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

We previously showed that C-phycocyanin (PC), an antioxidant biliprotein pigment of Spirulina platensis (a blue-green alga), effectively inhibited doxorubicin-induced oxidative stress and apoptosis in cardiomyocytes. Here we investigated the cardioprotective effect of PC against ischemia-reperfusion (I/R)-induced myocardial injury in an isolated perfused Langendorff heart model. Rat hearts were subjected to 30 min of global ischemia at 37 degrees C followed by 45 min of reperfusion. Hearts were perfused with PC (10 microM) or Spirulina preparation (SP, 50 mg/l) for 15 min before the onset of ischemia and throughout reperfusion. After 45 min of reperfusion, untreated (control) hearts showed a significant decrease in recovery of coronary flow (44%), left ventricular developed pressure (21%), and rate-pressure product (24%), an increase in release of lactate dehydrogenase and creatine kinase in coronary effluent, significant myocardial infarction (44% of risk area), and TdT-mediated dUTP nick end label-positive apoptotic cells compared with the preischemic state. PC or SP significantly enhanced recovery of heart function and decreased infarct size, attenuated lactate dehydrogenase and creatine kinase release, and suppressed I/R-induced free radical generation. PC reversed I/R-induced activation of p38 MAPK, Bax, and caspase-3, suppression of Bcl-2, and increase in TdT-mediated dUTP nick end label-positive apoptotic cells. However, I/R also induced activation of ERK1/2, which was enhanced by PC treatment. Overall, these results for the first time showed that PC attenuated I/R-induced cardiac dysfunction through its antioxidant and antiapoptotic actions and modulation of p38 MAPK and ERK1/2.
 ...
PMID:C-phycocyanin protects against ischemia-reperfusion injury of heart through involvement of p38 MAPK and ERK signaling. 1637 83

Oxidative stress has a complex effect on cancer development. To further study this process, we induced colon tumors with azoxymethane (AOM) in mice deficient for uncoupling protein-2 (UCP2). UCP2 has recently emerged as a negative regulator of mitochondrial oxidant production. When overexpressed, UCP2 protects cells from oxidative stress, while its absence may cause abundance of reactive oxygen species, release of pro-inflammatory cytokines and persistent activation of nuclear factor kappaB (NF-kappaB), a pleiotropic transcription factor with an increasingly recognized role in cancer. Here we show that Ucp2-/- mice develop more aberrant crypt foci and colon tumors than Ucp2+/+ littermates when examined 24 weeks after the completion of treatment with AOM (10 mg/kg i.p. weekly for a total of 6 weeks, n = 8-12). This effect is primarily seen in the proximal colon of Ucp2-/- mice (P < 0.05), in association with changes indicative of increased oxidative stress (increased staining for malondialdehyde and inducible nitric oxide synthase), enhanced NF-kappaB activation (increased levels of phosphorylated IkappaB and increased nuclear presence of p65) and a disrupted balance between intestinal epithelial cell proliferation (greater 5-bromo-2'-deoxy-uridine incorporation rates and increased phosphorylation of ERK1/2 and AKT) and apoptosis (decreased number of terminal deoxynucleotidyltransferase-mediated nick-end-labeling (TUNEL)-positive cells and increased expression of Bcl-2). In conclusion, our findings provide the first in vivo evidence for a link between UCP2 and tumorigenesis and indicate the need for additional studies to assess the role of mitochondrial uncoupling in cancer development.
 ...
PMID:Enhanced colon tumor induction in uncoupling protein-2 deficient mice is associated with NF-kappaB activation and oxidative stress. 1640 37

The in vivo effects of melatonin on proliferation and apoptosis of 17-beta-estradiol (E2)-induced pituitary prolactin-secreting tumor (prolactinoma) were investigated in rats kept in 12 L/12 D (lights on: 06:00-18:00 hr). As melatonin was shown to induce apoptosis of breast and liver tumor cells, we examined whether melatonin would induce apoptosis of rat pituitary prolactinoma cells. 0.125, 0.25, 0.50 or 1.0 mg melatonin/day/rat was administrated subcutaneously at 17:30-18:00 hr. The weight of prolactinomas was measured. Apoptosis was evaluated using the TdT-mediated dUTP nick-end labeling method. It was found that treatment with 0.25 and 0.50 mg melatonin for 97 days inhibited prolactinoma cell proliferation and increased prolactinoma cell apoptosis. Furthermore, melatonin induced mRNA expression of Bax and cytochrome c protein expression. Conversely, mRNA expression of Bcl-2, and mitochondrial membrane potential were inhibited by melatonin treatment. These results suggest that melatonin inhibits the proliferation and induces apoptosis of rat pituitary prolactin-secreting tumor via perturbation of mitochondria physiology.
 ...
PMID:Inhibitory effects of melatonin on the growth of pituitary prolactin-secreting tumor in rats. 1649 59

