Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many cardiac interventional procedures, such as coronary angioplasty, stenting, and thrombolysis, attempt to reintroduce blood flow (reperfusion) to an ischemic region of myocardium. However, the reperfusion is accompanied by a complex cascade of cellular and molecular events resulting in oxidative damage, termed myocardial ischemia-reperfusion (I/R) injury. In this study, we evaluated the ability of HO-4038, an N-hydroxypiperidine derivative of verapamil, on the modulation of myocardial tissue oxygenation (Po(2)), I/R injury, and key signaling molecules involved in cardioprotection in an in vivo rat model of acute myocardial infarction (MI). MI was created in rats by ligating the left anterior descending coronary artery (LAD) for 30 min followed by 24 h of reperfusion. Verapamil or HO-4038 was infused through the jugular vein 10 min before the induction of ischemia. Myocardial Po(2) and the free-radical scavenging ability of HO-4038 were measured using electron paramagnetic resonance spectroscopy. HO-4038 showed a significantly better scavenging ability of reactive oxygen radicals compared with verapamil. The cardiac contractile functions in the I/R hearts were significantly higher recovery in HO-4038 compared with the verapamil group. A significant decrease in the plasma levels of creatine kinase and lactate dehydrogenase was observed in the HO-4038 group compared with the verapamil or untreated I/R groups. The left ventricular infarct size was significantly less in the HO-4038 (23 +/- 2%) compared with the untreated I/R (36 +/- 4%) group. HO-4038 significantly attenuated the hyperoxygenation (36 +/- 1 mmHg) during reperfusion compared with the untreated I/R group (44 +/- 2 mmHg). The HO-4038-treated group also markedly attenuated superoxide production, increased nitric oxide generation, and enhanced Akt and Bcl-2 levels in the reperfused myocardium. Overall, the results demonstrated that HO-4038 significantly protected hearts against I/R-induced cardiac dysfunction and damage through the combined beneficial actions of calcium-channel blocking, antioxidant, and prosurvival signaling activities.
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PMID:Cardioprotection by HO-4038, a novel verapamil derivative, targeted against ischemia and reperfusion-mediated acute myocardial infarction. 1897 91

Recent observations have suggested that Ras signaling includes combinations of extracellular-signal-regulated Ras activation at the plasma membrane and endomembranes, and translocation of Ras from the plasma membrane to intracellular compartments. In this study we have shown that social isolation of rat decreases the content of Bcl-2-associated K-Ras in hippocampal mitochondria, whereas the amount of H-Ras is increased in the microsomal fraction. Furthermore, we have found that galectin 1, a binding partner of activated Ras, was increased in the soluble fractions. The redistribution of Ras isoforms was accompanied by acceleration in mitochondrial hexokinase and inhibition of mitochondrial aconitase, succinate dehydrogenase, and creatine kinase, whereas the activity of aldolase, as well as cytoplasmic creatine kinase was not changed. Our data suggest that inhibition of mitochondrial oxidative metabolism by reactive oxygen species (ROS) and compensatory elevation of glycolysis in hippocampus occurs during social isolation of rats and Ras trafficking could play an important role in switching of impaired oxidative phosphorylation to anaerobic glycolysis.
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PMID:Social isolation in rats inhibits oxidative metabolism, decreases the content of mitochondrial K-Ras and activates mitochondrial hexokinase. 1961 40

