. Our results showed that anterior lens capsules from ARC group had higher proportion of 8-oxoG positive LECs than those from control group. OGG1 mRNA and protein levels significantly increased in ARC group compared with control group, while the protein levels of Ac-OGG1 were lower in ARC group. We investigated the factors involved in OGG1 acetylation and found that p300 and SIRT1 are the major acetyltransferases for OGG1 acetylation. We also identified acetylation of K338/K341 lysine residues in OGG1 has an important role on the repair activity of OGG1 to oxidative damage after H2O2 exposure in human lens epithelial cells (HLE-B3). Taken together, these data demonstrate that OGG1 acetylation regulates its function in response to DNA damage and could be one of the mechanisms of ARC.
authors: Eye Institute, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China.
authors: Lihua
authors: L
authors: Kang
authors: Eye Institute, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China; Department of Ophthalmology, First People's Hospital of Changshu City, Affiliated Hospital of Soochow University, Changshu, Jiangsu Province, China.
authors: Weijie
authors: W
authors: Zhao
authors: Eye Institute, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China.
authors: Guowei
authors: G
authors: Zhang
authors: Eye Institute, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China.
authors: Jian
authors: J
authors: Wu
authors: Eye Institute, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China. Electronic address: gtnantongeye@gmail.com.
authors: Huaijin
authors: H
authors: Guan
mesh_terms: D000704:Analysis of Variance; D053148:Caspase 3 / Q000378:metabolism; D002386:Cataract / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004249:DNA Damage / Q000502:physiology; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair / Q000502:physiology; D050881:E1A-Associated p300 Protein / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D006801:Humans; D007903:Lens Capsule, Crystalline / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology; D056564:Sirtuin 1 / Q000378:metabolism*
chemical_list: D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; D053148:Caspase 3; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: 8-Oxoguanine DNA glycosylase1 (OGG1); Acetylation; Age-related cataract (ARC); Oxidative damage; SIRT1; p300