Amiloride derivatives induce apoptosis by depleting ER Ca(2+) stores in vascular endothelial cells.

ABSTRACT:

Background and purpose

Amiloride derivatives are blockers of the Na(+)/H(+) exchanger (NHE) and at micromolar concentrations have protective effects on cardiac and brain ischaemia/reperfusion injury but at higher concentrations also induce apoptosis. Here, we aimed to elucidate the mechanism related to this cytotoxic action.

Experimental approach

We quantified the expression of genes associated with endoplasmic reticulum (ER) stress and measured changes in luminal ER Ca(2+) concentration ([Ca(2+)](ER)) with a 'cameleon' indicator, D1ER.

Key results

Amiloride derivatives induced apoptosis in vascular endothelial cells, an effect that increased at alkaline extracellular pH. The potency order for cytotoxicity was 5-(N,N-hexamethylene)-amiloride (HMA) > 5-(N-methyl-N-isob

SUBMITTER: Park KS 

PROVIDER: S-EPMC2697743 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature