The Relationship Between Acetylated 8-Oxoguanine DNA Glycosylase 1 And Age-related Cataract

Objective The present study is designed to investigate the relationship between acetylated 8-oxoguanine DNA glycosylase 1(Ac-OGG1) and age-related cataract(ARC), and to clarify the effect of acetyltransferase p300 and deacetylase SIRT1 on the8-oxo-guanine(8-oxo G) excision ability of 8-oxoguanine DNA glycosylase 1(OGG1) in ARC development.Methods A clinical case-control study was conducted in the department of ophthalmology in the Affiliated Hospital of Nantong University. We enrolled 240 ARC patients as ARC group that consisted of three subgroups: age-related cortical cataract,age-related nuclear cataract and age-related posterior subcapsular cataract. Each subgroup contained 80 eyes from 80 patients. The control group included:(1) Age-matched patients with vitreoretinal diseases received transparent lens extraction.(2) Biopsy eyes from donors in our hospital Geneva Gross Eye Bank. Anterior lens capsules were collected by intact continuous curvilinear capsulorhexis. We determined the localization and the proportion of positive lens epithelium cells(LECs) for 8-oxo G, Ac-OGG1, OGG1,p300 and SIRT1 using immunofluorescence. Ac-OGG1 and OGG1 protein levels were analyzed by western blot. The interaction of OGG1 with p300 or SIRT1 in LECs was examined by co-immunoprecipitation.Results ARC group had the higher proportion of 8-oxo G positive LECs than those of control group(P<0.01). In ARC group,the protein levels of Ac-OGG1 were lower, while the levels of OGG1 were higher(P<0.01). The proportion of Ac-OGG1 positive cells was lower, while the proportion of OGG1 positive cells was significantly higher in LECs of ARC group(P<0.01). In LECs,OGG1 can form complexes with p300, and they were colocalized in the nucleus. The proportionof p300-OGG1 positive cells decreased in ARC group(P<0.05). SIRT1 was physically colocalized with OGG1 in the nucleus of LECs, while the proportion of SIRT1-OGG1 positive cells was significantly higher in ARC group(P<0.01).Conclusions(1) Ac-OGG1 can be involved in ARC process by regulating the activity of OGG1.(2) The increase of 8-oxo G may be the result of reduced acetylation level of OGG1 in ARC process.(3)The decrease of Ac-OGG1 may be resulted from insufficient interaction between p300 and OGG1 and/or enhanced interaction between SIRT1 and OGG1.