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Front Physiol. 2015 Feb 3;6:11. doi: 10.3389/fphys.2015.00011. eCollection 2015.

A1M/α1-microglobulin is proteolytically activated by myeloperoxidase, binds its heme group and inhibits low density lipoprotein oxidation.

Author information

1
Division of Infection Medicine, Department of Clinical Sciences, Lund University Lund, Sweden.
2
Division of Immunology, Department of Experimental Medicine, Lund University Lund, Sweden.
3
Division of Nuclear Physics, Department of Physics, Lund University Lund, Sweden.

Abstract

α1-microglobulin (A1M) is a 26 kDa plasma and tissue protein with reductase activity and radical- and heme-binding anti-oxidative functions. In addition, exposure of A1M to hemoglobin has been shown to induce proteolytic elimination of a C-terminal tetrapeptide yielding a heme-degrading form, truncated A1M (t-A1M). Myeloperoxidase (MPO), a heme-containing enzyme that catalyzes the production of free radicals and hypochlorite, is released by neutrophils during the inflammatory response to bacterial infections. MPO-induced low density lipoprotein (LDL)-oxidation in blood has been suggested as a causative factor in atherosclerosis. In this study we have hypothesized that A1M interacts with MPO in a similar mode as with hemoglobin, and is a regulator of its activity. The results show that A1M is proteolytically cleaved, with formation of t-A1M, after exposure to MPO, and that t-A1M contains iron and heme-degradation products. The reaction is dependent of pH, time and concentration of substrates and a pH-value around 7 is shown to be optimal for cleavage. Furthermore, A1M inhibits MPO- and hydrogen peroxide-induced oxidation of LDL. The results suggest that A1M may have a role as an inhibitor of the damaging effects of the neutrophil respiratory burst on bystander tissue components.

KEYWORDS:

C-terminal proteolysis; heme binding; low density lipoprotein; myeloperoxidase; neutrophils; α1-microglobulin

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