Up-regulation of NDRG2 in senescent lens epithelial cells contributes to age-related cataract in human

Zi Feng Zhang, Jian Zhang, Yan Nian Hui, Min Hua Zheng, Xin Ping Liu, Peter F Kador, Yu Sheng Wang, Li Bo Yao, Jian Zhou

Research output: Contribution to journalArticle

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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. 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.

Original languageEnglish (US)
Article numbere26102
JournalPloS one
Volume6
Issue number10
DOIs
Publication statusPublished - Oct 17 2011

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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