title: Up-regulation of NDRG2 in senescent lens epithelial cells contributes to age-related cataract in human.
abstract: BACKGROUND
  Human N-Myc downstream regulated gene2 (NDRG2), a novel gene has been cloned and shown to be related to a number of cellular processes, including proliferation, differentiation, stress, and apoptosis. NDRG2 has also been linked to age-related Alzheimer's disease. Since the role of this gene in senescence is limited, we have investigated the potential role of NDRG2 in human lens epithelial cells (HLECs), a paradigm implicated in age-related cataract.
  
  
  RESULTS
  Cultured HLECs (SRA01/04) were subjected to prolonged exposure to low dose of H(2)O(2) to simulate senescence. After being exposed to 50 µM H(2)O(2) for 2 weeks, HLECs senescent-morphological changes appeared, cell viability decreased dramatically, cell proliferation reduced from 37.4% to 16.1%, and senescence-associated β-galactosidase activity increased from 0 to 90.3%. Ndrg2 protein expression was also significantly increased in these senescent cells. To induce overexpression of NDRG2, SRA01/04 cells were infected with the adenoviral vector of NDRG2. In these cells, overexpression of NDRG2 resulted in a fibroblast-like appearance and the cell viability decreased about 20%. In addition, the NDRG2-overexpression cells demonstrated 20% lower viability when exposed to 50-200 µM H(2)O(2) for acute oxidative stress. Furthermore, the expression of NDRG2 from age-related cataracts was up-regulated 2-fold at both mRNA and protein levels compared with the clear lenses.
  
  
  CONCLUSIONS
  NDRG2 is up regulated not only in the ageing process of HLECs in vitro but also in the cells from human age-related cortical cataract in vivo. Up-regulation of NDRG2 induces cell morphological changes, reduces cell viability, and especially lowers cellular resistance to oxidative stress. NDRG2-mediated affects in HLECs may associate with age-related cataract formation.
authors: Department of Ophthalmology, Eye Institute of Chinese PLA, Xi-Jing Hospital, Fourth Military Medical University, Xi'an, China.
authors: Zi-Feng
authors: ZF
authors: Zhang
authors: Jian
authors: J
authors: Zhang
authors: Yan-Nian
authors: YN
authors: Hui
authors: Min-Hua
authors: MH
authors: Zheng
authors: Xin-Ping
authors: XP
authors: Liu
authors: Peter F
authors: PF
authors: Kador
authors: Yu-Sheng
authors: YS
authors: Wang
authors: Li-Bo
authors: LB
authors: Yao
authors: Jian
authors: J
authors: Zhou
mesh_terms: D002386:Cataract / Q000209:etiology*; D049109:Cell Proliferation; D048430:Cell Shape; D002470:Cell Survival; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007908:Lens, Crystalline / Q000166:cytology*; D018384:Oxidative Stress; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000502:physiology*; D015854:Up-Regulation
chemical_list: C466228:NDRG2 protein, human; D025521:Tumor Suppressor Proteins; D006861:Hydrogen Peroxide