Endocrinol Metab (Seoul). 2014 Sep;29(3):356-62. doi: 10.3803/EnM.2014.29.3.356. Epub 2014 Sep 25.
Protective Effects of Inducible HO-1 on Oxygen Toxicity in Rat Brain Endothelial Microvessel Cells.
Endocrinology and metabolism (Seoul, Korea)
Seung-Jun Yoo, Neal K Nakra, Gabriele V Ronnett, Cheil Moon
Affiliations
Affiliations
- Department of Brain Science, Graduate School, Daegu Gyeungbuk Institute of Science and Technology (DGIST), Daegu, Korea.
- Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
- Department of Brain Science, Graduate School, Daegu Gyeungbuk Institute of Science and Technology (DGIST), Daegu, Korea. ; Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. ; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. ; Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. ; Center for Metabolism and Obesity Research, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
PMID: 25309795
PMCID: PMC4192800 DOI: 10.3803/EnM.2014.29.3.356
Abstract
BACKGROUND: Reperfusion in ischemia is believed to generate cytotoxic oxidative stress, which mediates reperfusion injury. These stress conditions can initiate lipid peroxidation and damage to proteins, as well as promote DNA strand breaks. As biliverdin and bilirubin produced by heme oxygenase isoform 1 (HO-1) have antioxidant properties, the production of both antioxidants by HO-1 may help increase the resistance of the ischemic brain to oxidative stress. In the present study, the survival effect of HO-1 was confirmed using hemin.
METHODS: To confirm the roles of HO-1, carbon monoxide, and cyclic guanosine monophosphate further in the antioxidant effect of HO-1 and bilirubin, cells were treated with cycloheximide, desferoxamine, and zinc deuteroporphyrin IX 2,4 bis glycol, respectively.
RESULTS: HO-1 itself acted as an antioxidant. Furthermore, iron, rather than carbon monoxide, was involved in the HO-1-mediated survival effect. HO-1 activity was also important in providing bilirubin as an antioxidant.
CONCLUSION: Our results suggested that HO-1 helped to increase the resistance of the ischemic brain to oxidative stress.
Keywords: Bilirubin; Carbon monoxide; Heme; Iron; Oxygenases
References
- FASEB J. 1988 Jul;2(10):2557-68 - PubMed
- Science. 1993 Jan 15;259(5093):381-4 - PubMed
- Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5364-8 - PubMed
- Brain Res Mol Brain Res. 1996 Apr;37(1-2):201-8 - PubMed
- Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16093-8 - PubMed
- Atherosclerosis. 1998 Feb;136(2):383-7 - PubMed
- J Biol Chem. 1998 Apr 3;273(14):8360-8 - PubMed
- Am J Physiol Heart Circ Physiol. 2005 Jun;288(6):H2843-50 - PubMed
- Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):10996-1002 - PubMed
- Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):795-8 - PubMed
- Curr Opin Lipidol. 1994 Dec;5(6):422-33 - PubMed
- Physiol Rev. 2004 Oct;84(4):1381-478 - PubMed
- J Cereb Blood Flow Metab. 1993 Jan;13(1):105-15 - PubMed
- Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):688-92 - PubMed
- Antioxid Redox Signal. 2006 Mar-Apr;8(3-4):444-77 - PubMed
- Nitric Oxide. 2005 Mar;12(2):70-9 - PubMed
- J Cell Biol. 1986 Nov;103(5):2035-52 - PubMed
- Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2445-50 - PubMed
- J Biol Chem. 1990 May 15;265(14):8212-7 - PubMed
- Gene. 2004 Jul 21;336(2):241-50 - PubMed
- Am J Respir Cell Mol Biol. 1996 Jul;15(1):9-19 - PubMed
- Glia. 1992;5(4):300-5 - PubMed
- Ann N Y Acad Sci. 1999;890:167-72 - PubMed
- Science. 1987 Feb 27;235(4792):1043-6 - PubMed
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