Biochemical and Biophysical Research Communications, Vol.506, No.1, 7-11, 2018
NRF2 and HSF1 coordinately regulate heme oxygenase-1 expression
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 degrees 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. (C) 2018 Elsevier Inc. All rights reserved.
Keywords:Herne oxygenase-1 (HO-1);Heat shock factor 1 (HSF1);Nuclear factor-erythroid-2-related factor 2 (NRF2);Stress response