Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UNIPROT:P10415 (Bcl-2)
33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Wilms' tumor gene Wt1 is unique among tumor suppressors because of its requirement for the development of certain organs. We recently described de novo expression of Wt1 in myocardial blood vessels of ischemic rat hearts. The purpose of this study was to analyze the mechanism(s) of hypoxic/ischemic induction of Wt1. We show here that Wt1 mRNA and protein is up-regulated in the heart and kidneys of rats exposed to normobaric hypoxia (8% O2). Ectopic Wt1 immunoreactivity was detected in renal tubules of hypoxic rats, which also expressed the antiapoptotic protein Bcl-2 and contained significantly fewer TUNEL-positive cells than in normoxic kidneys. Wt1 expression was enhanced in the osteosarcoma line U-2OS and in Reh lymphoblast cells that were grown either at 1% O2 or in the presence of CoCl2 and desferrioxamine, respectively. The promoter of the Wt1 gene was capable of mediating expression of a luciferase reporter in response to hypoxia. We identified a hypoxia-responsive element in the Wt1 sequence that bound to hypoxia-inducible factor-1 (HIF-1) and was required for activation of the Wt1 promoter by CoCl2 and HIF-1. These findings demonstrate that Wt1 expression can be stimulated by hypoxia, which involves activation of the Wt1 promoter by HIF-1.
...
PMID:Oxygen-regulated expression of the Wilms' tumor suppressor Wt1 involves hypoxia-inducible factor-1 (HIF-1). 1273 1

Mammalian tRNA 3' processing endoribonuclease (3'-tRNase) can cleave any RNA at any site under the direction of small guide RNA (sgRNA) in vitro. sgRNAs can be as short as heptamers, which are much smaller than small interfering RNAs of approximately 21 nt. Together with such flexibility in substrate recognition, the ubiquity and the constitutive expression of 3'-tRNase have suggested that this enzyme can be utilized for specific cleavage of cellular RNAs by introducing appropriate sgRNAs into living cells. Here we demonstrated that the expression of chloramphenicol acetyltransferase can be downregulated by an appropriate sgRNA which is introduced into Madin-Darby canine kidney epithelial cells as an expression plasmid or a synthetic 2'-O-methyl RNA. We also showed that 2'-O-methyl RNA heptamers can attack luciferase mRNAs with a high specificity and induce 3'-tRNase-mediated knock-down of the mRNAs in 293 cells. Furthermore, the MTT cell viability assay suggested that an RNA heptamer can downregulate the endogenous Bcl-2 mRNA in Sarcoma 180 cells. This novel sgRNA/3'-tRNase strategy for destroying specific cellular RNAs may be utilized for therapeutic applications.
...
PMID:Intracellular mRNA cleavage by 3' tRNase under the direction of 2'-O-methyl RNA heptamers. 1288 94

Mcl-1 is an antiapoptotic member of the Bcl-2 family whose protein and mRNA have a short half-life. In this report, we studied the changes in Mcl-1 protein and mRNA expression induced by staurosporine and aspirin. Both drugs induced apoptosis in Jurkat cells and reduced the levels of Mcl-1 protein. The caspase inhibitor Z-VAD.fmk and the proteasome inhibitor MG132 partially protected Mcl-1 from decay, indicating that both caspase-dependent and proteasome pathways are involved during apoptosis. Staurosporine also reduced Mcl-1 mRNA levels and this reduction was mostly caspase-dependent. In addition, staurosporine reduced the transcriptional activity of the Mcl-1 promoter fused to a luciferase gene reporter more than actinomycin D, a general inhibitor of transcription. Thus, we conclude that staurosporine down-regulates Mcl-1 mRNA levels by inhibiting transcription in a caspase-dependent manner and reduces Mcl-1 protein levels by a caspase-independent post-transcriptional mechanism. In contrast aspirin, at doses and times that induced loss of viability and decay of Mcl-1 protein, had no effect on Mcl-1 mRNA levels. Aspirin rapidly inhibited de novo protein synthesis before caspase activation. Moreover, the translational factor eIF2alpha was transiently phosphorylated and therefore inhibited very soon after aspirin treatment. Aspirin also inhibited the luciferase reporter activity of several attached promoter constructs, but it did not affect the luciferase activity of a construct containing an internal ribosome entry site (IRES) in its mRNA 5(')UTR. We conclude that staurosporine inhibits transcription and translation, whereas aspirin only inhibits cap-dependent translation. Treatment with cycloheximide, at doses that inhibit protein synthesis without affecting cell viability, also induced Mcl-1 protein decay. Mcl-1 disappearance might be necessary but not sufficient for the induction of apoptosis by staurosporine and aspirin. A model for the control of Mcl-1 during drug-induced apoptosis is presented.
...
PMID:Transcriptional and translational control of Mcl-1 during apoptosis. 1294 Dec 95

