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Cigarette Smoke Induces Cellular Senescence Via P53-Mediated Werner's Syndrome Protein
Abstract   Peer reviewed

Cigarette Smoke Induces Cellular Senescence Via P53-Mediated Werner's Syndrome Protein

Toru Nyunoya, Jun-Ho Jang, Aloysius Klingelhutz, Martin Whitman and Salam Huneidi
American journal of respiratory and critical care medicine, Vol.183(Supplement_1), pp.A2126-A2126
05/01/2011
DOI: 10.1164/ajrccm-conference.2011.183.1_MeetingAbstracts.A2126

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Abstract

Rationale: Werner’s syndrome is a genetic disorder that causes premature aging due to loss-of-function mutations in the Wrn gene encoding a member of the RecQ helicase family. Both WRN protein defects and cigarette smoke accelerate cellular senescence. We recently found that cigarette smoke induces cellular senescence via WRN protein downregulation in cultured lung fibroblasts. Based on these findings, we hypothesized that cigarette smoke induced WRN protein downregulation by activating the senescence-inducing proteins, p53 and p16. Methods: We generated p53- and p16-deficient lung fibroblasts by a retroviral vector encoding shRNA to knockdown each protein. p53-and p16-deficient lung fibroblasts were cultured in the presence or absence of cigarette smoke extract (CSE). Cellular senescence and WRN protein expression were determined. Results: p53 deficient cells were significantly more resistant to CSE-induced WRN protein downregulation and cellular senescence compared with normal lung fibroblasts. In contrast, p16 knockdown prevented neither WRN protein downregulation nor cellular senescence by CSE. Conclusions: Cigarette smoke induces WRN protein downregulation and cellular senescence via the p53 dependent pathway.

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