NRF2 and HSF1 coordinately regulate heme oxygenase-1 expression

Sachiye Inouye; Yuta Hatori; Takanori Kubo; Shizuka Saito; Hiroshi Kitamura; Reiko Akagi

doi:10.1016/j.bbrc.2018.10.030

NRF2 and HSF1 coordinately regulate heme oxygenase-1 expression

Biochem Biophys Res Commun. 2018 Nov 17;506(1):7-11. doi: 10.1016/j.bbrc.2018.10.030. Epub 2018 Oct 11.

Authors

Sachiye Inouye¹, Yuta Hatori², Takanori Kubo², Shizuka Saito², Hiroshi Kitamura³, Reiko Akagi²

Affiliations

¹ Department of Pharmacy, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Japan. Electronic address: inoues@rs.socu.ac.jp.
² Department of Pharmacy, Yasuda Women's University, Japan.
³ Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University, Japan.

PMID: 30316516
DOI: 10.1016/j.bbrc.2018.10.030

Abstract

Heme oxygenase-1 (HO-1) is an inducible enzyme responding to various stresses and has cytoprotective activities. Although HO-1 has been referred to as heat shock protein (HSP) 32, the heat-mediated induction of HO-1 varies among different species and cell lines. We examined the effects of heat shock on HO-1 expression in mouse embryonic fibroblast (MEF) cells deficient in heat shock factor 1 (HSF1) or nuclear factor-erythroid-2-related factor 2 (NRF2). Heme-induced expression of HO-1 was 2-fold higher in Hsf1^-/- cells than in the wild-type cells at both mRNA and protein levels. In Nrf2^-/- cells, heme-induced expression of HO-1 was not detected. In contrast, HO-1 expression was markedly induced by heat shock at 40-42 °C in Nrf2^-/- cells while the wild-type cells were not responsive. The heat-induced expression of HO-1 in Nrf2^-/- cells were almost completely diminished by transfection of siRNA against Hsf1 gene. These results suggest that HSF1 and NRF2 suppress heme-induced and heat-induced HO-1 expression, respectively.

Keywords: Heat shock factor 1 (HSF1); Heme oxygenase-1 (HO-1); Nuclear factor-erythroid-2-related factor 2 (NRF2); Stress response.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line, Transformed
Embryo, Mammalian
Fibroblasts / cytology
Fibroblasts / metabolism*
Gene Expression Regulation
Heat Shock Transcription Factors / antagonists & inhibitors
Heat Shock Transcription Factors / deficiency
Heat Shock Transcription Factors / genetics*
Heat-Shock Response / genetics*
Heme Oxygenase-1 / genetics*
Heme Oxygenase-1 / metabolism
Membrane Proteins / genetics*
Membrane Proteins / metabolism
Mice
NF-E2-Related Factor 2 / deficiency
NF-E2-Related Factor 2 / genetics*
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Signal Transduction

Substances

HSF1 protein, human
Heat Shock Transcription Factors
Membrane Proteins
NF-E2-Related Factor 2
Nfe2l2 protein, mouse
RNA, Small Interfering
Heme Oxygenase-1
Hmox1 protein, mouse