The therapy for acute myocardial infarction (AMI) has been improved; yet, AMI remains a major cause of death and heart failure in industrialized countries. B-type natriuretic peptide (BNP), a hormone secreted from the heart, has been shown cardioprotective effects during myocardial ischemia/reperfusion. In the present study, we aimed to examine whether BNP could inhibit myocardial apoptosis during ischemia/reperfusion. Rabbits were randomly divided into three groups (12 animals for each group): sham-operated control and ischemia-reperfusion animals with or without BNP treatment. Occlusion of the left circumflex coronary for 45 min was followed by 3-h reperfusion with infusion of physiological saline (untreated group) or BNP (treated group) starting 5 min before reperfusion and throughout the whole reperfusion. The infarct size, measured by triphenyltetrazolium chloride staining, was reduced by 44% with BNP treatment (P < 0.01). Accordingly, serum levels of creatine kinase and lactate dehydrogenase were markedly reduced in BNP-treated group (P < 0.05) compared with the untreated group. BNP significantly attenuated apoptotic cells (TUNEL-positive cardiomyocyte nuclei) in the myocardium (P < 0.01). The BNP-mediated attenuation of apoptosis was associated with the increased expression of an anti-apoptotic protein Bcl-2 and the reduced expression of a pro-apoptotic protein Bax. Moreover, BNP treatment significantly decreased the magnitude of caspase-3 activation caused by myocardial ischemia-reperfusion. In conclusion, pretreatment with BNP shortly before the onset of reperfusion not only reduces necrosis, but also attenuates myocardial apoptosis. BNP appears to be an ideal pharmacological agent applied as an adjuvant therapy to current myocardial reperfusion strategies.
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PMID:Pretreatment with B-type natriuretic peptide protects the heart from ischemia-reperfusion injury by inhibiting myocardial apoptosis. 1977 27

(2E)-2-{6-[(E)-2-carboxyvinyl]-2,3-dihydroxyphenyl}-3-(3,4-dihydroxyphenyl) propenoic acid, a novel compound designated SMND-309, is a new derivate of salvianolic acid B. The present study was designed to investigate the cardioprotective potential of SMND-309 and to elucidate the possible mechanisms on the basis of biochemical, histopathological and immunohistochemical studies in a rat model of acute myocardial infarction induced by permanent ligation of the left coronary artery. The results showed that treatment with SMND-309 via tail vein at doses of 10 and 20 mg/kg significantly prevented the elevation in ST segment level and the increase in serum creatine kinase-MB, lactate dehydrogenase, alanine aminotransferase and cardiac troponin T content. Meanwhile, SMND-309 significantly increased the activities of superoxide dismutase, catalase and glutathione peroxidase, decreased the content of malondialdehyde in myocardium, and reduced the myocardium necrosis scores and the number of apoptosis cardiocytes in accordance with the up-regulated expression of anti-apoptotic protein, Bcl-2 and the down-regulated expression of proapoptotic protein, Bax. Moreover, SMND-309 exhibits significantly higher potency compared to salvianolic acid B at the same mg/kg but not the same mol/kg. These findings indicate that SMND-309 has a protective potential against myocardial infarction injury and the protective effects may be due to its scavenging lipid peroxidation products, increasing endogenous antioxidant defence enzymes and attenuating cardiocyte apoptosis.
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PMID:Cardioprotective effect of SMND-309, a novel derivate of salvianolic acid B on acute myocardial infarction in rats. 1991 62

Transgenic mice expressing human mutated superoxide dismutase 1 (SOD1) linked to familial forms of amyotrophic lateral sclerosis are frequently used as a disease model. We used the SOD1G93A mouse in a cross-breeding strategy to study the function of physiological prion protein (Prp). SOD1G93APrp-/- mice exhibited a significantly reduced life span, and an earlier onset and accelerated progression of disease, as compared with SOD1G93APrp+/+ mice. Additionally, during disease progression, SOD1G93APrp-/- mice showed impaired rotarod performance, lower body weight, and reduced muscle strength. Histologically, SOD1G93APrp-/- mice showed reduced numbers of spinal cord motor neurons and extended areas occupied by large vacuoles early in the course of the disease. Analysis of spinal cord homogenates revealed no differences in SOD1 activity. Using an unbiased proteomic approach, a marked reduction of glial fibrillary acidic protein and enhanced levels of collapsing response mediator protein 2 and creatine kinase were detected in SOD1G93APrp-/- versus SOD1G93A mice. In the course of disease, Bcl-2 decreases, nuclear factor-kappaB increases, and Akt is activated, but these changes were largely unaffected by Prp expression. Exclusively in double-transgenic mice, we detected a significant increase in extracellular signal-regulated kinase 2 activation at clinical onset. We propose that Prp has a beneficial role in the SOD1G93A amyotrophic lateral sclerosis mouse model by influencing neuronal and/or glial factors involved in antioxidative defense, rather than anti-apoptotic signaling.
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PMID:Neuroprotective function of cellular prion protein in a mouse model of amyotrophic lateral sclerosis. 2007 2

