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1 Department of Pharmacology and Toxicology and 2 Department of Pathology, University of Western Ontario, London, Ontario, Canada N6A 5C1
Na+/H+
exchange (NHE) has been demonstrated to mediate myocardial
ischemia and reperfusion injury as well as injury produced by
hydrogen peroxide
(H2O2)
or lysophosphatidylcholine (LPC). However, changes in gene expression
in response to injurious factors have not been extensively studied. We
examined
Na+/H+
exchange isoform 1 (NHE-1) expression using Southern detection of the
RT-PCR product in response to 30 min of global ischemia with or
without reperfusion in isolated rat hearts or to 30 min of exposure to
either
H2O2
(100 µM) or LPC (5 µM). We also determined whether ischemic
preconditioning (2× 5-min ischemia) alters basal NHE-1
expression or the subsequent response to insult. Ischemia with
or without reperfusion increased NHE-1 expression approximately sevenfold (P < 0.05), whereas either
H2O2 or LPC increased expression approximately
twofold. Preconditioning reduced NHE-1 message by ~70%
(P < 0.05) and significantly
attenuated the effects of ischemia, H2O2,
or LPC. The internal standard,
-globin was unaffected by any
treatment. Our results indicate that NHE-1 expression is rapidly increased in response to ischemia with or without reperfusion as well as in response to
H2O2
or LPC. In contrast, preconditioning was associated with
downregulation of NHE-1. These results may be important in furthering
our understanding of NHE-1 in cardiac disease states and suggest that
the antiporter adapts rapidly to cardiac conditions associated with pathology.
ischemia-reperfusion; preconditioning; hydrogen peroxide; lysophosphatidylcholine
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