Myeloperoxidase in kidney disease.
In glomerular and tubulointerstitial disease, polymorphonuclear- and monocyte-derived reactive oxygen species may contribute to oxidative modification of proteins, lipids, and nucleic acids. In part, the processes instigated by reactive oxygen species parallel events that lead to the development of atherosclerosis. Myeloperoxidase (MPO), a heme protein and catalyst for (lipo)protein oxidation is present in these mononuclear cells. The ability of MPO to generate hypochlorous acid/hypochlorite (HOCl/OCl-) from hydrogen peroxide in the presence of chloride ions is a unique and defining activity for this enzyme. The MPO-hydrogen peroxide-chloride system leads to a variety of chlorinated protein and lipid adducts that in turn may cause dysfunction of cells in different compartments of the kidney. The aim of this article is to cover and interpret some experimental and clinical aspects in glomerular and tubulointerstitial diseases in which the MPO-hydrogen peroxide-chloride system has been considered an important pathophysiologic factor in the progression but also the attenuation of experimental renal disease. The colocalization of MPO and HOCl-modified proteins in glomerular peripheral basement membranes and podocytes in human membranous glomerulonephritis, the presence of HOCl-modified proteins in mononuclear cells of the interstitium and in damaged human tubular epithelia, the inflammation induced and exacerbated by MPO antibody complexes in necrotizing glomerulonephritis, and the presence of HOCl-modified epitopes in urine following hyperlipidemia-induced renal damage in rodents suggest that MPO is an important pathogenic factor in glomerular and tubulointerstitial diseases. Specifically, the interaction of MPO with nitric oxide metabolism adds to the complexity of actions of oxidants and may help to explain bimodal partly detrimental partly beneficial effects of the MPO-hydrogen peroxide-chloride system in redox-modulated renal diseases.
Malle
Ernst
E
Karl-Franzens University Graz, Institute of Medical Biochemistry and Molecular Biology, Graz, Austria.
Buch
Thomas
T
Grone
Hermann-Josef
HJ
D000818:Animals; D018450:Disease Progression; D006801:Humans; D006997:Hypochlorous Acid / Q000378:metabolism; D007154:Immune System Diseases / Q000201:enzymology; D007674:Kidney Diseases / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000473:pathology; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000172:deficiency / Q000378:metabolism*; D012079:Renal Circulation; D015427:Reperfusion Injury / Q000201:enzymology
D006997:Hypochlorous Acid; D009195:Peroxidase