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)

Sarcopenia is characterized by increased regenerating myofibres and decreased myofibre size. Sarcopenia progression might be partially regulated by ageing-related signals associated with necrotic fibre disruption and nuclear apoptosis. This study sought to identify ageing-related signals in aged atrophying skeletal muscle by comparison with unloaded muscle atrophy in adults. Adult (6-month) and old (32-month) rats were used. Some adult rats were subjected to 2 weeks of hindlimb unloading (6-month-HU). Histological analysis found that regenerating fibres increased by about 30-fold only in 32-month aged soleus muscle compared with 6-month rats. The number of apoptotic DNA fragmented nuclei was increased by 3.9-fold in 6-month-HU and 2.8-fold in 32-month rats. Cleaved caspase-3 was observed at high levels on basal membranes and in nuclei in 32-month rats. By Western blot analysis additional ageing-related signals could be identified since (1) phosphorylated Bcl-2 content was increased in both cytosolic and mitochondrial fractions; (2) ER stress signal proteins caspase-12, CHOP/GADD153, and GRP78 were increased; and (3) stress-inducible chaperone HSP70 was decreased in soleus muscle from 32-month but not changed in 6-month-HU rats. We conclude that activation of ageing-related signals may mediate necrotic myofibre disruption and nuclear apoptosis induction that contribute to progression of sarcopenia.
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PMID:Differential cell death regulation between adult-unloaded and aged rat soleus muscle. 1942 51

We explored the effects and mechanisms of Rhodiola rosea extract supplementation on swimming-induced fatigue in rats. The concentrations of active components in Rhodiola rosea have been determined by high performance liquid chromatography-mass spectrometer. The Rhodiola rosea extract supplementation in water for 2-4 weeks was evaluated in male Wistar rats with 90-min unloaded swimming exercise and 5% body weight loaded swimming up to fatigue. We measured the fatigue biomarkers, including blood urea nitrogen (BUN), glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT), lactate dehydrogenase (LDH), hepatic glycogen content, the activity of fat metabolism enzymes, sterol regulatory element-binding protein-1 (SREBP-1) and fatty acid synthase (FAS), the tissue oxygen content and ratio of red and white skeletal muscle fibers in rats. Rhodiola rosea significantly increased liver glycogen, SREBP-1, FAS, heat shock protein 70 expression, Bcl-2/Bax ratio and oxygen content before swimming. Rhodiola rosea supplementation significantly increased the swimming time in a dose-dependent manner and reduced swimming-enhanced serum BUN, GOT and GPT levels. The ratio of red and white muscle fibers was not altered after chronic Rhodiola rosea extract supplementation. Chronic Rhodiola rosea supplementation significantly improved exhaustive swimming-induced fatigue by the increased glycogen content, energy supply of lipogenic enzyme expressions and protective defense mechanisms.
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PMID:Chronic Rhodiola rosea extract supplementation enforces exhaustive swimming tolerance. 1960 15

Cancer progression is associated with reduced apoptosis and increased proliferation. We hypothesized that upregulation of the Bag family of survival cochaperones and its molecular partners of the Bcl-2 and heat shock protein (HSP) families would correlate with disease progression and survival in ovarian cancer. Bag-1, Bag-4, HSP27, HSP70, Bcl-2, and Bcl-X(L) expression was immunohistochemically analyzed in effusions (188) and patient-matched solid tumors (43 primary carcinomas, 81 solid metastases). Results were analyzed for anatomic site-related differences, and association with clinicopathologic parameters and survival. Bag-1, Bag-4, and HSP70 were detected in the tumor cell nuclei and cytoplasm, whereas HSP27, Bcl-2, and Bcl-X(L) had exclusively cytoplasmic localization. Antiapoptotic protein expression in effusions differed significantly from primary tumors and metastases. Cytoplasmic Bag-1 (P=0.002), nuclear and cytoplasmic HSP70 (P<0.001), and Bcl-2 (P=0.001) expression was higher in primary carcinomas and solid metastases compared with effusions, whereas Bcl-X(L) (P=0.01), nuclear Bag-1 (P<0.001), nuclear Bag-4 (P=0.01), and cytoplasmic Bag-4 (P=0.002) were upregulated in effusions. Bcl-X(L) expression was associated with poor response to chemotherapy at diagnosis (P=0.02) and HSP27 expression was associated with high-grade tumors (P=0.01). Increased cytoplasmic HSP70 staining in effusions correlated with poor overall survival for the entire cohort (P=0.01). In primary carcinomas, higher Bcl-2 expression correlated with worse overall (P=0.04) and progression-free (P=0.02) survival. Antiapoptotic proteins are differentially expressed in effusions compared with solid tumors, whereas primary carcinomas and solid metastases have comparable expression patterns. HSP70 expression in effusions may be a prognostic marker of poor survival, with a similar role for Bcl-2 in primary carcinomas.
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PMID:Expression and clinical role of antiapoptotic proteins of the bag, heat shock, and Bcl-2 families in effusions, primary tumors, and solid metastases in ovarian carcinoma. 1962 Sep 38

