Tobacco-smoke-inducible human haem oxygenase-1 gene expression: role of distinct transcription factors and reactive oxygen intermediates

Exposure of eukaryotic cells to a variety of reactive-oxygen-intermediate ( ROI)-mediated sources of cellular injury, including heavy metals and UV rad iation, induces the expression of heat-shock (HS) and stress-related genes among which is a 32-34 kDa protein identified as inducible haem oxygenase-l (HO-1). We previously showed that tobacco smoke (TS), a potent source of o xidants leading to oxidative stress, induces both HS proteins (HSPs) and HO -1 in normal human monocytes. Here we with consensus elements and binding s ites of the promoter region of HO-1[heat-shock factor (HSF), nuclear factor kappaB (NF-kappaB) and activator protein-1 (AP-I)] and the cadmium-respons ive element (CdRE) isolated by Takeda, Ishizawa, Sate, Yoshida and Shibahar a [(1994) J. Biol. Chem. 269, 22858-22867]. We report an inhibition of NF-k appaB activation by TS, no effect on AP- and a strong activation of CdRE-bi nding activity, whereas cadmium chelation from TS only partially prevented HO-1 induction. H2O2 also activated the CdRE-binding activity, and pretreat ment with N-acetyl-L-cysteine, which replenishes the intracellular levels o f GSH, suppressed. in TS-treated cells, both the CdRE-binding activity and the increased HO-1 expression.