We investigated the transfection efficiency mediated by asialoganglioside-containing cationic liposomes. Previously we reported that monosialoganglioside GM(1) (GM(1a)) enhanced transfection efficiency. In this study, we investigated the effects of sialic acid in gangliosides on transfection efficiency. Two mammalian culture cell lines HeLa and HepG2 were transfected with luciferase plasmids (pGL3) using cationic liposomes which contain monosialoganglioside GM(1) (GM(1a)) or its asialic counterpart, asialoganglioside GM(1) (GA(1)). Both GM(1a) and GA(1) enhanced the efficiency of transfection mediated by cationic liposomes, and GA(1) exhibited higher efficiency than GM(1a) in both cell lines. Transfection efficiency of ganglioside-containing liposomes was also assessed by the effects of antisense oligonucleotides (AS-ODN) for bcl-2 gene, which suppresses apoptotic cell death. Western blotting analysis revealed that the expression of Bcl-2 was decreased by AS-ODN, and the reduction of protein expression in cells treated with GA(1)-containing liposomes was more remarkable than that with GM(1a)-containing liposomes. Furthermore, the induction rate of apoptosis was higher in cells treated with AS-ODN with GA(1)-containing liposomes. Together with the results obtained by luciferase assay mentioned above, the removal of sialic acid from ganglioside causes the enhancement of efficiency of transfection mediated by cationic liposomes.
...
PMID:Asialoganglioside enhances the efficiency of gene transfection mediated by cationic liposomes with a cationic cholesterol derivative. 1295 76

Paget's disease of bone is characterized by an increase in both the size and the number of bone-resorbing osteoclasts. An important regulator of osteoclast activity is the process of apoptosis, and any aberration in this process could lead to increased osteoclasis. Analysis using human apoptosis cDNA expression arrays revealed that the apoptotic suppressor, Bcl-2, showed a marked increase in expression in Pagetic bone. In situ hybridization (ISH) and computer-assisted image analysis confirmed that the levels of Bcl-2 transcripts were significantly (p<0.0001) increased in Pagetic osteoclasts. The Bcl-2:Bax transcript ratios were similarly elevated. These findings were confirmed by immunohistochemistry. The Bcl-2 gene promoter sequence from 20 Pagetic patients and controls was analysed. Single nucleotide mutations were identified in three of the Paget's patients and one of the controls. Luciferase reporter analysis showed that the mutations induced a basal 12-fold increase and hydrogen peroxide-induced 19-fold increase in luciferase expression, compared with the normal construct. It is concluded that in Paget's disease, there is an increase in the expression of genes that are involved in the inhibition of apoptosis, notably Bcl-2. The increase in Bcl-2 may be explained in some patients by mutations in the Bcl-2 gene promoter. These results provide a potential explanation for the dramatic increase in osteoclasis seen in patients with Paget's disease.
...
PMID:Apoptotic gene expression in Paget's disease: a possible role for Bcl-2. 1459 64

