NRF2 and HSF1 coordinately regulate heme oxygenase-1 expression

• Published in: Biochemical and biophysical research communications 2018-11, Vol.506 (1), p.7-11
• Main Authors: Inouye, Sachiye, Hatori, Yuta, Kubo, Takanori, Saito, Shizuka, Kitamura, Hiroshi, Akagi, Reiko
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Animals; Cell Line, Transformed; Embryo, Mammalian; FIBROBLASTS; Fibroblasts - cytology; Fibroblasts - metabolism; Gene Expression Regulation; Heat shock factor 1 (HSF1); Heat Shock Transcription Factors - antagonists & inhibitors; Heat Shock Transcription Factors - deficiency; Heat Shock Transcription Factors - genetics; HEAT-SHOCK PROTEINS; Heat-Shock Response - genetics; HEME; Heme oxygenase-1 (HO-1); Heme Oxygenase-1 - genetics; Heme Oxygenase-1 - metabolism; Membrane Proteins - genetics; Membrane Proteins - metabolism; MESSENGER-RNA; MICE; NF-E2-Related Factor 2 - deficiency; NF-E2-Related Factor 2 - genetics; Nuclear factor-erythroid-2-related factor 2 (NRF2); OXYGENASES; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Signal Transduction; Stress response
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2018.10.030

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.