title: Lowered Nudix type 5 expression leads to cellular senescence in IMR-90 fibroblast cells.
abstract: The molecule 8-oxo-7,8-dihydroguanine (8-oxoGua), an oxidized form of guanine, can pair with adenine or cytosine during nucleic acid synthesis. RNA sequences that contain 8-oxoGua cause translational errors that lead to the synthesis of abnormal proteins. Human Nudix type 5 (NUDT5), a MutT-related protein, catalyzes the hydrolysis of 8-oxoGDP to 8-oxoGMP, thereby preventing the misincorporation of 8-oxoGua into RNA. To investigate the biological roles of NUDT5 in human fibroblast cells, we established cell lines with decreased levels of NUDT5 expression. In NUDT5 knockdown cells, the RNA oxidation levels were significantly higher, the rates of cellular senescence and cell apoptosis were significantly increased, and the cell viability was significantly decreased in comparison with control cells. These results suggested that the NUDT5 protein could play significant roles in the prevention of RNA oxidation and survival in human fibroblast cells.
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, PR China.
authors.forename: L- Q
authors.initials: L
authors.lastname: Zhang
authors.forename: X-N
authors.initials: XN
authors.lastname: Song
authors.forename: D-P
authors.initials: DP
authors.lastname: Dai
authors.forename: X-Y
authors.initials: XY
authors.lastname: Zhou
authors.forename: W
authors.initials: W
authors.lastname: Gan
authors.forename: Y
authors.initials: Y
authors.lastname: Takagi
authors.forename: H
authors.initials: H
authors.lastname: Hayakawa
authors.forename: M
authors.initials: M
authors.lastname: Sekiguchi
authors.forename: J-P
authors.initials: JP
authors.lastname: Cai
mesh_terms: D017209:Apoptosis; D055162:Biocatalysis; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D016922:Cellular Senescence; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D006147:Guanine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D010084:Oxidation-Reduction; D011755:Pyrophosphatases / Q000096:biosynthesis* / Q000378:metabolism; D012313:RNA / Q000737:chemistry / Q000378:metabolism
chemical_list: C024829:8-hydroxyguanine; D006147:Guanine; D012313:RNA; C403715:NUDT5 protein, human; D011755:Pyrophosphatases