To assess the dependence on age of the expression of apoptosis regulatory proteins in the human semitendinosus muscle, we measured the expression levels of several apoptosis-related genes, including apoptosis-inducing factor (AIF), Bax, Bcl-2, caspase-3 and heat shock protein 70 (HSP70), using RT-PCR, immunohistochemistry and TUNEL assays. We found that the DNA fragmentation was proportional to the age of the tissues sample donors. The expression levels of AIF were significantly elevated (by 10 to 25%) in semitendinosus tissue samples from older individuals, but the Bax, Bcl-2, caspase-3 and HSP 70 levels remained almost constant. This data suggests that the morphological and functional changes observed in aged human semitendinosus muscle correlates with the apoptosis of muscle cells through the induction of AIF.
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PMID:The age-dependent induction of apoptosis-inducing factor (AIF) in the human semitendinosus skeletal muscle. 1968 11

The Bcl-2-associated athanogene, BAG, protein family through their BAG domain associates with the heat shock protein 70 (HSP-70) and modulates its chaperone activity. One member of this family, BAG3, appears to play an important role in protein homeostasis, as its expression promotes cell survival. Expression of BAG3 is enhanced by a variety of stress-inducing agents. Here we describe a role for BAG3 to modulate transcription of its own promoter through a positive feedback loop involving its 5'-UTR sequence. Activation of the BAG3 promoter is mediated by the BAG domain and is independent of BAG3 association with the UTR sequence. Autoactivation of the BAG3 gene is observed in several cultures of human glial cells including gliomas, but not in several other non-glial cell lines such as He La and others. Results from cell fractionation and immunocytochemistry showed BAG3 in the cytoplasm as well as the nuclei of glial cells. These observations suggest that BAG3 gene expression is controlled by its own product and that this may be critical for the biological activity of BAG3 in some cell types.
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PMID:Autoregulation of co-chaperone BAG3 gene transcription. 1977 43

Cooking-oil-fumes containing toxic components may induce reactive oxygen species (ROS) to oxidize macromolecules and lead to acute lung injury. Our previous study showed that a decaffineated green tea extract containing (+)-catechin, (-)-epicatechin, (+)-gallocatechin, (-)-epigallocatechin, (-)-epicatechin gallate, and (-)-epigallocatechin gallate can inhibit oxidation, inflammation, and apoptosis. We determined whether the catechins supplement may reduce cooking-oil-fumes-induced acute lung injury in rat. In the urethane-anesthetized Wistar rat subjected to 30-120 min of cooking-oil-fumes exposure, blood ROS significantly increased in the recovery stage. After 30-min cooking-oil-fumes exposure, the enhanced blood ROS level further increased in a time-dependent manner during the recovery stage (321 +/- 69 counts/10 s after 1 h, 540 +/- 89 counts/10 s after 2 h, and 873 +/- 112 counts/10 s after 4 h). Four hours after 30-min cooking-oil-fumes exposure, lung lavage neutrophils and ROS as well as lung tissue dityrosine and 4-hydroxy-2-nonenal increased significantly. Two weeks of catechins supplememnt significantly reduced the enhanced lavage ROS, lung dityrosine and 4-hydroxy-2-nonenal level. Cooking-oil-fumes-induced oxidative stress decreased lung Bcl-2/Bax ratio and HSP70 expression, but catechins treatment preserved the downregulation of Bcl-2/Bax ratio and HSP70 expression. We conclude that catechins supplement attenuates cooking-oil-fumes-induced acute lung injury via the preservation of oil-smoke induced downregulation of antioxidant, antiapoptosis, and chaperone protein expression.
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PMID:Supplementary catechins attenuate cooking-oil-fumes-induced oxidative stress in rat lung. 1977 1