The aim of the present investigation was to evaluate the effect of an extract from Corydalis yanhusuo W.T., a Chinese herbal medicine, on ischemia/reperfusion (I/R) injury and to determine the mechanism(s) involved. In rats, the left anterior descending (LAD) coronary artery was occluded for 30 min and then reperfused for 6 h. 0.5% carboxymethyl cellulose sodium was used as a vehicle (I/R control group) and Corydalis yanhusuo rhizoma extract (I/R + CY 200, 100 mg/kg groups) were given. Infarct size and hemodynamic parameters were measured. Apoptosis was detected quantitatively by the terminal transferase dUTP nick end-labeling (TUNEL) method and confirmed by DNA laddering on agarose gel. The expression of anti-apoptotic Bcl-2 and pro-apoptotic Bax proteins was visualized by western blot analysis. In contrast to the I/R control group, administration with CY 200 mg/kg resulted in a significant reduction in the infarct size and an improvement in heart function as evidenced by higher LVSP and +/-dp/dtmax. TUNEL-positive cells in the ischemic myocardium were also significantly reduced in the I/R + CY 200, 100 mg/kg groups, consistent with little DNA laddering in these two groups. Furthermore, greater Bcl-2 and attenuated Bax expression was found in the CY treated rats. These results suggest that the protective effect of Corydalis yanhusuo on myocardial I/R injury is closely associated with the inhibition of myocardial apoptosis through modulation of the Bcl-2 family.
 ...
PMID:Corydalis yanhusuo rhizoma extract reduces infarct size and improves heart function during myocardial ischemia/reperfusion by inhibiting apoptosis in rats. 1661 56

Cloned animals developed from somatic cell nuclear transfer (SCNT) embryos are useful resources for agricultural and medical applications. However, the birth rate in the cloned animals is very low, and the cloned animals that have survived show various developmental defects. In this report, we present the morphology and differentially regulated proteins in the extraembryonic tissue from SCNT embryos to understand the molecular nature of the tissue. We examined 26-day-old SCNT porcine embryos at which the sonogram can first detect pregnancy. The extraembryonic tissue from SCNT embryos was abnormally small compared with the control. In the proteomic analysis with the SCNT extraembryonic tissue, 39 proteins were identified as differentially regulated proteins. Among up-regulated proteins, Annexins and Hsp27 were found. They are closely related to the processes of apoptosis. Among down-regulated proteins, Peroxiredoxins and anaerobic glycolytic enzymes were identified. In the Western blot analysis, antioxidant enzymes and the antiapoptotic Bcl-2 protein were down-regulated, and caspases were up-regulated. In the terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) assay with the placenta from SCNT embryos, apoptotic trophoblasts were observed. These results demonstrate that a major reason for the low birth rate of cloned animals is due to abnormal apoptosis in the extraembryonic tissue during early pregnancy.
 ...
PMID:Proteomic analysis of the extraembryonic tissue from cloned porcine embryos. 1681 48

Effects of adenoviral therapy and reduced apoptosis on immune response were investigated in a rat liver transplantation model after prolonged ischemia-reperfusion. Liver donors were treated i.v. either with an adenoviral construct, expressing bcl-2, green-fluorescent-protein, or doxycyclin. Intrahepatic apoptosis was assessed by terminal transferase dUTP nick end labeling assay. The intrahepatic presence of CD4, CD8a, CD163, immunoglobulin (Ig)beta, tumor necrosis factor (TNF)-alpha and myeloperoxidase (MPO) was quantified by realtime polymerase chain reaction at 24 hours and seven days after transplantation. Bcl-2 expression abrogated the TNF-alpha elevation and reduced apoptosis of hepatocytes and sinusoidal endothelial cells as compared to advCMV green fluorescent protein. No effects on CD4, CD8a, CD163 and MPO expression were noticed in bcl-2 pretreated livers, whereas Igbeta was slightly enhanced compared to controls. Adenoviral infected liver grafts trigger an immune response but reduced apoptosis resulted in down-regulation of TNF-alpha. Thus, bcl-2 transfer might simultaneously reduce graft ischemia reperfusion injury and immunogenicity.
 ...
PMID:Inhibition of apoptosis reduces immunogeneic potential of adenoviral-treated syngeneic liver grafts. 1713 Jul 89

