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)

The aim of our study was to investigate the effect of Patrinia scabra Bunge polysaccharide (PSB-P2) on cervical cancer cell (U14)-bearing mice. The tumor weight of mice treated with PSB-P2 (40, 80 mg/kg b.w.) was significantly lower than that of the control group and serum lactate dehydrogenase (LDH) activity was decreased, while serum alkaline phosphatase (AKP) level was only changed slightly. Meanwhile, the number of apoptotic tumor cells was significantly increased in the mice by the treatment of PSB-P2 (40, 80 mg/kg b.w.). At the same time, cell cycle analysis showed the accumulation of tumor cells in the G0/G1 phase and a relative decrease in the S phase. On the other hand, using the reverse transcription-polymerase chain reaction (RT-PCR) assay, PSB-P2 (40, 80 mg/kg b.w.) showed the up-regulation of p53 and Bax, and significant inhibition of Bcl-2 in tumor tissues. It suggests a possible mechanism of the inhibitory effect of PSB-P2 on tumor growth.
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PMID:Anti-tumor activity of polysaccharides isolated from Patrinia scabra Bunge on U14 cervical carcinoma bearing mice. 1988 53

(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

In the present study, we examined the ability of a chemically synthesized compound based on the structure of leonurine, a phytochemical component of Herba leonuri, to protect H9c2 rat ventricular cells from apoptosis induced by hypoxia and serum deprivation, as a model of ischemia. The results revealed a concentration-dependent increase in cell viability associated with leonurine treatment, accompanied by a consistent decline in lactate dehydrogenase leakage into the culture medium. The fraction of annexin V-fluorescein isothiocyanate-positive cells was increased by hypoxia but reduced by leonurine. These changes were associated with increased expression of the antiapoptotic gene, Bcl-2, and reduced expression of the proapoptotic gene, Bax. Leonurine also reduced the cytosolic Ca overload induced by hypoxia. These results suggest that leonurine elicits potent cardioprotective effects in H9c2 cells, and these effects may be mediated by inhibition of intracellular Ca overload and apoptosis during hypoxia.
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PMID:4-Guanidino-n-butyl syringate (Leonurine, SCM 198) protects H9c2 rat ventricular cells from hypoxia-induced apoptosis. 1994 Jun 42

Reactive oxygen species are important mediators that exert a toxic effect during ischemia-reperfusion (I/R) injury of various organs. Sulforaphane is known to be an indirect antioxidant that acts by inducing Nrf2-dependent phase 2 enzymes. In this study, we investigated whether sulforaphane protects heart against I/R injury. Sprague-Dawley rats received sulforaphane (500microg/kg/day) or vehicle intraperitoneally for 3 days and global ischemia was performed using isolated perfused Langendorff hearts. Hearts were perfused with Krebs-bicarbonate buffer for 20min pre-ischemic period followed by a 20min global ischemia and 50min reperfusion. Treatment with sulforaphane inhibited an increase in the post-ischemic left ventricular end-diastolic pressure (LVEDP) and improved the post-ischemic left ventricular developed pressure (LVDP), +/-dP/dt, and coronary flow as compared with the untreated control hearts. Pretreatment with 5-hydroxydecanoic acid (5-HD), a mitochondrial K(ATP) channel blocker, for 10min before ischemia attenuated the improvement of LVEDP, LVDP, +/-dP/dt, and coronary flow induced by sulforaphane. Sulforaphane markedly decreased the infarcted size and attenuated the increased lactate dehydrogenase level in effluent during reperfusion. Pretreatment with 5-HD also blocked these protective effects of sulforaphane. Post-ischemia increased the concentration of atrial natriuretic peptide in coronary effluent, which attenuated by sulforaphane treatment. Decreases on Mn-superoxide dismutase (SOD), catalase, and heme oxygenase-1 levels by I/R were increased by sulforaphane treatment and pretreatment of 5-HD blocked the sulforaphane effects. Increases in Bax and caspase-3 levels, and decrease in Bcl-2 level by I/R were attenuated by sulforaphane treatment. These results suggest that the protective effects of sulforaphane against I/R injury may be partly mediated through mitochondrial K(ATP) channels and antioxidant pathway.
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PMID:Sulforaphane protects ischemic injury of hearts through antioxidant pathway and mitochondrial K(ATP) channels. 1994 20

