Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heterozygous mutations in the type II receptor for bone morphogenetic protein (BMPR-II) and dysfunction of BMPR-II have been implicated in patients with primary pulmonary hypertension (PH). To clarify the possible involvement of BMP and BMPR-II in the development of hypoxic PH, the expression of BMP-2, BMPR-II, and their downstream signals were investigated in rat lung under normal and hypoxic conditions by RT-PCR, immunoblot, and immunohistochemical methods. In rats under normal conditions, BMP-2 is localized in the endothelium of the pulmonary artery, whereas BMPR-II is abundantly expressed in the endothelium, smooth muscle cells, and adventitial fibroblasts. After 0.5 and 3 days of exposure to hypoxia, upregulation of BMP-2 was observed in the intrapulmonary arteries. The change was accompanied by activation of its downstream signaling, p38 MAPK, and Erk1/2 MAPK, and the apoptotic process, measured by caspase-3 activity and TdT-mediated dUTP nick end labeling-positive cells. In contrast, a significant decrease in the expression of BMPR-II and inactivation of p38 MAPK and caspase-3 were observed in the pulmonary vasculature after 7-21 days of hypoxia exposure. Because BMP-2 is known to inhibit proliferation of vascular smooth muscle cells and promote cellular apoptosis, disruption of BMP signaling pathway through downregulation of BMPR-II in chronic hypoxia may result in pulmonary vascular remodeling due to the failure of critical antiproliferative/differentiation programs in the pulmonary vasculature. These results suggest abrogation of BMP signaling may be a common molecular pathogenesis in the development of PH with various pathophysiological events, including primary and hypoxic PH.
Am J Physiol Lung Cell Mol Physiol 2006 Mar
PMID:Downregulation of type II bone morphogenetic protein receptor in hypoxic pulmonary hypertension. 1636 57

Choriocarcinoma is a malignant trophoblast-derived tumour, which can arise in any type of gestation. Cell proliferation assays showed that interferon gamma (IFNgamma) alone significantly inhibited proliferation of choriocarcinoma JAR and JEG-3 cells. TdT (terminal deoxynucleotidyl transferase)-mediated dUDP nick-end labelling (TUNEL) assays and Hoechst staining indicated that IFNgamma alone could not induce apoptosis of JAR and JEG-3 cells, but IFNgamma could enhance the sensitivity of JAR cells to etoposide-induced apoptosis. RT-PCR and western blotting were performed to detect expression of apoptosis-related molecules IFNgammaR, interferon regulatory factor-1 (IRF-1), p53 and pro-caspase 3. In JAR cells, etoposide increased expression of the proteins including IFNgammaR, p53 and pro-caspase 3 as well as IRF-1 mRNA and IFNgamma-pretreatment apparently promoted up-regulation of these molecules expression. In addition, the responses of IRF-1, p53 and pro-caspase 3 expression to IFNgamma pretreatment were dose dependent. IRF-1 knock down assays demonstrated that IRF-1 directly mediated IFNgamma pretreatment enhanced sensitivity of JAR cells to etoposide-induced apoptosis and that pro-caspase 3 was one of the target genes of IRF-1.
Mol Hum Reprod 2006 Feb
PMID:IFNgamma pretreatment sensitizes human choriocarcinoma cells to etoposide-induced apoptosis. 1646 99

Stress-activated protein kinase/c-Jun kinase (SAPK/JNK) is thought to be necessary for preimplantation embryonic development (Maekawa et al., 2005). However, media increases SAPK/JNK phosphorylation and these levels negatively correlate with embryonic development (Wang et al., 2005). Culture-induced stress could confuse analysis of the role of SAPK in development. In this study, we tested how SAPK/JNK inhibitors influence embryonic development in optimal and non-optimal media and define the contribution of cell survival and proliferation to the embryonic response to these media. SAPK/JNK inhibitors retard embryonic development in suboptimal Ham's F10, but improve development in optimal potassium (K+) simplex optimized media (KSOM) +AA. In KSOM + amino acids (KSOM+AA), two SAPK/JNK inhibitors increase the rate of cavitation and hatching. These data suggest that (i) SAPK/JNK mediates the response to culture stress, not normal preimplantation embryonic development and (ii) SAPK/JNK inhibitors may be useful in ameliorating embryo stress caused by culture. To define the effects of media, we assayed the contribution of cell survival and proliferation and the differences in total cell number of cultured embryos. Embryos cultured from E3.5+24 h in the suboptimal medium (Ham's F10) induced significant but small increases in TdT (terminal deoxynucleotidyl transferase)-mediated dUDP nick-end labelling (TUNEL) positive cells. Bromodeoxyuridine (BrdU) incorporation in suboptimal Ham's F10 was significantly lower than in optimal KSOM+AA, suggesting that cell cycle arrest also contributes to slower increase in cell number in stressful media. This is the first report where TUNEL and BrdU were both assayed to define the relative contribution of cell cycle/S phase commitment and apoptosis to lessened cell number increase during embryo culture.
Mol Hum Reprod 2006 Apr
PMID:Effects of SAPK/JNK inhibitors on preimplantation mouse embryo development are influenced greatly by the amount of stress induced by the media. 1657

