Attention of Maitotoxin - Induced Cytotoxicity in Rat Aortic Smooth Muscle Cells by Inhibitors of Na+/Ca2+ Exchange, and Calpain Activation
- Authors
- Corporate Authors
- Defence R&D Canada - Suffield, Ralston ALTA (CAN)
- Abstract
- The highly potent marine toxin maitotoxin (MTX) evoked an increase in cytosolic Ca2+ levels in fura-2 loaded rat aortic smooth muscle cells, which was dependent on extracellular Ca2+. This increase was almost fully inhibited by KB-R7943, a potent selective inhibitor of the reverse mode of the Na+/Ca2+ exchanger (NCX). Cell viability was assessed using ethidium bromide uptake and the alamarBlue cytotoxicity assay. In both assays MTX-induced toxicity was attenuated by KB-R7943, as well as by MDL 28170, a membrane permeable calpain inhibitor. Maitotoxin-evoked contractions of rat aortic strip preparations in vitro, which persist following washout of the toxin, were relaxed by subsequent addition of KB-R7943 or MDL 28170, either in the presence of, or following washout of MTX. These results suggest that MTX targets the Na+/Ca2+ exchanger and causes it to operate in reverse mode (Na+ efflux/Ca2+ influx), thus leading to calpain activation, NCX cleavage, secondary Ca2+ overload and cell death.
- Report Number
- DRDC-SUFFIELD-SL-2007-227 — Scientific Literature
- Date of publication
- 06 Mar 2008
- Number of Pages
- 9
- DSTKIM No
- CA030928
- CANDIS No
- 529620
- Format(s):
- Electronic Document(PDF)
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