Pyridoxamine protects proteins from damage by hypohalous acids in vitro and in vivo
| Autor: | Paul A. Voziyan, Carl Darris, Billy G. Hudson, Otto A. Sanchez, Hartman Madu, Josh Avance, Kristie L. Rose, Sergei V. Chetyrkin |
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| Rok vydání: | 2015 |
| Předmět: |
Collagen Type IV
Male Hypochlorous acid Molecular Sequence Data Oxidative phosphorylation In Vitro Techniques Pharmacology Kidney Biochemistry Article Diabetes Mellitus Experimental Nephropathy Rats Sprague-Dawley Diabetic nephropathy chemistry.chemical_compound Tandem Mass Spectrometry In vivo Physiology (medical) Diabetes mellitus medicine Animals Humans Amino Acid Sequence Bromates Protein halogenation Oxidants medicine.disease Hypochlorous Acid Rats chemistry Proteolysis Vitamin B Complex Pyridoxamine Oxidation-Reduction Chromatography Liquid |
| Zdroj: | Free Radical Biology and Medicine. 89:83-90 |
| ISSN: | 0891-5849 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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