The concentrations of soluble beta-amyloid (Abeta) oligomers paralleled with the extent of synaptic loss and severity of cognitive impairment in Alzheimer patients. However, the neurotoxicity of the naturally generated Abeta species remains unknown. This study was designed to examine the effects of naturally generated Abeta oligomers, secreted from amyloid precursor protein-expressing cells, on the homeostasis and viability of primary hippocampal neurons. Our results showed that primary hippocampal neurons incubated with condition media containing cell-secreted soluble Abeta had higher levels of heat-shock protein (HSP)27, HSP60 and HSP70, and lower levels of HSP32 than those of the control neurons. The cell-secreted soluble Abeta caused mitochondria dysfunction in hippocampal neurons as demonstrated by depolarized membrane potential and decreased cytochrome c oxidase activity and ATP levels. The levels of pro-apoptotic proteins, Bid, Bax and cytochrome C, were elevated; whereas anti-apoptotic Bcl-2 protein was reduced in the soluble Abeta-cultured neurons. Apoptosis was also evident in these soluble Abeta-cultured neurons. These results indicate that naturally secreted Abeta induces neuronal injury/death by activating an apoptotic pathway involving impaired mitochondria function and cellular homeostasis.
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PMID:Cell-derived soluble oligomers of human amyloid-beta peptides disturb cellular homeostasis and induce apoptosis in primary hippocampal neurons. 1980 65

A complex of human alpha-lactalbumin and oleic acid (HAMLET) was originally isolated from human milk as a potent anticancer agent. It kills a wide range of transformed cells of various origins while leaving nontransformed healthy cells largely unaffected both in vitro and in vivo. Importantly, purified alpha-lactalbumins from other mammals form complexes with oleic acid that show biological activities similar to that of HAMLET. The mechanism by which these protein-lipid complexes kill tumor cells is, however, largely unknown. Here, we show that complex of bovine alpha-lactalbumin and oleic acid (BAMLET), the bovine counterpart of HAMLET, kills tumor cells via a mechanism involving lysosomal membrane permeabilization. BAMLET shows potent cytotoxic activity against eight cancer cell lines tested, whereas nontransformed NIH-3T3 murine embryonic fibroblasts are relatively resistant. BAMLET accumulates rapidly and specifically in the endolysosomal compartment of tumor cells and induces an early leakage of lysosomal cathepsins into the cytosol followed by the activation of the proapoptotic protein Bax. Ectopic expression of three proteins known to stabilize the lysosomal compartment, i.e. heat shock protein 70 (Hsp70), Hsp70-2, and lens epithelium-derived growth factor, confer significant protection against BAMLET-induced cell death, whereas the antiapoptotic protein Bcl-2, caspase inhibition, and autophagy inhibition fail to do so. These data indicate that BAMLET triggers lysosomal cell death pathway in cancer cells, thereby clarifying the ability of alpha-lactalbumin:oleate complexes to kill highly apoptosis-resistant tumor cells.
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PMID:BAMLET activates a lysosomal cell death program in cancer cells. 2005 71

