Abstract
BackgroundHuman 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.Methodology/Principal FindingsCultured HLECs (SRA01/04) were subjected to prolonged exposure to low dose of H2O2 to simulate senescence. After being exposed to 50 µM H2O2 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 H2O2 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/SignificanceNDRG2 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.
Highlights
N-Myc downstream-regulated gene 2 (NDRG2) [1,2,3] is one of the four members of the N-Myc downstream-regulated gene (NDRG) family, a new class of Myc-repressed genes composed of NDRG1–4 [1,4,5,6,7,8,9,10]
In the present study, using prolonged exposure of human lens epithelial cells (HLECs) to low doses of H2O2 as a model of lens ageing, here we investigated the up-regulation of Ndrg2 protein in these cells
H2O2 in vitro In order to determine whether N-Myc downstream regulated gene2 (NDRG2) is involved in the cellular senescence, we exposed cultured HLECs (SRA01/04) to prolonged low dose of H2O2 to simulate oxidative stress associate with ageing
Summary
N-Myc downstream-regulated gene 2 (NDRG2) [1,2,3] is one of the four members of the N-Myc downstream-regulated gene (NDRG) family, a new class of Myc-repressed genes composed of NDRG1–4 [1,4,5,6,7,8,9,10]. Significant attention has been paid to this gene family due to its potential role as a tumor suppressor as well as its involvement in other diseases. Accumulating data suggests that NDRG2 regulates cellular differentiation and development in vitro and in vivo [21,22,23,24,25], and is involved in cellular response to stress [19,26]. Human N-Myc downstream regulated gene (NDRG2), a novel gene has been cloned and shown to be related to a number of cellular processes, including proliferation, differentiation, stress, and apoptosis. 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
