Bach1 deficiency and accompanying overexpression of heme oxygenase-1 do not influence aging or tumorigenesis in mice

Oxid Med Cell Longev. 2014:2014:757901. doi: 10.1155/2014/757901. Epub 2014 Jun 23.

Abstract

Oxidative stress contributes to both aging and tumorigenesis. The transcription factor Bach1, a regulator of oxidative stress response, augments oxidative stress by repressing the expression of heme oxygenase-1 (HO-1) gene (Hmox1) and suppresses oxidative stress-induced cellular senescence by restricting the p53 transcriptional activity. Here we investigated the lifelong effects of Bach1 deficiency on mice. Bach1-deficient mice showed longevity similar to wild-type mice. Although HO-1 was upregulated in the cells of Bach1-deficient animals, the levels of ROS in Bach1-deficient HSCs were comparable to those in wild-type cells. Bach1(-/-); p53(-/-) mice succumbed to spontaneous cancers as frequently as p53-deficient mice. Bach1 deficiency significantly altered transcriptome in the liver of the young mice, which surprisingly became similar to that of wild-type mice during the course of aging. The transcriptome adaptation to Bach1 deficiency may reflect how oxidative stress response is tuned upon genetic and environmental perturbations. We concluded that Bach1 deficiency and accompanying overexpression of HO-1 did not influence aging or p53 deficiency-driven tumorigenesis. Our results suggest that it is useful to target Bach1 for acute injury responses without inducing any apparent deteriorative effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Animals
  • Basic-Leucine Zipper Transcription Factors / deficiency*
  • Basic-Leucine Zipper Transcription Factors / metabolism
  • Carcinogenesis / metabolism*
  • Carcinogenesis / pathology*
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Hematopoietic Stem Cells / metabolism
  • Heme Oxygenase-1 / metabolism*
  • Liver / metabolism
  • Liver / pathology
  • Longevity
  • Mice, Inbred C57BL
  • Transcriptome / genetics
  • Tumor Suppressor Protein p53 / deficiency
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Bach1 protein, mouse
  • Basic-Leucine Zipper Transcription Factors
  • Tumor Suppressor Protein p53
  • Heme Oxygenase-1