beta-Lapachone is a naturally occurring quinone obtained from the bark of the lapacho tree (Tabebuia avellanedae) with cancer chemopreventive properties. The objective of the present study was to investigate the effect of beta-lapachone on the cell growth and apoptosis in human colon carcinoma tumor cell line HCT-116. Exposure of HCT-116 cells to beta-lapachone resulted in growth inhibition and induction of apoptosis in a dose-dependent manner as measured by hemocytometer counts, fluorescence microscopy and flow cytometric analysis. This increase in apoptosis was associated with a decrease in Bcl-2 protein expression, an increase in caspase-3 activity, a decrease in intact poly(ADP-ribose) polymerase protein levels and degradation of beta-catenin. After beta-lapachone treatment, the nuclear protein levels of NF-kappaB and the activity of NF-kappaB-DNA binding were markedly decreased. beta-Lapachone treatment also resulted in inhibition of the transcriptional activity of NF-kappaB-luciferase reporter plasmid suggesting that beta-lapachone-induced apoptosis may be partly regulated through the inactivation of NF-kappaB.
...
PMID:beta-Lapachone-induced apoptosis is associated with activation of caspase-3 and inactivation of NF-kappaB in human colon cancer HCT-116 cells. 1459 80

Silibinin, the flavonoid found in the milk thistle, has been shown to suppress cell growth and exhibit anti-cancer effects. Some flavonoids were reported to inhibit angiogenesis which is essential for tumor growth and metastasis. In this study, to clarify the underlying mechanisms for the anti-cancer effect of silibinin, we examined the effects of silibinin on human endothelial ECV304 cells. Silibinin was found to suppress the growth and induce the apoptosis of ECV304 cells. The induction of apoptosis by silibinin was confirmed by ladder-patterned DNA fragmentation, cleaved and condensed nuclear chromatin and DNA hypoploidy. Silibinin could effectively inhibit constitutive NF-kappaB activation as revealed by electrophoretic mobility shift assay and NF-kappaB-dependent luciferase reporter study. Consistent with this, silibinin treatment resulted in a significant decrease in the nuclear level of p65 subunit of NF-kappaB. In addition, silibinin treatment caused a change in the ratio of Bax/Bcl-2 in a manner that favors apoptosis. Silibinin also induced the cytochrome c release, activation of caspase-3 and caspase-9 and cleavage of PARP. These results suggest that silibinin may exert, at least partly, its anti-cancer effect by inhibiting angiogenesis through induction of endothelial apoptosis via modulation of NF-kappaB, Bcl-2 family and caspases.
...
PMID:Involvement of NF-kappaB and caspases in silibinin-induced apoptosis of endothelial cells. 1465 75

Kallikrein/kinin has been shown to protect against ischemia/reperfusion-induced myocardial infarction and apoptosis. In the present study, we examined the potential neuroprotective action of kallikrein gene transfer in cerebral ischemia. Adult, male Sprague-Dawley rats were subjected to a 1-hour occlusion of the middle cerebral artery followed by intracerebroventricular injection of adenovirus harboring either the human tissue kallikrein gene or the luciferase gene. Kallikrein gene transfer significantly reduced ischemia-induced locomotor deficit scores and cerebral infarction after cerebral ischemia injury. Expression of recombinant human tissue kallikrein was identified and localized in monocytes/macrophages of rat ischemic brain by double immunostaining. Morphological analyses showed that kallikrein gene transfer enhanced the survival and migration of glial cells into the ischemic penumbra and core, as identified by immunostaining with glial fibrillary acidic protein. Cerebral ischemia markedly increased apoptotic cells, and kallikrein gene delivery reduced apoptosis to near-normal levels as seen in sham control rats. In primary cultured glial cells, kinin stimulated cell migration but inhibited hypoxia/reoxygenation-induced apoptosis in a dose-dependent manner. The effects of kinin on both migration and apoptosis were abolished by icatibant, a bradykinin B2 receptor antagonist. Enhanced cell survival after kallikrein gene transfer occurred in conjunction with markedly increased cerebral nitric oxide levels and phospho-Akt and Bcl-2 levels but reduced caspase-3 activation, NAD(P)H oxidase activity, and superoxide production. These results indicate that kallikrein gene transfer provides neuroprotection against cerebral ischemia injury by enhancing glial cell survival and migration and inhibiting apoptosis through suppression of oxidative stress and activation of the Akt-Bcl-2 signaling pathway.
...
PMID:Kallikrein gene transfer protects against ischemic stroke by promoting glial cell migration and inhibiting apoptosis. 1469 96