The aim of the study was to investigate the cardioprotective effect and mechanism of Crataegus oxycantha (COC) extract, a well-known natural antioxidant-based cardiotonic, against ischemia/reperfusion (I/R) injury. Electron paramagnetic resonance studies showed that COC extract was capable of scavenging superoxide, hydroxyl, and peroxyl radicals, in vitro. The cardioprotective efficacy of the extract was studied in a crystalloid perfused heart model of I/R injury. Hearts were subjected to 30min of global ischemia followed by 45min of reperfusion. During reperfusion, COC extract was infused at a dose rate of 1mg/ml/min for 10min. Hearts treated with COC extract showed a significant recovery in cardiac contractile function, reduction in infarct size, and decrease in creatine kinase and lactate dehydrogenase activities. The expressions of xanthine oxidase and NADPH oxidase were significantly reduced in the treated group. A significant upregulation of the anti-apoptotic proteins Bcl-2 and Hsp70 with simultaneous downregulation of the pro-apoptotic proteins cytochrome c and cleaved caspase-3 was observed. The molecular signaling cascade including phospho-Akt (ser-473) and HIF-1alpha that lead to the activation or suppression of apoptotic pathway also showed a significant protective role in the treatment group. No significant change in phospho-p38 levels was observed. The results suggested that the COC extract may reduce the oxidative stress in the reperfused myocardium, and play a significant role in the inhibition of apoptotic pathways leading to cardioprotection.
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PMID:Cardioprotective properties of Crataegus oxycantha extract against ischemia-reperfusion injury. 2017 Oct 68

Telmisartan, an angiotensin II-receptor blocker (ARB), is a partial agonist of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma). We investigated whether telmisartan improved the pathophysiology of myocardial infarction in diabetes partially through the PPAR-gamma pathway by assessing a variety of indices, e.g., hemodynamic, biochemical, histoarchitectural changes, and apoptosis. Diabetes was induced by a single dose of streptozotocin (70 mg/kg, IP). Diabetic rats received either telmisartan (10 mg/kg/day, orally), the PPAR-gamma antagonist GW9662 (1 mg/kg/day, IP), or both for 14 days with concurrent administration of isoproterenol (85 mg/kg, SC) on days 13 and 14. Compared with diabetic controls, diabetic rats with myocardial infarction exhibited altered hemodynamic profiles and reduction in the activities of creatine kinase-MB isoenzyme, lactate dehydrogenase, superoxide dismutase, catalase, and glutathione level along with increased level of malondialdehyde in the heart. Further, diabetic animals with myocardial infarction exhibited increased myonecrosis, edema, and apoptotic cell death. Treatment with telmisartan significantly improved the redox status of the myocardium with subsequent cardiac functional recovery. However, significant effects were lowered in animals treated with telmisartan plus GW9662. Telmisartan markedly inhibited Bax expression, TUNEL-positive cells, myonecrosis, and edema. On the other hand, administration of telmisartan plus GW9662 did not elicit the same effects, nor did they increase Bcl-2 protein expression in isoproterenol-induced myocardially infarcted diabetic rats when administered concomitantly or individually. Moreover, down-regulated PPAR-gamma expression in myocardially infarcted diabetic hearts was increased by telmisartan treatment. In addition to class effects of ARBs, telmisartan reduces oxidative stress and apoptosis and improves cardiac function via the PPAR-gamma pathway.
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PMID:Modulation of PPAR-gamma by telmisartan protects the heart against myocardial infarction in experimental diabetes. 2030 15

