title: Bach1 deficiency and accompanying overexpression of heme oxygenase-1 do not influence aging or tumorigenesis in mice.
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.
authors: Department of Biochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Sendai 980-0872, Japan ; Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Sendai 980-0872, Japan.
authors: Kazushige
authors: K
authors: Ota
authors: Department of Biochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Sendai 980-0872, Japan.
authors: Andrey
authors: 0000-0002-6180-995X
authors: A
authors: Brydun
authors: Department of Biochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Sendai 980-0872, Japan.
authors: Ari
authors: A
authors: Itoh-Nakadai
authors: Department of Cellular Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8551, Japan.
authors: Jiying
authors: J
authors: Sun
authors: Department of Biochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Sendai 980-0872, Japan ; Center for Regulatory Epigenome and Diseases, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Sendai 980-0872, Japan.
authors: Kazuhiko
authors: 0000-0002-2470-2475
authors: K
authors: Igarashi
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000172:deficiency* / Q000378:metabolism; D063646:Carcinogenesis / Q000378:metabolism* / Q000473:pathology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008136:Longevity; D008810:Mice, Inbred C57BL; D059467:Transcriptome / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000378:metabolism
chemical_list: C486316:Bach1 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors; D016159:Tumor Suppressor Protein p53; D051547:Heme Oxygenase-1