Endothelial cells are the primary targets of circulating immune and inflammatory mediators. We hypothesize that interleukin-18, a proinflammatory cytokine, induces endothelial cell apoptosis. Human cardiac microvascular endothelial cells (HCMEC) were treated with interleukin (IL) 18. mRNA expression was analyzed by ribonuclease protection assay, protein levels by immunoblotting, and cell death by enzyme-linked immunosorbent assay and fluorescence-activated cell sorter analysis. We also investigated the signal transduction pathways involved in IL-18-mediated cell death. Treatment of HCMEC with IL-18 increases 1) NF-kappaB DNA binding activity; 2) induces kappaB-driven luciferase activity; 3) induces IL-1beta and TNF-alpha expression via NF-kappaB activation; 4) inhibits antiapoptotic Bcl-2 and Bcl-X(L); 5) up-regulates proapoptotic Fas, Fas-L, and Bcl-X(S) expression; 6) induces fas and Fas-L promoter activities via NF-kappaB activation; 7) activates caspases-8, -3, -9, and BID; 8) induces cytochrome c release into the cytoplasm; 9) inhibits FLIP; and 10) induces HCME cell death by apoptosis as seen by increased annexin V staining and increased levels of mono- and oligonucleosomal fragmented DNA. Whereas overexpression of Bcl-2 significantly attenuated IL-18-induced endothelial cell apoptosis, Bcl-2/Bcl-X(L) chimeric phosphorothioated 2'-MOE-modified antisense oligonucleotides potentiated the proapoptotic effects of IL-18. Furthermore, caspase-8, IKK-alpha, and NF-kappaB p65 knockdown or dominant negative IkappaB-alpha and dominant negative IkappaB-beta or kinase dead IKK-beta significantly attenuated IL-18-induced HCME cell death. Effects of IL-18 on cell death are direct and are not mediated by intermediaries such as IL-1beta, tumor necrosis factor-alpha, or interferon-gamma. Taken together, our results indicate that IL-18 activates both intrinsic and extrinsic proapoptotic signaling pathways, induces endothelial cell death, and thereby may play a role in myocardial inflammation and injury.
...
PMID:Activation of intrinsic and extrinsic proapoptotic signaling pathways in interleukin-18-mediated human cardiac endothelial cell death. 1496 May 79

Peroxisome proliferator activated receptors are nuclear hormone receptors that regulate the expression of genes containing a peroxisome proliferator activated receptor response element. We report here that the human bcl-2 gene contains a functional peroxisome proliferator activated receptor response element in the 3' untranslated region. Peroxisome proliferator activated receptor gamma bound the human bcl-2 peroxisome proliferator activated receptor response element in gel shift assays and co-transfection of this receptor led to increased luciferase activity from a reporter plasmid containing the human bcl-2 peroxisome proliferator activated receptor response element. Examination of peroxisome proliferator activated receptor gamma-transfected cells demonstrated an increased amount of bcl-2 message compared to empty vector-transfected cells. Confocal analyses confirmed that more Bcl-2 protein was present in peroxisome proliferator activated receptor gamma-transfected cells compared to control-transfected cells. The functionality of the increased Bcl-2 protein was examined using resistance to bile salt-induced apoptosis as the endpoint. Peroxisome proliferator activated receptor gamma-transfected cells were almost twice as resistant as control-transfected cells. These data show that PPARgamma can mediate transcription of bcl-2, resulting in an increase in Bcl-2 protein and protection from apoptosis. We discuss these findings with regards to their potential implications for colon carcinogenesis.
...
PMID:Identification of a functional peroxisome proliferator activated receptor response element in the 3' untranslated region of the human bcl-2 gene. 1506 55


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

---