TY - JOUR
T1 - Up-regulation of NDRG2 in senescent lens epithelial cells contributes to age-related cataract in human
AU - Zhang, Zi Feng
AU - Zhang, Jian
AU - Hui, Yan Nian
AU - Zheng, Min Hua
AU - Liu, Xin Ping
AU - Kador, Peter F.
AU - Wang, Yu Sheng
AU - Yao, Li Bo
AU - Zhou, Jian
PY - 2011/10/17
Y1 - 2011/10/17
N2 - 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. Methodology/Principal Findings: Cultured HLECs (SRA01/04) were subjected to prolonged exposure to low dose of H 2O 2 to simulate senescence. After being exposed to 50 μM H 2O 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 2O 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/Significance: 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.
AB - 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. Methodology/Principal Findings: Cultured HLECs (SRA01/04) were subjected to prolonged exposure to low dose of H 2O 2 to simulate senescence. After being exposed to 50 μM H 2O 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 2O 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/Significance: 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.
UR - http://www.scopus.com/inward/record.url?scp=80054768656&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80054768656&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0026102
DO - 10.1371/journal.pone.0026102
M3 - Article
C2 - 22043305
AN - SCOPUS:80054768656
SN - 1932-6203
VL - 6
JO - PloS one
JF - PloS one
IS - 10
M1 - e26102
ER -