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Hemeoxygenase‐1: a cytoprotective gene with broad therapeutic potential in xenotransplantation and other inflammatory diseases
Author(s) -
Soares M.
Publication year - 2010
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/j.1399-3089.2010.00573_6.x
Subject(s) - cytoprotection , xenotransplantation , hmox1 , transplantation , context (archaeology) , heme oxygenase , biology , oxidative stress , microbiology and biotechnology , immunology , heme , medicine , biochemistry , enzyme , paleontology
Cells have a variety of constitutive and inducible defense cytoprotective mechanisms against oxidative stress. These aim at re‐establishing homeostasis in response to oxidative injury. In the particular context of organ (xeno)transplantation, these defense mechanisms contribute in a critical manner to sustain (xeno)graft survival via at least two interrelated mechanisms. First, cytoprotection per se supports survival and function of cells within a (xeno)transplanted organ and as such should have a beneficial effect in terms of sustaining (xeno)graft survival. Second, cytoprotection reduces immunogenicity of the (xeno)transplanted organ and thus should modulate the activation of the recipient's immune response in a manner that sustains (xeno)graft survival. Others and we have gathered evidence, to suggest that the stress‐responsive enzyme hemeoxygenase‐1 (HO‐1 encoded by the gene Hmox1) acts in such a manner. Upon (xeno)transplantation, HO‐1 becomes ubiquitously expressed in the transplanted organ, acting as the rate‐limiting enzyme in the catabolism of free heme into carbon monoxide (CO), iron (Fe) and biliverdin. There is now accumulating evidence to support the notion that HO‐1 expression in a (xeno)graft and/or in the recipient can have salutary effects that prevent the rejection of that (xeno)graft. In this talk I will argue and provide experimental evidence that this salutary effect might be mediated by the ability of HO‐1 to limit the deleterious effects of free heme. The possibility of using this “protective effect” to support the survival of transplanted organs will be addressed in the particular context of xenotransplantation.