Cytoglobin expression in oxidative stressed liver during systemic chronic normobaric hypoxia and relation with HIF-1α
Background: Liver is sensitive against hypoxia and hypoxia will stabilize HIF-1α. At the same time, hypoxia will produce reactive oxygen species (ROS) which can be scavenged by Cygb. The purpose of our study is to know, if normobaric hypoxia can induce Cygb expression and its association with HIF-1α stabilization.
Methods: This is an experimental study using 28 male Sprague-Dawley rats, 150-200 g weight. Rats are divided into 7 groups: control group and treatment groups that are kept in hypoxic chamber (10% O2: 90% N2) for 6 hours, 1, 2, 3, 7 and 14 days. All rats are euthanized after treatment and liver tissue are isolated, homogenized and analyzed for oxidative stress parameter, expression of Cygb and HIF-1α.
Results: Expression of Cygb mRNA and protein was increased on the day-1 after treatment and reach the maximum expression on the day-2 of hypoxia treatment. But, the expression was decreased after the day-3 and slightly increased at the day-14 of hypoxia. The correlation between expression of Cygb and oxidative stress parameter was strongly correlated. Cygb mRNA, as well as protein, showed the same kinetic as the HIF-1, all increased about day-1 and day-2.Conclusion: Systemic chronic hypoxia and/or oxidative stress up-regulated HIF-1α mRNA which is correlated with the Cygb mRNA and protein expression. Cygb mRNA as well as Cygb protein showed the same kinetic as the HIF-1, all increased about day-1 and day-2 suggesting that Cygb could be under the regulation of HIF-1, but could be controlled also by other factor than HIF-1.
Pesce A, Bolognesi M, Bocedi A, Ascenzi P, Dewilde S, Moens L et al. Neuroglobin and cytoglobin. Fresh blood for the vertebrate globin family. EMBO Rept. 2002;3(12):1146-51. http://dx.doi.org/10.1093/embo-reports/kvf248
Hamdane D, Kiger L, Dewilde S, Green BN, Pesce A, Uzan J, et al. The redox state of the cell regulates the ligand binding affinity of human neuroglobin and cytoglobin. J Biol Chem. 2003;278(51):51713-21. http://dx.doi.org/10.1074/jbc.M309396200
Ebner B, Panopolou G, Vinogradov SN, Kiger L, Marden MC, Burmester T, et al. The globin gene family of the cephalochordate amphioxus: implications for chordate globin evolution. BMC Evol Biol. 2010;10:370. http://dx.doi.org/10.1186/1471-2148-10-370
Blank M, Wollberg J, Gerlach F, Reimann K, Roesner A, Hankeln T, et al. A membrane-bound vertebrate globin. PLoS ONE. 2011;6(9):e25292. http://dx.doi.org/10.1371/journal.pone.0025292
Schmidt M, Gerlach F, Avivi A, Laufs T, Wystub S, Simpson JC, et al. Cytoglobin is a respiratory protein in connective tissue and neurons, which is up-regulated by hypoxia. J Biol Chem. 2004;279(9):8063-9. http://dx.doi.org/10.1074/jbc.M310540200
Hankeln T, Ebner B, Fuchs C, Gerlach F, Haberkamp M, Laufs TL et al. Neuroglobin and cytoglobin in search of their role in the vertebrate globin family. J Inorg Biochem. 2005;99(1):110-9. http://dx.doi.org/10.1016/j.jinorgbio.2004.11.009
Fordel E, Thijs L, Moens L, Dewilde S. Neuroglobin and cytoglobin expression in mice. Evidence for a correlation with with reactive species scavenging. FEBS J. 2007;274(5):1312-7. http://dx.doi.org/10.1111/j.1742-4658.2007.05679.x
Xu R, Harrison PM, Chen M, Li L, Tsui L, Fung PCW, et al. Cytoglobin overexpression protects against damage-induced fibrosis. Mol Ther. 2006;13(6):1093-9. http://dx.doi.org/10.1016/j.ymthe.2005.11.027
Jusman SW, Halim A, Wanandi SI, Sadikin M. Expression of hypoxia-inducible factor-1α (HIF-1α) related to oxidative stress in liver of rat-induced by systemic chronic normobaric hypoxia. Acta med Indones. 2010;42(1):17-23.
Bonello S, Zahringer C, BelAiba RS, Djordjevic T, Hess J, Michiels C, et al. Reactive oxygen species activate the HIF-1α promoter via a functional NFκB site. Arterioscler Thromb Vasc Biol. 2007;27(4):755-61. http://dx.doi.org/10.1161/01.ATV.0000258979.92828.bc
Ferdinal F, Suyatna FD, Wanandi SI, Sadikin M. Expression of B-type natriuretic peptide-45 (BNP-45) gene in the ventricular myocardial induced by systemic chronic hypoxia. Acta Med Indones. 2009;41(3):136-43.
Syam AF, Simadibrata M, Wanandi SI, Hernowo BS, Sadikin M, Rani AA. Gastric ulcers induced by systemic hypoxia. Acta Med Indones. 2011;43(4):243-8.
Hoogewijs D, Geuens E, Dewilde S, Vierstraete A, Moens L, Vinogradov S, et al. Wide diversity in structure and expression profiles among members of Caenorhabditis elegans globin protein family. BMC Genomics. 2007;8:356. http://dx.doi.org/10.1186/1471-2164-8-356
Fordel E, Geuens E, Dewilde S, Rottiers P, Carmeliet P, Grooten J, et al. Cytoglobin expression is upregulated in all tissues upon hypoxia: An in vitro and in vivo study by quantitative real-time PCR. Biochem Biophys Res Commun. 2004;319(2):342-8. http://dx.doi.org/10.1016/j.bbrc.2004.05.010
Singh S, Manda SM, Sikder D, Birrer MJ, Rothermel BA, Garry J, et al. Calcineurin activates cytoglobin transcription in hypoxic myocytes. J Biol Chem. 2009;284(16):10409-21. http://dx.doi.org/10.1074/jbc.M809572200
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