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 the present study was to access the protective effect of a novel synthesized squamosamide cyclic analogue, compound FLZ, on memory impairment in artificially senescent mice induced by chronic injection of D-galactose and sodium nitrite (NaNO(2)). Artificially senescent mouse model was induced by consecutive injection of D-galactose (120 mg/kg) and NaNO(2) (90 mg/kg) once daily for 60 days. Compound FLZ (75 and 150 mg/kg) was orally administered once daily for 30 days after D-galactose and NaNO(2) injection for 30 days. The water maze test was used to evaluate the learning and memory function of mice. The content of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in serum were determined using different biochemical kits. The alterations in hippocampus morphology were assessed by light and electronic microscope. Immunoreactive cells of Bcl-2 in the hippocampus were counted by immunohistochemical staining, and Bcl-2 protein expression was analysed by Western blot method. The results indicate that injection of D-galactose and NaNO(2) induces memory impairment and neuronal damage in hippocampus of mice. In addition, serum SOD and GSH-Px activities decreased, while MDA level increased. Bcl-2-positive neurons and Bcl-2 protein expression in the hippocampus decreased remarkably. Oral administration of FLZ for 30 days significantly improved the cognitive deficits and the biochemical markers mentioned above, and also reduced the pathological alterations in mouse hippocampus. The results suggest that FLZ ameliorates memory deficits and pathological injury in artificially senescent mice induced by chronic injection of D-galactose and NaNO(2), indicating that FLZ is worth further studies for fighting antisenescence and dementia.
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PMID:A novel cyclic squamosamide analogue compound FLZ improves memory impairment in artificial senescence mice induced by chronic injection of D-galactose and NaNO2. 1797 Oct 66

The GAL1 and GAL10 genes of Saccharomyces cerevisiae are transcribed divergently and transcription of both genes can be induced by galactose and repressed by glucose. This study describes the construction and characterization of 8 bidirectional expression vectors. These vectors carry both a modified inducible GAL promoter in one direction and a constitutive GPD promoter in the reverse direction. When the gene-encoded alpha-galactosidase was cloned into the modified GAL1 and GAL10 vectors, promoter activity was 85% of wild-type for the GAL1 promoter and 90% of wild-type for the GAL10 promoter, respectively. The modified GAL promoters and GPD promoter did not interfere with one another in the bidirectional vectors. Furthermore, yeast overexpressing human Bax under the control of either modified GAL1 or modified GAL10 in a bidirectional vector conferred a lethal phenotype that was rescued by coexpression of human Bcl-2 under the control of the GPD promoter in the same vector. These eight vectors can be used to express lethal genes and screen for genes that rescue the yeast from the lethal gene product.
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PMID:Construction and characterization of bidirectional expression vectors in Saccharomyces cerevisiae. 1803 31

The present study was conducted to examine the role of hecogenin-3-O-beta-D-glucopyranosyl(1-->4)-beta-D-galactopyranoside (1), which is a triterpene saponin of Tribulus terrestris in cardiocytes during chemical hypoxia-ischaemia in vitro. Neonatal rat ventricular myocytes were isolated by collagenase digestion and treated with NaCN for 12 h. Cell apoptosis was defined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) and flow cytometry. [Ca(2+)] was measured by confocal microscopy. There was a marked increase in the expression of the anti-apoptotic protein, Bcl-2, by NaCN. This change was increased by the saponin 1. PKCepsilon protein contents were increased in the cardiocyte membrane fraction in response to NaCN. PKCepsilon activation was augmented by the saponin 1. Inhibition of PKCepsilon with inhibitory peptide prevented Bcl-2 expression. Moreover, the saponin attenuated the apoptosis in cardiocyte in response to NaCN. It is therefore suggested that the saponin 1 may play a role in cardiocyte survival via PKCepsilon and Bcl-2.
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PMID:A triterpene saponin from Tribulus terrestris attenuates apoptosis in cardiocyte via activating PKC signalling transduction pathway. 1805 79

