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

Hartman Madu, Josh Avance, Sergei Chetyrkin, Carl Darris, Kristie Lindsey Rose, Otto A. Sanchez, Billy Hudson, Paul Voziyan

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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., Diabetes64:2242-2253, 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.

Original languageEnglish (US)
Article number12505
Pages (from-to)83-90
Number of pages8
JournalFree Radical Biology and Medicine
Volume89
DOIs
StatePublished - Dec 1 2015

Keywords

  • Diabetes
  • Freeradicals
  • Hypobromous acid
  • Hypochlorous acid
  • Nephropathy
  • Posttranslational modifications
  • Protein halogenation
  • Pyridoxamine

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