To determine whether ferilnic nirate (FLNT) can precondition the rat heart against myocardial ischemia/reperfusion (I/R) damage and its mechanism, two groups of experiments were conducted. In the first group of experiments, rats were divided among four treatment groups: sham group; solvent with I/R (I/R control group); FLNT pretreatment with I/R (I/R FLNT group); and late ischemic preconditioning group (LPC group). In the second group of experiments without I/R, rats were divided into two treatment groups: control group and FLNT group. The results indicated that myocardial infarct size and the levels of creatine kinase and lactate dehydrogenase in the sera of the I/R FLNT group were significantly lower and the level of nitric oxide molecule and Mn-containing superoxide dismutase were significantly elevated in the heart tissue compared with I/R control group. The protein expression ratio of Bcl-2/Bax in heart tissue was significantly elevated in the I/R FLNT group. These results demonstrate FLNT is able to precondition rat hearts against myocardial ischemia/reperfusion damage to a similar level as that achieved via the late phase of ischemic preconditioning. The mechanism may involve the up-regulation of nitric oxide and the strengthening of anti-oxidant and anti-apoptosis cellular functions.
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PMID:Ferilnic nirate produces delayed preconditioning against myocardial ischemia and reperfusion injury in rats. 2060 93

Cardiomyocyte apoptosis plays a critical role in the progress of heart diseases. Asperosaponin VI (ASA VI), a triterpene saponin isolated from Dipsacus asper Wall, has shown cardioprotective effects in vivo. However, whether ASA VI has a protective effect against cardiomyocyte apoptosis is poorly understood. The present study was aimed to investigate the cardioprotective role of ASA VI and the underlying mechanisms in hypoxia-induced cardiomyocyte apoptosis. Cardiomyocytes were exposed to hypoxic condition for 6 h and then cell viability markedly decreased, lactate dehydrogenase (LDH) and creatine phosphokinase (CK) activities in the culture supernatant significantly increased. Hypoxia-activated apoptosis were confirmed by Hoechst 33258 nuclear staining and Annexin V-FITC staining. These changes were associated with the decrease of the Bcl-2/Bax ratio, active caspase-3 expression, phosphorylations of Akt and cAMP response element-binding protein (CREB). Moreover, ASA VI significantly attenuated increased LDH and CK activities, and increased cell viability in hypoxia treated myocytes in a dose-dependent fashion. Hoechst 33258 nuclear staining and Annexin V-FITC staining observations demonstrated the same protective effects. ASA VI treatment inhibited apoptosis in hypoxia-induced cardiomyocyte by increasing the Bcl-2/Bax ratio and decreasing active caspase-3 expression, as well as enhancing of p-Akt and p-CREB. Furthermore, the protective effects of ASA VI were prevented by phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 treatment. In consequence, we demonstrated that ASA VI had protective effect against hypoxia-induced cardiomyocytes apoptosis probably by activating the PI3K/Akt and CREB pathways.
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PMID:Asperosaponin VI protects cardiac myocytes from hypoxia-induced apoptosis via activation of the PI3K/Akt and CREB pathways. 2086 24

This study was designed to investigate the therapeutic effect of sodium formononetin-3'-sulphonate (Sul-F), a water-soluble derivate of formononetin, on acute myocardial infarction in rats. The results showed that treatment with Sul-F significantly prevented the elevation of ST-segment level, decreased the contents of creatine kinase-MB, lactate dehydrogenase, alanine aminotransferase and cardiac troponin T in serum and reduced the myocardium necrosis scores. The number of apoptosis cardiocytes is well accordance with the up-regulated expression of Bcl-2 and the down-regulated expression of Bax. Meanwhile, Sul-F significantly increased the cardiac mitochondrial ATP content, improved ATP synthase activity, decreased thiobarbituric acid-reactive substances content and attenuated the decrease in superoxide dismutase and glutathione peroxidase activities. These findings indicate that Sul-F has a protective potential against myocardial infarction injury. A possible mechanism for the protective effect is the elevated expression of endogenous antioxidant defence enzymes degraded lipid peroxidation products and improved energy metholism of cardiac mitochondrial, thus attenuating cardiocyte apoptosis.
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PMID:Cardioprotective effect of sulphonated formononetin on acute myocardial infarction in rats. 2123 20


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