Aims-To identify the role played by apoptosis in tumour regression.Methods-The growth fraction and apoptotic cell loss of four cases of eosinophilic granuloma were investigated using monoclonal antibodies against Ki-67 proliferation marker (MIB-1) antigen and the TdT mediated dUTP-biotin 3'-OH nick end labelling (TUNEL) method. These data were then compared with the clinical growth rate.Results-Only the Langerhans histiocytic cells, which reacted positively with anti-S-100 protein antibody, were immunolabelled with antibodies to proliferating cell nuclear antigen and Ki-67 antigen (MIB-1). Many apoptotic figures of histiocytic cells were also detected in all cases by the TUNEL method. In a patient whose tumour clinically showed spontaneous regression, the TUNEL staining index gave a higher score than the MIB-1 staining index.Conclusions-The main cause of the spontaneous regression of the tumours was postulated to be programmed cell death (apoptosis).
Clin Mol Pathol 1995 Oct
PMID:Proliferative activity and apoptosis of Langerhans histiocytes in eosinophilic granulomas as evaluated by MIB-1 and TUNEL methods. 1669 16

Flow cytometric analysis of cluster of differentiation (CD) markers in abnormal lymphocyte populations is crucial in the diagnosis of precursor T cell acute lymphoblastic leukemia (T-ALL)/lymphoblastic lymphoma (LBL). The World Health Organization (WHO) suggested immunophenotype for pre-T ALL/LBL typically includes the expression of TdT, cCD3, and CD7, while CD2, CD3, CD4, CD5, CD8, and CD10 are variably expressed. The myeloid antigens CD13 and CD33 are usually positive, whereas CD117 and cCD79a are infrequently expressed. Furthermore, there is frequent dual expression of CD4 and CD8. In the present investigation, 19 cases of pre-TALL/LBL were analyzed for selected CD marker expression. Fifteen of 19 cases studied were evaluated for TdT, cCD3, and cCD79a expression. Eleven (73.3%) positively expressed TdT, 15 (100%) positively expressed cCD3, and 9 (60%) positively expressed cCD79a. Of the 17 cases analyzed for CD7, CD5, and CD10 expression, CD7 and CD5 were positive in all 17 (100%) cases, whereas CD10 was positive in 8 (47.1%) cases. Of the 18 cases evaluated for CD2, CD3, CD4, CD8, and dual expression of CD4 and CD8, CD2 was expressed in 14 (77.8%), while CD3 was expressed in 7 (38.9%) cases. CD4 was positive in 11 (61.1%), and CD8 was expressed in 9 (50%). Dual expression of CD4 and CD8 occurred in only 4 (22.2%) of the cases. Of the 16 analyzed for CD13, CD33, and CD117, only 1 case (6.3%) expressed CD13, while 2 (12.5%) cases expressed CD33 and CD117. Thus, these data point to the need for a more extensive study to reevaluate the current WHO defined immunophenotype used in the diagnosis of pre-TALL/LBL.
Exp Mol Pathol 2006 Oct
PMID:The immunophenotype of pre-TALL/LBL revisited. 1690 18

Idiopathic pulmonary arterial hypertension (IPAH) is characterized by plexiform vascular lesions, which are hypothesized to arise from deregulated growth of pulmonary artery endothelial cells (PAEC). Here, functional and molecular differences among PAEC derived from IPAH and control human lungs were evaluated. Compared with control cells, IPAH PAEC had greater cell numbers in response to growth factors in culture due to increased proliferation as determined by bromodeoxyuridine incorporation and Ki67 nuclear antigen expression and decreased apoptosis as determined by caspase-3 activation and TdT-mediated dUTP nick end labeling assay. IPAH cells had greater migration than control cells but less organized tube formation in in vitro angiogenesis assay. Persistent activation of signal transducer and activator of transcription 3 (STAT3), a regulator of cell survival and angiogenesis, and increased expression of its downstream prosurvival target, Mcl-1, were identified in IPAH PAEC. A Janus kinase (JAK) selective inhibitor reduced STAT3 activation and blocked proliferation of IPAH cells. Phosphorylated STAT3 was detected in endothelial cells of IPAH lesions in vivo, suggesting that STAT3 activation plays a role in the proliferative pulmonary vascular lesions in IPAH lungs.
Am J Physiol Lung Cell Mol Physiol 2007 Sep
PMID:Hyperproliferative apoptosis-resistant endothelial cells in idiopathic pulmonary arterial hypertension. 1760 94