Ca(2+)-calmodulin-dependent protein kinase II (CaMKII) plays an important role mediating apoptosis/necrosis during ischemia-reperfusion (IR). We explored the mechanisms of this deleterious effect. Langendorff perfused rat and transgenic mice hearts with CaMKII inhibition targeted to sarcoplasmic reticulum (SR-AIP) were subjected to global IR. The onset of reperfusion increased the phosphorylation of Thr(17) site of phospholamban, without changes in total protein, consistent with an increase in CaMKII activity. Instead, there was a proportional decrease in the phosphorylation of Ser2815 site of ryanodine receptors (RyR2) and the amount of RyR2 at the onset of reperfusion, i.e. the ratio Ser2815/RyR2 did not change. Inhibition of the reverse Na(+)/Ca(2+)exchanger (NCX) mode (KBR7943) diminished phospholamban phosphorylation, reduced apoptosis/necrosis and enhanced mechanical recovery. CaMKII-inhibition (KN-93), significantly decreased phospholamban phosphorylation, infarct area, lactate dehydrogenase release (LDH) (necrosis), TUNEL positive nuclei, caspase-3 activity, Bax/Bcl-2 ratio and Ca(2+)-induced mitochondrial swelling (apoptosis), and increased contractile recovery when compared with non-treated IR hearts or IR hearts pretreated with the inactive analog, KN-92. Blocking SR Ca(2+) loading and release (thapsigargin/dantrolene), mitochondrial Ca(2+) uniporter (ruthenium red/RU360), or mitochondrial permeability transition pore (cyclosporine A), significantly decreased infarct size, LDH release and apoptosis. SR-AIP hearts failed to show an increase in the phosphorylation of Thr(17) of phospholamban at the onset of reflow and exhibited a significant decrease in infarct size, apoptosis and necrosis respect to controls. The results reveal an apoptotic-necrotic pathway mediated by CaMKII-dependent phosphorylations at the SR, which involves the reverse NCX mode and the mitochondria as trigger and end effectors, respectively, of the cascade.
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PMID:The signalling pathway of CaMKII-mediated apoptosis and necrosis in the ischemia/reperfusion injury. 2006 4

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

The present study was designed to investigate the protective effects of 4-guanidino-n-butyl syringate (leonurine), a compound in Herba Leonuri (HL) on ischemic rat heart to determine the protective mechanisms associated with ischemic rat hearts. Rat heart ischemia was induced by ligation of the left coronary artery. Creatine kinase (CK) and lactate dehydrogenase (LDH) in plasma and superoxide dismutase (SOD) activity in heart homogenates were measured. We found leonurine significantly decreased levels of LDH and CK activities in plasma. This observation corresponded with decreased infarct size of ischemic rat heart induced by ligation of the left coronary artery. Moreover, the mRNA expression of the pro-apoptotic gene Bax was significantly down-regulated by 0.68-fold (p < 0.05) and the anti-apoptotic gene Bcl-2 was up-regulated by 1.41-fold (p < 0.05) in the leonurine treated groups as compared with acute myocardium ischemia (MI) controls measured by RT-PCR. Correspondingly, Bcl-2 and Bax protein levels detected by Western blotting coincided with gene expression levels. In addition, the mRNA expression level of the antioxidant enzyme Mn-SOD was significantly increased 1.23-fold (p < 0.05) and this finding corresponded with an observed increase in SOD activity and also with a committed decrease in lipid peroxidation. Taken together, our results demonstrated that leonurine attenuated myocardium injury during MI via antioxidative and anti-apoptotic effects and leonurine might become a useful adjuvant cardioprotective agent.
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PMID:Leonurine improves ischemia-induced myocardial injury through antioxidative activity. 2018 83

