Heme Oxygenase-2/adiponectin Protein-protein Interaction in Metabolic Syndrome

Overview

Journal Biochem Biophys Res Commun

Publisher Elsevier

Specialty Biochemistry

Date 2013 Feb 27

PMID 23438433

Citations 9

Authors

Luca Vanella

Giovanni Li Volti

Salvatore Guccione

Giancarlo Rappazzo

Eliana Salvo

Morena Pappalardo

Stefano Forte

Michal L Schwartzman

Nader G Abraham

Affiliations

Soon will be listed here.

Abstract

Insulin resistance with adipose tissue dysfunction and dysregulation in the production and secretion of adipokines is one of the hallmarks of metabolic syndrome. We have previously reported that increased levels of the heme oxygenase (HO) system, HO-1/HO-2 results in increased levels of adiponectin. Despite documentation of the existence of the anti-inflammatory axis HO-adiponectin, a possible protein-protein interaction between HO and adiponectin has not been examined. Here, we investigated the existence of protein interactions between HO-2 and adiponectin in the maintenance of adipocyte function during metabolic syndrome by integrating phenotypic and in silico studies. Compared to WT animals, HO-2 null mice displayed an increase in both visceral and subcutaneous fat content and reduced circulating adiponectin levels. The decrease in adiponectin was reversed by upregulation of HO-1. HO-2 depletion was associated with increased adipogenesis in cultured mesenchymal stem cells (MSCs) and decreased adiponectin levels in the culture media. In addition, HO-1 siRNA decreased adiponectin release. HO-2 was found to bind to the monomeric form of adiponectin, according to poses and calculated energies. HO-2-adiponectin interactions were validated by the two-hybrid system assay. In conclusion, protein-protein interactions between HO-2 and adiponectin highlight the role of HO-2 as a molecular chaperone for adiponectin assembly, while HO-1 increases adiponectin levels. Thus, crosstalk between HO-2 and HO-1 could be manipulated in a therapeutic approach to ameliorate the deleterious effects of obesity and the metabolic syndrome.

Citing Articles

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References

Okamoto Y, Kihara S, Ouchi N, Nishida M, Arita Y, Kumada M . Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation. 2002; 106(22):2767-70. DOI: 10.1161/01.cir.0000042707.50032.19. View

Sambuceti G, Morbelli S, Vanella L, Kusmic C, Marini C, Massollo M . Diabetes impairs the vascular recruitment of normal stem cells by oxidant damage, reversed by increases in pAMPK, heme oxygenase-1, and adiponectin. Stem Cells. 2008; 27(2):399-407. PMC: 2729677. DOI: 10.1634/stemcells.2008-0800. View

Abraham N, Kappas A . Heme oxygenase and the cardiovascular-renal system. Free Radic Biol Med. 2005; 39(1):1-25. DOI: 10.1016/j.freeradbiomed.2005.03.010. View

Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S . Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med. 2002; 8(11):1288-95. DOI: 10.1038/nm788. View

Lin Q, Weis S, Yang G, Weng Y, Helston R, Rish K . Heme oxygenase-1 protein localizes to the nucleus and activates transcription factors important in oxidative stress. J Biol Chem. 2007; 282(28):20621-33. DOI: 10.1074/jbc.M607954200. View

Serebriiskii I, Milech N, Golemis E . A bacterial/yeast merged two-hybrid system: protocol for bacterial screening. Methods Mol Biol. 2008; 408:291-315. DOI: 10.1007/978-1-59745-547-3_16. View

Ohashi K, Kihara S, Ouchi N, Kumada M, Fujita K, Hiuge A . Adiponectin replenishment ameliorates obesity-related hypertension. Hypertension. 2006; 47(6):1108-16. DOI: 10.1161/01.HYP.0000222368.43759.a1. View

Burgess A, Vanella L, Bellner L, Gotlinger K, Falck J, Abraham N . Heme oxygenase (HO-1) rescue of adipocyte dysfunction in HO-2 deficient mice via recruitment of epoxyeicosatrienoic acids (EETs) and adiponectin. Cell Physiol Biochem. 2012; 29(1-2):99-110. PMC: 3711769. DOI: 10.1159/000337591. View

Bluher M . Adipose tissue dysfunction in obesity. Exp Clin Endocrinol Diabetes. 2009; 117(6):241-50. DOI: 10.1055/s-0029-1192044. View

10.

Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J . Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 1999; 257(1):79-83. DOI: 10.1006/bbrc.1999.0255. View

11.

Wang Z, Schraw T, Kim J, Khan T, Rajala M, Follenzi A . Secretion of the adipocyte-specific secretory protein adiponectin critically depends on thiol-mediated protein retention. Mol Cell Biol. 2007; 27(10):3716-31. PMC: 1899995. DOI: 10.1128/MCB.00931-06. View

12.

Volti G, Ientile R, Abraham N, Vanella A, Cannavo G, Mazza F . Immunocytochemical localization and expression of heme oxygenase-1 in primary astroglial cell cultures during differentiation: effect of glutamate. Biochem Biophys Res Commun. 2004; 315(2):517-24. DOI: 10.1016/j.bbrc.2004.01.090. View

13.

Abraham N, Li M, Vanella L, Peterson S, Ikehara S, Asprinio D . Bone marrow stem cell transplant into intra-bone cavity prevents type 2 diabetes: role of heme oxygenase-adiponectin. J Autoimmun. 2008; 30(3):128-35. DOI: 10.1016/j.jaut.2007.12.005. View

14.

Cinti S . The adipose organ. Prostaglandins Leukot Essent Fatty Acids. 2005; 73(1):9-15. DOI: 10.1016/j.plefa.2005.04.010. View

15.

Nicolai A, Li M, Kim D, Peterson S, Vanella L, Positano V . Heme oxygenase-1 induction remodels adipose tissue and improves insulin sensitivity in obesity-induced diabetic rats. Hypertension. 2009; 53(3):508-15. PMC: 2745551. DOI: 10.1161/HYPERTENSIONAHA.108.124701. View

16.

Rahal O, Simmen R . Paracrine-acting adiponectin promotes mammary epithelial differentiation and synergizes with genistein to enhance transcriptional response to estrogen receptor β signaling. Endocrinology. 2011; 152(9):3409-21. DOI: 10.1210/en.2011-1085. View

17.

Vanella L, Kim D, Sodhi K, Barbagallo I, Burgess A, Falck J . Crosstalk between EET and HO-1 downregulates Bach1 and adipogenic marker expression in mesenchymal stem cell derived adipocytes. Prostaglandins Other Lipid Mediat. 2011; 96(1-4):54-62. PMC: 3645487. DOI: 10.1016/j.prostaglandins.2011.07.005. View

18.

Poss K, Thomas M, Ebralidze A, ODell T, Tonegawa S . Hippocampal long-term potentiation is normal in heme oxygenase-2 mutant mice. Neuron. 1995; 15(4):867-73. DOI: 10.1016/0896-6273(95)90177-9. View

19.

Abraham N, Kappas A . Pharmacological and clinical aspects of heme oxygenase. Pharmacol Rev. 2008; 60(1):79-127. DOI: 10.1124/pr.107.07104. View

20.

Li M, Kim D, Tsenovoy P, Peterson S, Rezzani R, Rodella L . Treatment of obese diabetic mice with a heme oxygenase inducer reduces visceral and subcutaneous adiposity, increases adiponectin levels, and improves insulin sensitivity and glucose tolerance. Diabetes. 2008; 57(6):1526-35. DOI: 10.2337/db07-1764. View