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

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

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

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Madu, Hartman Avance, Josh Chetyrkin, Sergei Darris, Carl Rose, Kristie Lindsey Sanchez, Otto A. Hudson, Billy Voziyan, Paul
Description	Country affiliation: United States Author Affiliation: Madu H ( Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.); Avance J ( Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.); Chetyrkin S ( Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.); Darris C ( Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.); Rose KL ( Department of Biochemistry, Vanderbilt University Medical Center, Nashville, TN 37232, USA.); Sanchez OA ( Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN 37232, USA.); Hudson B ( Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA); Voziyan P ( Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: paul.voziyan@vanderbilt.edu.)
Abstract	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.
File Format	HTM / HTML
ISSN	08915849
Volume Number	89
e-ISSN	18734596
Journal	Free Radical Biology and Medicine
Language	English
Publisher	Elsevier
Publisher Date	2015-12-01
Publisher Place	United States
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Free radicals biology Collagen Type Iv Drug Effects Diabetes Mellitus, Experimental Prevention & Control Hypochlorous Acid Toxicity Kidney Proteolysis Pyridoxamine Pharmacology Vitamin B Complex Amino Acid Sequence Animals Bromates Chromatography, Liquid Chemistry Metabolism Pathology Humans In Vitro Techniques Male Molecular Sequence Data Oxidants Oxidation-reduction Rats Rats, Sprague-dawley Tandem Mass Spectrometry Journal Article Research Support, N.i.h., Extramural
Content Type	Text
Resource Type	Article
Subject	Physiology (medical) Biochemistry

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