Premenopausal women have less cardiovascular disease and lower cardiovascular morbidity and mortality than men the same age. Our previous studies showed that female mice have lower mortality and better preserved cardiac function after myocardial infarction. However, the precise cellular and molecular mechanisms responsible for such a sex difference are not well established. Using cultured adult mouse cardiomyocytes, we tested the hypothesis that the survival advantage of females stems from activated estrogen receptors and Akt survival signaling pathways. Adult mouse cardiomyocytes were isolated from male and female C57BL/6J mice and treated with hydrogen peroxide (100 micromol/L) for 30 minutes. Cell survival was indicated by rod ratio (rod shaped cells:total cells), cell death by lactate dehydrogenase release, and positive staining of annexin-V (a marker for apoptosis) and propidium iodide (a marker for necrosis). In response to hydrogen peroxide(,) female adult mouse cardiomyocytes exhibited a higher rod ratio, lower lactate dehydrogenase release, and fewer Annexin-V-positive and propidium iodide-positive cells compared with males. Phospho-Akt was greater in females both at baseline and after hydrogen peroxide stimulation. The downstream molecule of Akt, phosphor-GSK-3beta (inactivation), was also higher, whereas caspase 3 activity was lower in females in response to hydrogen peroxide. Bcl-2 did not differ between sexes. Estrogen receptor-alpha was the dominant isoform in females, whereas estrogen receptor-beta was low but similar in both sexes. Our findings demonstrate that female adult mouse cardiomyocytes have a greater survival advantage when challenged with oxidative stress-induced cell death. This may be attributable to activation of Akt and inhibition of GSK-3beta and caspase 3 through an estrogen receptor-alpha-mediated mechanism.
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PMID:Female adult mouse cardiomyocytes are protected against oxidative stress. 2021 61

Interleukin-16 (IL-16) is a pro-inflammatory cytokine released by many types of cells found in the lungs, including normal airway and alveolar epithelial cells. Though a chemotactin for CD4(+) cells and eosinophils, IL-16 also modulates their production of factors that influence inflammatory lung diseases, e.g., asthma and allergic rhinitis. To date, little is known about any potential autocrine-like regulatory effects of IL-16. Using a model human alveolar basal epithelial A549 cell line, the present study sought to assess lung epithelial cell responses to IL-16. Potential induced effects on cell growth/function were assessed using MTT reduction, lactate dehydrogenase release, and 5-bromo-2-deoxyuridine incorporation assays. As IL-16 (at locally high levels) can induce CD4(+) cell death via apoptosis, this potential outcome among the A549 cells was also evaluated using TUNEL and changes in expression of caspase-3 and the pro-apoptotic and anti-apoptotic proteins of Bcl-2 family. The data here indicated that IL-16 inhibited A549 cell growth/function and this was associated with a marked increase in apoptosis characterized by DNA fragmentation, activation of caspase-3, and altered pro-apoptotic protein expression. Since lung epithelial cells lack the CD4 that may bind IL-16, it has been suggested that CD9 may act as an alternate receptor for this cytokine (i.e., an IL-16R). Thus, these studies also sought to determine the extent of CD9 expression on A549 cells and if any/all observed IL-16-induced changes were mediated by CD9. Flow cytometric analyses revealed the cells to be CD9(+)CD4(-). However, neutralization of the purported IL-16R with anti-CD9 antibody could not block the cytotoxic/growth inhibiting effects of IL-16. The only exception appeared to be a mitigation of a chemotactic effect of IL-16; however, studies with an equal amount of non-specific antibody (of same isotype as the anti-CD9) revealed this effect to be artefactual. The neutralization study results thus suggest to us that as-yet undefined pathway(s) exist through which IL-16 may act to exert growth inhibiting/apoptosis-inducing effects on A549 cells, a cell line routinely used as a model for lung epithelial cells.
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PMID:IL-16 effects on A549 lung epithelial cells: dependence on CD9 as an IL-16 receptor? 2030 49

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


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