Spontaneous leiomyomas of the oviduct are common tumors of the Japanese quail (Coturnix coturnix japonica) and laying hens. This makes it a good animal model for screening potential agents for testing in the prevention and treatment of human myoma uteri. Genistein has been shown to inhibit the growth of various cancer cells. We investigated the effects of genistein supplementation on the development of fibroid tumors in the oviduct, serum oxidative stress markers [malondialdehyde (MDA), 8-isoprostane, 4-hydroxyalkenal (HAE), 8-hydroxy-2' -deoxyguanosine (8-OHdG) levels], soy isoflavone levels, and tissue biomarkers [Connexin 43 (Cx43), Bcl-2, and Bax and heat shock protein 70 (Hsp70) expression] in Japanese quail. One hundred and fifty quail (12 mo old) were assigned to 3 experimental groups as 5 replicates of pens containing 10 birds in each. Birds were fed either a basal diet or the basal diet supplemented with 400 mg or 800 mg of genistein/kg of diet. The animals were sacrificed after 315 days, and the tumors were identified. Genistein supplementation significantly decreased the incidence of fibroid tumors as compared to control birds (P = 0.04). The tumors in genistein-fed birds were smaller than those found in control birds (P = 0.02). Serum MDA, 8-isoprostane, and HAE levels were lower in treatment groups than in control group (MDA: 2.01 vs. 0.82; 8-isoprostane: 135 vs. 101; HAE: 1.45 vs. 0.73; P <or= 0.01). The concentrations of serum 8-OHdG, which is a marker of oxidative damage, in the groups were 27.5, 22.4, and 21.3 ng/ml, respectively (P = 0.05). The expression of cell cycle regulatory proteins, Bcl-2, was 4.18 and 4.61 in the genistein groups and 6.21 in the control group, and the expression of Bax was 10.93 and 16.78 in the genistein groups and 7.60 in the control group (P < 0.001 for Bax). Cx43 level was 2.56 and 2.40 in the genistein groups compared with 5.15 in the control group. None of the differences in the Cx43 and Bcl-2 of the groups were significant. The expression of heat shock proteins, Hsp60 and Hsp70, were not different between groups, although Hsp70 level of the genistein groups (19.73) was lower than the control group (27.8). The results indicate that dietary supplementation of genistein reduces the incidence and size of spontaneously occurring leiomyoma of the oviduct in the Japanese quail. Clinical trials should be conducted to investigate the efficacy of genistein supplementation in the prevention and treatment of uterine leiomyoma in humans.
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PMID:Genistein suppresses spontaneous oviduct tumorigenesis in quail. 2015 19

Long-term heat acclimation (AC, 30d/34 degrees C) is a phenotypic adaptation leading to increased thermotolerance during heat stress (HS, 2 h 41 degrees C). AC also renders protection against ischemic/reperfusion (I/R, 30' global ischemia/40' reperfusion) insult via cross-tolerance mechanisms. In contrast to the protected AC phenotype, the onset of acclimation (34 degrees C, AC2d) is characterized by cellular perturbations, suggesting increased susceptibility to HS and I/R insults. In this investigation, we tested the hypothesis that apoptosis resistance is part of the AC repertoire and that, at the initial phase of acclimation (AC2d), cytoprotection is impaired. TUNEL staining and caspase 3 levels in HS and I/R insulted hearts affirmed this hypothesis. To examine the role of the mitochondria in life/death decision in AC2d and 30d AC settings vs. control hearts, we studied the Bcl-2 apoptotic cascade and found increased levels of the anti-apoptotic Bcl-X(L) and decreased levels of the pro-apoptotic death promoter Bad in hearts from AC2d and AC animals. In these groups, cytochrome c (cyt c) was elevated in the mitochondria and remained unchanged in the cytosol. This adaptation was insufficient to negate apoptosis in AC2d rats. At this early acclimation phase (and in controls), increased caspase 8 activity confirmed activation of the extrinsic (Fas ligand) apoptosis pathway. In conclusion, the elevated Bcl-X(L)/Bad ratio and decreased cyt c leakage to the cytosol are insufficient to protect the heart and interactions with additional cytoprotective pathways involved in acclimation (elevated HSP70, ROS, and sarcolemmal adaptations to abolish extrinsic apoptosis pathways) are required to induce the apoptosis-resistant AC phenotype.
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PMID:Long- but not short-term heat acclimation produces an apoptosis-resistant cardiac phenotype: a lesson from heat stress and ischemic/reperfusion insults. 2022 56


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