Doxorubicin, a widely used chemotherapeutic agent, can give rise to severe cardiotoxicity by inducing cardiomyocyte apoptosis. Dracocephalum rupestre Hance, a Chinese traditional herb, has therapeutic potential for cardiovascular diseases. Naringenin-7-O-glucoside is the main active constituent of D. rupestre and there is increasing interest in its therapeutic applications. The aim of this study was to evaluate the effects of naringenin-7-O-glucoside on cardiomyocyte apoptosis induced by doxorubicin. Cell viability was detected by MTT assay. Naringenin-7-O-glucoside (10, 20, and 40 microM) significantly enhanced cardiomyocyte proliferation relative to that of doxorubicin. Furthermore, naringenin-7-O-glucoside increased the protein levels of heme oxygenase-1 (HO-1) and Bcl-2 in cardiomyocytes (as detected by Western blotting) and suppressed the mRNA expression of caspase-3 and caspase-9 (as detected by RT-PCR). These results suggest that naringenin-7-O-glucoside has protective effects against doxorubicin-induced apoptosis, effects which could underlie the use of naringenin-7-O-glucoside therapeutic agent for treating or preventing cardiomyopathy associated with doxorubicin.
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PMID:Protective effects of naringenin-7-O-glucoside on doxorubicin-induced apoptosis in H9C2 cells. 1815 51

Kaempferol-7-O-beta-D-glucoside (KG), a flavonoid glycoside, isolated from Smilax china L. rhizome, displayed marked anticancer activity on a panel of established cancer cells, of which, HeLa human cervix carcinoma cells were the most sensitive. Meanwhile, the cytotoxic effects of KG on normal human cells (HEK293 embryonic kidney cells and L-02 embryonic liver cells) were much smaller than on cancer cells. This work studied the molecular mechanisms underlying KG induced growth inhibition in HeLa cells. The results showed that KG induced G2/M phase growth arrest correlated with Cyclin B1 and Cdk1 decrease in a p53-independent manner, and also caused an increase in apoptosis, which was confirmed by characteristic morphological changes, evident DNA fragmentation, increased apoptotic sub-G1 population. Furthermore, inhibition of NF-kappaB nuclear translocation, up-regulation of Bax and down-regulation of Bcl-2, were observed in HeLa cells treated with KG, which indicated that the mitochondrial pathway was involved in the apoptosis signal pathway. In summary, KG displayed a significant anti-tumor effect through cell cycle arrest and apoptotic induction in HeLa cells, which suggested that KG might have therapeutic potential against cervix carcinoma.
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PMID:Kaempferol-7-O-beta-D-glucoside (KG) isolated from Smilax china L. rhizome induces G2/M phase arrest and apoptosis on HeLa cells in a p53-independent manner. 1834 26

Development of effective agents for treatment of hormone-refractory prostate cancer (HRPC) has become a national medical priority. D-Allose is a monosaccharide (C-3 epimer of glucose) distributed rarely in nature; because of its scarcity and cost, the biological effect has hardly been studied. In the present study, we demonstrated the inhibitory action of D-allose on proliferation of human HRPC cell lines, DU145 and PC-3 in a dose- and time-dependent manner, while human normal prostate epithelial (NPE) cell line, PrEC showed no remarkable effect. In vitro treatment of D-allose resulted in the alteration of Bcl-2/Bax ratio in favor of apoptosis (programmed cell death, PCD) in both the HRPC cell lines, which was associated with the lowering of mitochondrial transmembrane potential (Deltapsi(m)) and the release of cytochrome C (cyt C), the cleavage of caspase 3 and poly (ADP-ribose) polymerase (PARP), and the elevation of calcium concentration in cytosol ([Ca(2+)](c)). D-Allose also induced G1 phase arrest of the cell cycle in DU145 cell line. This study for the first time suggested the antiproliferative effect of D-allose through induction of PCD in HRPC cell lines, which could be due to the modulation of mitochondria mediated intrinsic apoptotic pathway.
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PMID:Rare sugar D-allose induces programmed cell death in hormone refractory prostate cancer cells. 1862 5

Polygonatum cyrtonema lectin (PCL), a mannose/sialic acid-binding lectin, has been reported to display remarkable inhibitory and cytotoxic activity toward cancer cells. However, the precise mechanism by which PCL induces tumor cell death is still only rudimentarily understood. In the present study, PCL was shown to markedly inhibit the growth of human melanoma A375 cells with concomitant low toxicity to the normal melanocytes. Subsequently, PCL was found to simultaneously induce A375 cell apoptosis and autophagy. The mechanism of apoptosis following treatment with PCL involved regulation of Bax, Bcl-x(L) and Bcl-2 proteins, which then caused collapse of the mitochondrial membrane potential, leading to cytochrome c release and caspase activation. The treatment with PCL also abrogated the glutathione antioxidant system, and induced mitochondria to generate massive ROS accumulation, which subsequently resulted in p38 and p53 activation. Further experimental data confirmed that the ROS-p38-p53 pathway could be involved in the stimulation of autophagy, suggesting that autophagy may play a death-promoting role via the above-mentioned apoptotic pathway. In conclusion, these findings indicate that PCL induces both apoptosis and autophagy in cancer cells through a mitochondria-mediated ROS-p38-p53 pathway.
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PMID:Molecular mechanisms of Polygonatum cyrtonema lectin-induced apoptosis and autophagy in cancer cells. 1913 34

