Pyridoxamine protects proteins from damage by hypohalous acids in vitro and in vivo.

Madu H, Avance J, Chetyrkin S, Darris C, Rose KL, Sanchez OA, Hudson B, Voziyan P
Free Radic Biol Med. 2015 89: 83-90

PMID: 26159508 · PMCID: PMC4684779 · DOI:10.1016/j.freeradbiomed.2015.07.001

Diabetes is characterized, in part, by activation of toxic oxidative and glycoxidative pathways that are triggered by persistent hyperglycemia and contribute to diabetic complications. Inhibition of these pathways may benefit diabetic patients by delaying the onset of complications. One such inhibitor, pyridoxamine (PM), had shown promise in clinical trials. However, the mechanism of PM action in vivo is not well understood. We have previously reported that hypohalous acids can cause disruption of the structure and function of renal collagen IV in experimental diabetes (K.L. Brown et al., Diabetes 64:2242-2253, 2015). In the present study, we demonstrate that PM can protect protein functionality from hypochlorous and hypobromous acid-derived damage via a rapid direct reaction with and detoxification of these hypohalous acids. We further demonstrate that PM treatment can ameliorate specific hypohalous acid-derived structural and functional damage to the renal collagen IV network in a diabetic animal model. These findings suggest a new mechanism of PM action in diabetes, namely sequestration of hypohalous acids, which may contribute to known therapeutic effects of PM in human diabetic nephropathy.

Copyright © 2015 Elsevier Inc. All rights reserved.

MeSH Terms (20)

Amino Acid Sequence Animals Bromates Chromatography, Liquid Collagen Type IV Diabetes Mellitus, Experimental Humans Hypochlorous Acid In Vitro Techniques Kidney Male Molecular Sequence Data Oxidants Oxidation-Reduction Proteolysis Pyridoxamine Rats Rats, Sprague-Dawley Tandem Mass Spectrometry Vitamin B Complex

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