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Bharucha, A.E., Kulkarni, A., Choi, K.M., Camilleri, M., Lempke, M., Brunn, G.J., Gibbons, S.J., Zinsmeister, A.R. and Farrugia, G. (2010) First-in-Human Study Demonstrating Pharmacological Activation of Heme Oxygenase-1 in Humans. Clinical Pharmacology & Therapeutics, 87, 187-190.
http://dx.doi.org/10.1038/clpt.2009.221

has been cited by the following article:

• TITLE: Hemin Protects U937 Cells from Oxidative Stress via Glutathione Synthesis

  AUTHORS: Yoshimi Satoh, Kyohei Oyama, Koichi Sakurai

  KEYWORDS: Glutathione, Heme Oxygenase-1, Hemin, Oxidative Stress, Gene Expression

  JOURNAL NAME: Journal of Biophysical Chemistry, Vol.5 No.2, April 23, 2014

  ABSTRACT: Although heme oxygenase-1 and glutathione play important roles in the antioxidant defense system, the sharing and/or cross-talking of the HO-1 and GSH system remain poorly understood. The object of this study is to determine whether the glutathione system is involved in the antioxidant function of hemin. Hydrogen peroxide decreased the viability of the human leukemic monocyte lymphoma cell line U937. When these cells were pretreated with hemin before the addition of hydrogen peroxide, cell death was prevented. An inhibitor of heme oxygenase-1 or glutathione biosynthesis significantly abolished this protective effect of hemin. These results suggest that both heme oxygenase-1 and glutathione are involved in the protective effects of hemin against U937 cell death, which was induced by hydrogen peroxide. Hemin induced an increase in glutathione levels following the upregulation of the gene expression and protein levels of glutamate-cysteine ligase catalytic subunit. The inhibitor of heme oxigenase-1 inhibited the upregulation of glutamate-cysteine ligase catalytic subunit expression. These results suggest that hemin induces glutathione synthesis through heme oxygenase-1 activation to protect cells from hydrogen peroxide-induced oxidative stress.