Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 microM) or LPC (5 microM). We also determined whether ischemic preconditioning (2x 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 approximately 70% (P < 0.05) and significantly attenuated the effects of ischemia, H2O2, or LPC. The internal standard, beta-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.
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PMID:Modulation of Na+/H+ exchange isoform 1 mRNA expression in isolated rat hearts. 1048 21

Bach1 is a transcriptional repressor of heme oxygenase-1 gene (Hmox-1) and beta-globin gene. Heme oxygenase (HO)-1 is an inducible cytoprotective enzyme that degrades pro-oxidant heme to carbon monoxide (CO) and biliverdin/bilirubin, which are thought to mediate anti-inflammatory and anti-oxidant actions of HO-1. In the present study, we investigated the role of Bach1 in tissue protection against myocardial ischemia/reperfusion (I/R) injury in vivo using mice lacking the Bach1 gene (Bach1(-/-)) and wild-type (Bach1(+/+)) mice. In Bach1(-/-) mice, myocardial expression of HO-1 protein was constitutively up-regulated by 3.4-fold compared to that in Bach1(+/+) mice. While myocardial I/R induced HO-1 protein in ischemic myocytes in both strains of mice, the extent of induction was significantly greater in Bach1(-/-) mice than in Bach1(+/+) mice. Myocardial infarction was markedly reduced in size by 48.4% in Bach1(-/-) mice. Pretreatment of Bach1(-/-) mice with zinc-protoporphyrin, an inhibitor of HO activity, abolished the infarction-reducing effect of Bach1 disruption, indicating that reduction in the infarct size was mediated, at least in part, by HO-1 activity. Thus, Bach1 plays a pivotal role in setting the levels of both constitutive and inducible expression of HO-1 in the myocardium. Bach1 inactivation during I/R appears to be a key mechanism controlling the activation level of cytoprotective program involving HO-1.
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PMID:Genetic ablation of the transcription repressor Bach1 leads to myocardial protection against ischemia/reperfusion in mice. 1682 98

Hippophae rhamnoides or seabuckthorn is used extensively in Indian and Tibetan traditional medicine for the treatment of circulatory disorders, ischemic heart disease, hepatic injury, and neoplasia. In the present study, we have evaluated the radioprotective potential of REC-1001, a fraction isolated from the berries of H. rhamnoides. Chemical analysis of the extract indicated that REC-1001 was approximately 68% by weight polyphenols, and contained kaempferol, isorhamnetin, and quercetin. The effect of REC-1001 on modulating radiation-induced DNA damage was determined in murine thymocytes by measuring nonspecific nuclear DNA damage at the whole genome level using the alkaline halo assay and by measuring sequence/gene-specific DNA damage both in nuclear DNA (beta-globin gene) and in mitochondrial DNA using a quantitative polymerase chain reaction. Treatment with 10 Gy resulted in a significant amount of DNA damage in the halo assay and reductions in the amplification of both the beta-globin gene and mitochondrial DNA. REC-1001 dose-dependently reduced the amount of damage detected in each assay, with the maximum protective effects observed at the highest REC-1001 dose evaluated (250 micro g/ml). Studies measuring the nicking of naked plasmid DNA further established the radioprotective effect of REC-1001. To elucidate possible mechanisms of action, the antioxidant properties and the free-radical scavenging activities of REC-1001 were evaluated. REC-1001 dose-dependently scavenged radiation-induced hydroxyl radicals, chemically-generated superoxide anions, stabilized DPPH radicals, and reduced Fe(3+) to Fe(2+). The results of the study indicate that the REC-1001 extract of H. rhamnoides protects mitochondrial and genomic DNA from radiation-induced damage. The polyphenols/flavonoids present in the extract might be responsible for the free radical scavenging and DNA protection afforded by REC-1001.
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PMID:Protection from radiation-induced mitochondrial and genomic DNA damage by an extract of Hippophae rhamnoides. 1694 57