Abstract
Activation of Na+/H+‐exchanger‐1: a novel mechanism in diabetic neuropathy
The FASEB journal, Vol.20(5), pp.A1417-A1417
03/2006
DOI: 10.1096/fasebj.20.5.A1417-a
Abstract
Enhanced Na+/H+‐exchange (NHE) results in cytosol alkalinization and activation of the upper part of glycolysis which, under conditions of diabetes‐associated inhibition or insufficient upregulation of glyceraldehyde 3‐phosphate dehydrogenase, causes diversion of the glycolytic flux towards several pathways implicated in diabetic complications. We explored the role for Na+/H+‐exchanger‐1 (NHE‐1), the most abundant NHE isoform, in DN. The specific NHE‐1 inhibitor, cariporide, prevented nerve blood flow (microelectrode polarography/hydrogen clearance) and sensory nerve conduction velocity (SNCV) deficits, and alleviated motor nerve conduction velocity (MNCV) deficit, thermal hyperalgesia (paw withdrawal and tail flick tests), mechanical hyperalgesia (von Frey anesthesiometer/rigid filament, and Randall‐Sellito tests) and tactile allodynia (flexible von Frey filaments) in STZ‐diabetic rats. MNCV deficit, thermal and mechanical hypoalgesia and tactile allodynia were less severe in NHE+/− than in NHE‐1+/+ STZ‐diabetic mice. High glucose‐induced NHE‐1 mRNA and protein overexpression (real‐time PCR and Western blotting) and NHE activation (BCECF fluorescence) were clearly manifest in human Schwann cells (HSC), and were mediated via poly (ADP‐ribose) polymerase‐1 (PARP‐1) and MAPK (ERK, SAPK/JNK)‐involved mechanisms. PARP‐1 activation and increased MAPK phosphorylation were detected within ~12–24 h of HSC exposure to 30 mM glucose. In conclusion, NHE‐1 activation is a novel fundamental mechanism in the pathogenesis of DN.
Details
- Title: Subtitle
- Activation of Na+/H+‐exchanger‐1: a novel mechanism in diabetic neuropathy
- Creators
- Irina G. Obrosova - Louisiana State University SystemOlga Ilnytska - Louisiana State University SystemNazar Mashtalir - Louisiana State University SystemFulu Bai - Louisiana State University SystemMark A. Yorek - Veterans Affairs Medical CenterViktor R. Drel - Louisiana State University System
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.20(5), pp.A1417-A1417
- Publisher
- Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.20.5.A1417-a
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Language
- English
- Date published
- 03/2006
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984363559602771
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