Identification of JWA as a novel functional gene responsive to environmental oxidative stress induced by benzo[a]pyrene and hydrogen peroxide.

Published

Journal Article

Oxidative stress has been implicated as one of the primary mechanisms inducing DNA damage and believed to mediate aging and progression of numerous age-related diseases, including cancer. JWA, a gene previously described to mediate differentiation of leukemic cells, is also involved in cellular responses to environmental exposures linked to heat shock and chemical-mediated oxidative stresses. However, the precise pathways and mechanisms underlying these phenomena remain to be resolved. Our studies demonstrated that H(2)O(2) is the primary oxidative product responsible for benzo[a]pyrene (B[a]P)-induced JWA expression, and knockdown of JWA elevates H(2)O(2) (100 microM)- and B[a]P (100 microM)-induced DNA damage. In oxidative stress cell culture models, JWA was upregulated. JWA expression regulated a parallel rise in the base excision repair protein XRCC1 but a reduction in PARP1 in response to H(2)O(2)-induced DNA damage. Furthermore, we found that both H(2)O(2) and B[a]P exposure activated nuclear transcription factor I (NFI) in NIH-3T3 cells, which specifically bound to the CCAAT element in the JWA proximal promoter (-58/-28 bp) and thereby induced JWA expression. Consistently siRNA mediated a knockdown of NFI, which prevented JWA induction. These findings indicate that JWA may serve as a novel environmental stress sensor to protect cells against reactive oxygen species-associated DNA damage.

Full Text

Duke Authors

Cited Authors

  • Chen, R; Qiu, W; Liu, Z; Cao, X; Zhu, T; Li, A; Wei, Q; Zhou, J

Published Date

  • June 1, 2007

Published In

Volume / Issue

  • 42 / 11

Start / End Page

  • 1704 - 1714

PubMed ID

  • 17462538

Pubmed Central ID

  • 17462538

International Standard Serial Number (ISSN)

  • 0891-5849

Digital Object Identifier (DOI)

  • 10.1016/j.freeradbiomed.2007.02.018

Language

  • eng

Conference Location

  • United States