Concanavalin A (Con A) is known to induce acute hepatitis that is mediated by activation of NKT and T-cell and cytokine production in immunocompetent mice. The observation of Con A-induced autophagic cell death of hepatoma cells via a Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 mediated autophagic pathway made us re-evaluate the effect of Con A-induced hepatitis in mice. Con A was administrated intravenously to BABL/c, SCID, or SCID/NOD mice at doses of 20, 30 or 40 mg/kg, respectively, to induce acute hepatitis. The levels of hepatitis and autophagy induction were both analyzed. We found that Con A can induce acute hepatitis in SCID or SCID/NOD mice with kinetics similar to that of BALB/c, but requiring a higher dose of Con A. No lymphocyte infiltrations were found in SCID or SCID/NOD mice, and the cytokine productions were different. An autophagy with microtubule-associated protein light chain 3-II conversion was demonstrated in the liver post-Con A injection in SCID/NOD mice. Due to the mannose/glucose-specific binding on cell membrane, Con A can induce a T-cell-independent acute hepatitis with autophagy in SCID/NOD mice.
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PMID:Autophagy induction in T cell-independent acute hepatitis induced by concanavalin A in SCID/NOD mice. 1914 67

Many natural polyphenolic compounds have been shown to attenuate reactive oxygen/nitrogen species (ROS/RNS) formation and protect against ischemia/reperfusion injury both in vitro and in vivo. 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside (TSG), an active component of the rhizome extract from Polygonum multiflorum, exhibits antioxidative and anti-inflammatory effects. Here, we used an in vitro ischemic model of oxygen-glucose deprivation followed by reperfusion (OGD-R) and an in vivo ischemic model of middle cerebral artery occlusion (MCAO) to investigate the neuroprotective effects of TSG on ischemia/reperfusion brain injury and the related mechanisms. We demonstrated that OGD-R-induced neuronal injury, intracellular ROS generation, and mitochondrial membrane potential dissipation were reversed by TSG. The elevation of H2O2-induced [Ca2+]i was also attenuated by TSG. Inhibition of the c-Jun N-terminal kinase (JNK) and Bcl-2 family-related apoptotic signaling pathway was involved in the neuroprotection afforded by TSG. Meanwhile, TSG inhibited iNOS mRNA expression induced by OGD-R, which may be mediated by the activation of SIRT1 and inhibition of NF-kappaB activation. In vivo studies further demonstrated that TSG significantly reduced the brain infarct volume and the number of positive cells by TUNEL staining in the cerebral cortex compared to the MCAO group. Our study indicates that TSG protects against cerebral ischemia/reperfusion injury through multifunctional cytoprotective pathways.
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PMID:Protection by tetrahydroxystilbene glucoside against cerebral ischemia: involvement of JNK, SIRT1, and NF-kappaB pathways and inhibition of intracellular ROS/RNS generation. 1927 42

The objectives of this study were to determine the antiproliferation effect of prostate cancer cell lines LNCaP and PC-3 as affected by 4 isoflavone fractions prepared from soybean cake and isoflavone standards genistein and daidzein. With the MTT test, most treatments were effective in inhibiting prostate cancer cell growth at a low dose of 5 and 10 mug/mL. In cell cycle analysis, the fractions of aglycon, a mixture of acetylglucoside and aglycon, as well as genistein and a combination of genistein and daidzein standards exhibited a high G2/M ratio for LNCaP, as did the acetylglucoside, genistein and a combination of genistein and daidzein standards for PC-3. Results of Western blotting revealed an increase in p53 protein expression of LNCaP following treatments of the aglycon fraction, genistein and a combination of genistein and daidzein standards. However, all the treatments did not affect Bcl-2 protein expression significantly in both LNCaP and PC-3 cells. A decline in cyclin B1 expression of LNCaP was observed for all the treatments, with the mixture of acetylglucoside and aglycon possessing the most pronounced effect. But for PC-3, a decrease in cyclin B1 expression was shown for all the isoflavones, with the exception of malonylglucoside, glucoside and acetylglucoside fractions. The outcome of this study may provide a basis for possible production of functional food in the future with soybean cake as raw material.
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PMID:Antiproliferation effect and mechanism of prostate cancer cell lines as affected by isoflavones from soybean cake. 1929 64


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