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)

During the progression of certain degenerative conditions, including myocardial ischemia-reperfusion injury, mitochondria are a source of increased free-radical generation and exhibit declines in respiratory function(s). It has therefore been suggested that oxidative damage to mitochondrial components plays a critical role in the pathology of these processes. Polyunsaturated fatty acids of membrane lipids are prime molecular targets of free-radical damage. A major product of lipid peroxidation, 4-hydroxy-2-nonenal (HNE), is highly cytotoxic and can readily react with and damage protein. In this study, the effects of HNE on intact cardiac mitochondria were investigated to gain insight into potential mechanisms by which free radicals mediate mitochondrial dysfunction. Exposure of mitochondria to micromolar concentrations of HNE caused rapid declines in NADH-linked but not succinate-linked state 3 and uncoupled respiration. The activity of complex I was unaffected by HNE under the conditions of our experiments. Loss of respiratory activity reflected the inability of HNE-treated mitochondria to meet NADH demand during maximum rates of O2 consumption. HNE exerted its effects on intact mitochondria by inactivating alpha-ketoglutarate dehydrogenase. These results therefore identify a potentially important mechanism by which free radicals bring about declines in mitochondrial respiration.
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PMID:Inhibition of NADH-linked mitochondrial respiration by 4-hydroxy-2-nonenal. 942 76

Asperosaponin VI is a saponin of the medicinal herb Dipsacus asper (Xuduan), and no pharmacological activity has been reported yet. In this study, we investigated the anti-myocardial ischemia effects of Asperosaponin VI (ASA VI) both in vivo and in vitro. An animal model of myocardial ischemia(MI) injury was induced by coronary occlusion, pretreatment with ASA VI (10 and 20mg/kg, i.v.) could protect the heart from ischemia injury by decreasing the levels of creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), glutamic oxalacetic transaminase (GOT) and cardiac troponin T (cTnT) in serum, increasing the levels of catalase, glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) levels in heart, and decreasing that of malondialdehyde (MDA) level in acute MI rats. ASA VI also raised the activities of mitochondrial enzymes (succinate dehydrogenase (SDH), isocitrate dehydrogenase (ICDH), malate dehydrogenase (MDH) and alpha-ketoglutarate dehydrogenase (alpha-KGDH)) and those of adenosine triphosphate (ATP) content, but lowered Ca(2+) level. Electrocardiograph parameters and histopathological observations demonstrated the same protective effects. In vitro experiment, neonatal rat cardiomyocytes were incubated to test the direct cytoprotective effect of ASA VI against H(2)O(2) exposure. Pretreatment with ASA VI (30 and 60 microg/ml) prior to H(2)O(2) exposure increased cell viability and inhibited H(2)O(2)-induced reactive oxygen species increase. ASA VI (15, 30 and 60 microg/ml) also increased the activities of LDH in the cultured supernatant and SOD in cardiomyocytes, but decreased the cardiomyocytes MDA level. Our results suggested that ASA VI could provide significant cardioprotective effects against acute MI in rats. The mechanisms might be attributed to scavenging lipid peroxidation products and reactive oxygen species, increasing antioxidant defense enzymes and preventing mitochondrial damage.
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PMID:Protective roles of Asperosaponin VI, a triterpene saponin isolated from Dipsacus asper Wall on acute myocardial infarction in rats. 1990 36