The effect of exercise on Myocardial Na+/H+ exchanger-1 (NHE1)

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)

Bryan James Feger (Creator)

Institution

The University of North Carolina at Greensboro (UNCG )

Web Site: http://library.uncg.edu/

Advisor

Joseph Starnes

Abstract: The myocardial Na+/H+ exchanger–1 (NHE1) plays a major role in regulation of intracellular pH and its upregulation has been implicated in increased ischemia–reperfusion injury and other pathologies. Hydrogen peroxide (H₂O₂) is a major by–product of reperfusion and is known to enhance NHE1 activity via ERK1/2 signaling. However, neither NHE1 activity nor its regulation by H₂O₂ has been examined in response to exercise. Therefore, we examined the effect of aerobic exercise training on intrinsic NHE1 activity, H₂O₂–mediated activation of NHE1, and H₂O₂–induced phosphorylation of ERK1/2 using isolated adult ventricular myocytes. Adult female Sprague–Dawley rats were randomly divided into sedentary (S, n=10) and exercise–trained (E, n=8) groups. Heart weight:body weight and plantaris muscle cytochrome c oxidase activity was significantly greater by 6.8% and 1.9 fold, respectively, in E animals compared to S animals. NHE1 activity was determined in cells loaded with the pH fluoroprobe 2’,7’–bis –(2 –carboxyethyl)–5 –(and –6)–carboxyfluorescein (BCECF). NHE1 activity was 161% greater in E myocytes compared to S myocytes (0.57 ± 0.10 v 1.49 ± 0.18 fmol/min), which is attributed to the 55% greater cell volume (22.2 ± 0.6 v 34.3 ± 1.1 pL) and 48% greater buffering capacity (28.79 ± 0.72 v 42.65 ± 0.79 mM/pH unit) of E cells. Stimulation with H_vO₂ enhanced NHE1 activity in S and E but to a significantly lower level in E myocytes (1.55 v 0.64 fold). As assessed by Western blotting, H₂O₂ stimulation also increased phosphorylation of ERK1/2. There was no difference in the density of H₂O₂–stimulated phosphorylation between S and E; however, E myocytes were observed to have significantly less total ERK1/2. No difference was observed in either cardiomyocyte NHE1 content or catalase and glutathione peroxidase activity. Our data indicate that aerobic exercise training increases NHE1 activity at physiological intracellular pH and attenuates the H₂O₂–mediated activation of NHE1 activity.

The effect of exercise on Myocardial Na+/H+ exchanger-1 (NHE1)
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Created on 12/1/2012
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Additional Information

Publication

Dissertation

Language: English

Date: 2012

Keywords

Buffering capacity, Exercise training, Extracellular signal-regulated kinase 1/2, Hydrogen peroxide, Na+/H+ exchanger-1

Subjects

Exercise $x Physiological aspects

Cardiovascular system $x Research

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