Journal article
Peroxynitrite and Protein Nitration in the Pathogenesis of Diabetic Peripheral Neuropathy
Diabetes/metabolism research and reviews, Vol.30(8), pp.669-678
11/01/2014
DOI: 10.1002/dmrr.2549
PMCID: PMC4177961
PMID: 24687457
Abstract
Peroxynitrite, a product of the reaction of superoxide with nitric oxide, causes oxidative stress with concomitant inactivation of enzymes, poly(ADP-ribosylation), mitochondrial dysfunction, impaired stress signaling, as well as protein nitration. In this study we sought to determine the effect of preventing protein nitration or increasing peroxynitrite decomposition on diabetic neuropathy in mice after an extended period of untreated diabetes. C57Bl6/J male control and diabetic mice were treated with the peroxynitrite decomposition catalyst Fe(III) tetramesitylporphyrin octasulfonate (FeTMPS, 10 mg/kg/d) or protein nitration inhibitor (−)-epicatechin gallate (20 mg/kg/d) for 4 weeks, after an initial 28 weeks of hyperglycemia. Untreated diabetic mice developed motor and sensory nerve conduction velocity deficits, thermal and mechanical hypoalgesia, tactile allodynia, and loss of intraepidermal nerve fibers. Both FeTMPS and epicatechin gallate partially corrected sensory nerve conduction slowing and small sensory nerve fiber dysfunction without alleviation of hyperglycemia. Correction of motor nerve conduction deficit and increase in intraepidermal nerve fiber density were found with FeTMPS treatment only. In conclusion, peroxynitrite injury and its component, protein nitration, are implicated in the development of diabetic peripheral neuropathy. The findings indicate that both structural and functional changes of chronic diabetic peripheral neuropathy can be reversed, and provide rationale for the development of a new generation of antioxidants and peroxynitrite decomposition catalysts, for treatment of diabetic peripheral neuropathy.
Details
- Title: Subtitle
- Peroxynitrite and Protein Nitration in the Pathogenesis of Diabetic Peripheral Neuropathy
- Creators
- Roman Stavniichuk - National Academy of Sciences of UkraineHanna Shevalye - Iowa City VA Health Care SystemSergey Lupachyk - Iowa City VA Health Care SystemAlexander Obrosov - Iowa City VA Health Care SystemJohn T. Groves - Princeton UniversityIrina G. Obrosova - National Academy of Sciences in UkraineMark A. Yorek - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Diabetes/metabolism research and reviews, Vol.30(8), pp.669-678
- DOI
- 10.1002/dmrr.2549
- PMID
- 24687457
- PMCID
- PMC4177961
- ISSN
- 1520-7552
- eISSN
- 1520-7560
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: DK081147-05; DOI: 10.13039/100000002, name: National Institutes of Health, award: DK073990-06; DOI: 10.13039/100000057, name: National Institute of General Medical Sciences, award: GM036298; DOI: 10.13039/100000738, name: U.S. Department of Veterans Affairs, award: BX001680-03
- Language
- English
- Date published
- 11/01/2014
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine; Ophthalmology and Visual Sciences
- Record Identifier
- 9984359686502771
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