This study aims to investigate the role of granzyme B in the apoptosis of nasal-type NK/T-cell lymphoma. Twenty-four nasal-type NK/T-cell lymphomas were examined by TdT-mediated deoxyuridine triphosphate (dUTP)-biotin nick-end labeling (TUNEL) assay and immunohistochemical staining for active caspase 3, poly(ADP-ribose) polymerase (PARP-1/p85)/p85, and Bcl-2. In addition, HANK-1 and NKL cell lines were analyzed using Western blot analysis. Immunoprecipitation was performed to identify the binding of granzyme B and intrinsic serpin proteinase inhibitor 9 (PI-9). To localize granzyme B, immunogold labeling and immunofluorescence staining were performed. The expression level of granzyme B in tumor tissue was correlated with the apoptosis rate (P=0.015), degree of necrosis (P=0.002), and the levels of active caspase 3 (P=0.036) and poly ADP-ribose polymerase (PARP)-1/p85 (P=0.040). The granzyme B-positive HANK-1 cell line showed increased spontaneous cell death compared to the granzyme B-negative NKL cell line. The untreated HANK-1 cells released cytochrome c into the cytosol with cleavage of caspase 3 and PARP-1. Treatment with granzyme B inhibitor and caspase inhibitor decreased the cleavage of PARP-1. By performing immunogold labeling, granzyme B was identified within the cytolytic granules as well as in the cytosol. Confocal microscopy and immunoprecipitation assays confirmed the colocalization of PI-9 and granzyme B, which formed an SDS-resistant complex. These results suggested that granzyme B leakage induces cell death in NK/T-cell lymphomas via both caspase-dependent and -independent mechanisms, and this leads to the extensive necrosis that is commonly seen in NK/T-cell lymphoma.
 ...
PMID:Granzyme B leakage-induced apoptosis is a crucial mechanism of cell death in nasal-type NK/T-cell lymphoma. 1726 2

The cellular stress response can mediate cellular protection through expression of heat shock protein (Hsp70), which can interfere with the process of apoptotic cell death. Factors regulating renal epithelial cell apoptosis include angiotensin II. In the present study, we have examined the relationship between the Hsp70 expression and the apoptotic pathway in the kidneys from low-protein-fed rats (8% protein). The possible cytoprotective role of Hsp70 has been evaluated during low-protein feeding and after reincorporation of 24% protein in the diet. The effect of angiotensin II AT1 receptor inhibition has also been studied. Rats were fed with a low-protein (LP) diet (8% protein) for 14 days, and then the animals were recovered by means of a normal protein diet (24% protein) (RP) for 14, 21, and 30 days, and control rats received 24% protein (NP) in the diet. LP and NP rats treated with Losartan (10 mg/kg) were also evaluated. The following methods were performed on the kidneys: terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling assay for apoptosis, reverse transcriptase-polymerase chain reaction assay for AT1, Bax, and Bcl-2 messenger ribonucleic acid (mRNA) expression, and immunohistochemical and Western blot for Hsp70 and caspase 3 protein expression and activity. In the LP group, the cells of the medullary ducts (MDs) showed increased apoptosis associated with weak immunoreaction for Hsp70 and decreased Hsp70 protein levels. In these animals, enhanced proapoptotic ratio Bax/Bcl-2 linked to decreased procaspase 3 protein levels with increased caspase 3 activation were demonstrated. A cytoprotection attributed to Hsp70 could be noted in the RP rats after 21 days of reincorporation of the normal diet, and in the LP-fed group treated with Losartan. In these cases, the MD cells displayed decreased apoptosis and increased Hsp70 expression in colocalization staining, and high Hsp70 levels in cytosolic fraction. A decreased proapoptotic ratio Bax/Bcl-2, associated with increased Bcl-2 mRNA, was also observed. Our results provide evidence for an antiapoptotic, cytoprotective effect of Hsp70 in kidney MD cells of rats with LP intake, when the animals were recovered with 24% protein in diet and after angiotensin II AT1 receptor inhibition. Angiotensin II seems to play a role in the pathogenesis of tubule epithelial cell apoptosis during LP feeding.
 ...
PMID:Heat shock protein 70 expression is associated with inhibition of renal tubule epithelial cell apoptosis during recovery from low-protein feeding. 1727 80

