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10.1152/ajpheart.00422.2004

http://scihub22266oqcxt.onion/10.1152/ajpheart.00422.2004
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15284066!ä!15284066

suck abstract from ncbi


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pmid15284066      Am+J+Physiol+Heart+Circ+Physiol 2004 ; 287 (6): H2369-75
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  • Cobalt chloride induces delayed cardiac preconditioning in mice through selective activation of HIF-1alpha and AP-1 and iNOS signaling #MMPMID15284066
  • Xi L; Taher M; Yin C; Salloum F; Kukreja RC
  • Am J Physiol Heart Circ Physiol 2004[Dec]; 287 (6): H2369-75 PMID15284066show ga
  • Acute systemic hypoxia induces delayed cardioprotection against ischemia (I)-reperfusion (R) injury via inducible nitric oxide synthase (iNOS)-dependent mechanism. Because CoCl2 is known to elicit hypoxia-like responses, we hypothesized that this chemical would mimic the delayed preconditioning effect in the heart. Adult male mice were pretreated with CoCl2 or saline. The hearts were isolated 24 h later and subjected to 20 min of global I and 30 min of R in Langendorff mode. Myocardial infarct size (% of risk area; mean +/- SE, n=6-8/group) was reduced in mice pretreated with 30 mg/kg CoCl2 (16.1 +/- 3.1% vs. 27.6 +/- 3.3% with saline control; P <0.05) without compromising postischemic cardiac function. Higher doses of CoCl2 failed to induce similar protection. Electrophoretic mobility gel shift assay demonstrated significant enhancement in DNA binding activity of hypoxia-inducible factor 1alpha (HIF-1alpha) and activator protein 1 (AP-1) in nuclear extracts from CoCl2-treated hearts. Activation of HIF-1alpha and AP-1 was evident at 30 min and sustained for the next 4 h after CoCl2 injection. In contrast, CoCl2-induced protection was independent of NF-kappaB activation because no DNA binding or p65 translocation was observed in nuclear extracts. Also, CoCl2-induced cardioprotection was preserved in p50 subunit NF-kappaB-knockout (KO) mice (11.1 +/- 3.0% vs. 25.1 +/- 5.0% in saline-treated p50-KO mice; P <0.05). The infarct-limiting effect of CoCl2 was absent in iNOS-KO mice (20.9 +/- 3.0%). We conclude that in vivo administration of CoCl2 preconditions the heart against I/R injury. The delayed protective effect of CoCl2 is achieved through a distinctive signaling mechanism involving HIF-1alpha, AP-1, and iNOS but independent of NF-kappaB activation.
  • |Animals[MESH]
  • |Animals, Outbred Strains[MESH]
  • |Antimutagenic Agents/*pharmacology[MESH]
  • |Cobalt/*pharmacology[MESH]
  • |Coronary Circulation[MESH]
  • |DNA/metabolism[MESH]
  • |Hypoxia-Inducible Factor 1, alpha Subunit[MESH]
  • |Ischemic Preconditioning, Myocardial/*methods[MESH]
  • |Male[MESH]
  • |Mice[MESH]
  • |Mice, Inbred ICR[MESH]
  • |Myocardial Reperfusion Injury/drug therapy/metabolism/mortality[MESH]
  • |Nitric Oxide Synthase Type II[MESH]
  • |Nitric Oxide Synthase/*metabolism[MESH]
  • |Transcription Factor AP-1/*metabolism[MESH]


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