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Departments of Surgery and Pathology, University of Colorado Health Sciences Center, Denver, Colorado 80262
Lipopolysaccharide (LPS) preconditioning induces cardiac
resistance to subsequent LPS or ischemia. This study tested the
hypothesis that resistance to LPS and resistance to ischemia
are two manifestations of cardiac cross-resistance which may involve
reprogramming of cardiac gene expression. Rats were preconditioned with
a single dose of LPS (0.5 mg/kg ip). Cardiac resistance to LPS was
examined with a subsequent LPS challenge. Cardiac resistance to
ischemia was determined by subjecting hearts to
ischemia-reperfusion. Total RNA was extracted from myocardium
for Northern analysis of mRNAs encoding protooncoproteins, antioxidant
enzymes, and contractile protein isoforms. Rats preconditioned with LPS
1-7 days earlier acquired cardiac resistance to endotoxemic
depression. This resistance temporally correlated with resistance to
ischemia. Pretreatment with cycloheximide (0.5 mg/kg ip)
abolished resistance to both LPS and ischemia. LPS
preconditioning induced the expression of c-jun and
c-fos mRNAs. LPS also transiently
increased mRNAs encoding catalase and Mn-containing superoxide
dismutase. The expression of both
- and
-myosin heavy chain mRNAs
was upregulated, whereas the expression of cardiac
-actin mRNA was
suppressed. We conclude that 1)
LPS induces sustained cardiac resistance to both LPS and ischemia, 2) resistance to
ischemia and resistance to LPS seem to be two mechanistically
indistinct components of cardiac cross-resistance, and
3) the cardiac cross-resistance is
associated with reprogramming of myocardial gene expression.
endotoxin; ischemia; protooncogenes; contractile protein isogenes; mRNA
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