Attention of Maitotoxin - Induced Cytotoxicity in Rat Aortic Smooth Muscle Cells by Inhibitors of Na+/Ca2+ Exchange, and Calpain Activation

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Authors
  1. Frew, R.
  2. Wang, Y.
  3. Weiss, T.M.
  4. Nelson, P.
  5. Sawyer, T.W.
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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