In:
Journal of Cellular and Molecular Medicine, Wiley, Vol. 17, No. 9 ( 2013-09), p. 1119-1127
Abstract:
Sarcolemmal Na + / H + exchanger 1 ( NHE 1) activity is essential for the intracellular pH (pH i ) homeostasis in cardiac myocytes. Emerging evidence indicates that sarcolemmal NHE 1 dysfunction was closely related to cardiomyocyte death, but it remains unclear whether defective trafficking of NHE 1 plays a role in the vital cellular signalling processes. Dynamin ( DNM ), a large guanosine triphosphatase ( GTP ase), is best known for its roles in membrane trafficking events. Herein, using co‐immunoprecipitation, cell surface biotinylation and confocal microscopy techniques, we investigated the potential regulation on cardiac NHE 1 activity by DNM . We identified that DNM 2, a cardiac isoform of DNM , directly binds to NHE 1. Overexpression of a wild‐type DNM 2 or a dominant‐negative DNM 2 mutant with defective GTP ase activity in adult rat ventricular myocytes ( ARVM s) facilitated or retarded the internalization of sarcolemmal NHE 1, whereby reducing or increasing its activity respectively. Importantly, the increased NHE 1 activity associated with DNM 2 deficiency led to ARVM s apoptosis, as demonstrated by cell viability, terminal deoxynucleotidyl transferase–mediated dUTP nick‐end labelling assay, Bcl‐1/Bax expression and caspase‐3 activity, which were effectively rescued by pharmacological inhibition of NHE 1 with zoniporide. Thus, our results demonstrate that disruption of the DNM 2‐dependent retrograde trafficking of NHE 1 contributes to cardiomyocyte apoptosis.
Type of Medium:
Online Resource
ISSN:
1582-1838
,
1582-4934
DOI:
10.1111/jcmm.2013.17.issue-9
Language:
English
Publisher:
Wiley
Publication Date:
2013
detail.hit.zdb_id:
2076114-4
Permalink