Earlier studies showed that melatonin reduced the growth of 17-beta-estradiol (E(2))-induced rat pituitary prolactin-secreting tumor (prolactinoma) in vivo. The mechanisms of melatonin's inhibitory action on the prolactin-secreting tumor were further explored by investigating the in vitro effects of melatonin on the growth of pituitary prolactin-secreting tumor cells. Primary cultured prolactinoma cells from E(2)-induced rat pituitary prolactin-secreting tumor were treated with 10(-5), 10(-4) or 10(-3) m melatonin for 5 days. Apoptosis was evaluated using flow cytometry and the TdT-mediated dUTP nick-end labeling (TUNEL) method. In addition, cell viability was analyzed by (3,4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. It was found that incubation of prolactinoma cells with 10(-5), 10(-4) or 10(-3) m melatonin for 5 days inhibited cell growth and increased cell apoptosis. Furthermore, melatonin increased caspase-3 activity, Bax mRNA expression, and cytochrome c protein expression. Conversely, Bcl-2 mRNA expression and mitochondrial membrane potential were inhibited by melatonin treatment. Our results further suggest that melatonin inhibits tumor growth by inducing apoptosis of rat pituitary prolactin-secreting tumor directly via the damage of mitochondria.
 ...
PMID:Antiproliferative effects of melatonin on the growth of rat pituitary prolactin-secreting tumor cells in vitro. 1728 50

Two groups of rats were used to examine the effect of pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARgamma) agonist, on rat hearts using an in vivo model of ischemia-reperfusion (I/R) to elucidate potential mechanisms. One group was the 30-min reperfusion group, which was further subdivided into sham (n=5), vehicle (n=6) and pioglitazone (3 mg x kg(-1), n=7) treatment groups with 30 min ischemia followed by 30 min reperfusion to detect data related to cardiac function and the area of myocardial infarction. The other group was the 120-min reperfusion group, subdivided into sham (n=5), vehicle (n=6), and pioglitazone 0.3 mg x kg(-1) (n=6), 1 mg x kg(-1) (n=7) and 3 mg x kg(-1) (n=6) treatment groups. Immunohistochemistry, in situ hybridization, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) and DNA agarose gel electrophoresis were performed to detect apoptosis and expressions of Bax, Bcl-2, caspase 3, MMP-2 and PPARgamma protein, and MMP-2 and PPARgamma mRNA. We found that, after acute treatment with pioglitazone, the ratio of necrosis to area at risk decreased by 28% (p<0.01) and that of necrosis to left ventricle was reduced by 32% (p<0.01), compared with the vehicle group. Heart rate and +dp/dt(max), representing the cardiac systolic function, as well as -dp/dt(max), the indicator of cardiac diastolic function, improved significantly at 1 and 30 min after reperfusion (p<0.05-0.01). Furthermore, myocardial apoptosis was significantly suppressed by acute treatment with pioglitazone as evidenced by the decreased number of TUNEL-positive myocytes and DNA ladder, enhanced Bcl-2 protein expression, reduced Bax and caspase 3 protein expression in a dose-dependent manner compared with vehicle-treated rats. In addition, acute treatment with pioglitazone dose-dependently increased PPARgamma expression and decreased MMP-2 expression at protein and mRNA levels. Our findings demonstrate that a PPARgamma agonist may protect the heart from I/R injury. The protective effect is likely to occur by reducing cardiomyocyte apoptosis and inhibiting MMP-2.
 ...
PMID:Effect of pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, on ischemia-reperfusion injury in rats. 1735 10


<< Previous 1 2 3 4 5 6 7 8 9 10