The aim of our in-vitro experiments was to examine, whether leptin can directly control functions of avian ovarian cells and to outline potential intracellular mediators of its effects. Granulosa cells or fragments of ovarian follicular wall were cultured with leptin (0, 1, 10 or 100 ng/mL medium). The expression of peptides involved in apoptosis (TdT, bax, its binding protein, bcl-2, ASK-1 and p53), cell cycle-related peptides (PCNA and cyclin B1), release of hormones (progesterone, testosterone, estradiol, arginine-vasotocin), as well as the expression of protein kinases (PKA, MAPK/ERK1,2 and CDK/p34) in the ovarian cells were examined by using immunocytochemistry, TUNEL, SDS-PAGE-Western immunoblotting, EIA and RIA. It was found that leptin inhibited expression of all markers of cytoplasmic apoptosis (bax, ASK-1 and p53), stimulated expression of anti-apoptotic peptide bcl-2, but did not affect nuclear DNA fragmentation (TdT). Furthermore, leptin inhibited expression of PCNA (marker of S-phase of mitosis), but not of cyclin B1 (marker of G phase of cell cycle). Moreover, it promoted release of progesterone and estradiol, suppressed release of testosterone, but did not affect arginine-vasotocin. Finally, leptin inhibited expression of MAPK/ERK1,2 and CDK/p34 and stimulated expression of PKA. The present observations demonstrate that leptin can directly control basic chicken ovarian functions - inhibit cytoplasmic apoptosis and proliferation (S-phase, but not G-phases of mitosis), regulate secretory activity (release of steroids, but not nonapeptide hormone) and expression of MAPK, PKA and CDC2, which might be potential intracellular mediators of leptin action.
Comp Biochem Physiol A Mol Integr Physiol 2007 Oct
PMID:Leptin directly controls proliferation, apoptosis and secretory activity of cultured chicken ovarian cells. 1760 68

The dynamics of immunoglobulin rearrangements and selection, which depend on age, antigen exposure and tolerance functions, are only partly understood. Thus, we analyzed and compared the lambda chain immunoglobulin repertoire of individual IgD+ human neonatal B cells with the adult peripheral B cell VlambdaJlambda repertoire. Some Vlambda genes, 4C, 2A2, 2B2, 5A, 1G and 4B, were overexpressed in the non-productive neonatal repertoire, whereas other Vlambda genes (2E, 2A2, 3H, 2B2, 1C and 1G) were overexpressed in the productive repertoire. The adult B cell repertoire revealed nearly the same predominance of genes in the non-productive and productive repertoire. A comparison of the non-productive and productive repertoire indicated that the genes 3H and 1C were positively selected, whereas the genes 4C, 2A1, 3I, 5A, 9A, 4A and 4B were negatively selected. All four functional Jlambda genes were used in both repertoires. Jlambda2/3 was used mainly. Insertions of non-templated nucleotides at the VlambdaJlambda-junction by the enzyme TdT were less frequent as compared to the adult, but the CDR3 length was the same. Comparison of CD5+IgD+ and CD5-IgD+ B cells revealed no differences between neonatal productive rearrangements. However, the genes 1C and 1G were used more often in the non-productive repertoire of CD5+ B cells, whereas gene 4B was used significantly more frequent in CD5- B cells. These data provide evidence that the primary usage and subsequent selection of Vlambda genes in the neonate are surprisingly comparable with the adult. This suggests that selection into the productive Vlambda repertoire in principal might be driven mainly by autoantigens in the newborn, as well as in adulthood, since newborns have not been exposed to exogenous antigens.
Mol Immunol 2008 Jan
PMID:The lambda gene immunoglobulin repertoire of human neonatal B cells. 1767 56

According to WHO, several T-cell immunophenotypic markers may be aberrantly expressed in acute myeloid leukemia (AML). TdT may be expressed in greater than one-third of cases, and CD2 and CD7 may be expressed frequently at low intensity; however, the T-cell lineage specific antigen CD3 is usually absent. In this investigation, 30 cases of AML were evaluated for CD2, CD3, CD5, CD7, CD8 and TdT expression, and mean fluorescence intensities (MFI). Of the 3 (10%) cases positive for CD3 and CD8, 1 was bright (MFI>501), and 2 cases were moderate. TdT was moderately expressed in 4 (13.3%) cases with MFI values between 301 and 500. CD2 and CD5 were positive in 5 (16.7%) cases. While CD2 was moderate in all 5 cases, CD5 was bright in 3, moderate in 1 and dim in 1. Of the 15 (50%) cases positive for CD7, 9 were bright, 5 were moderate, and 1 was dim with a MFI value between 201 and 300. These data indicate that CD2 and CD7 may be frequently expressed at greater intensities than WHO specified. These results point to the need for a more extensive study to evaluate the potential prognostic significance of aberrant T-cell marker expression in AML.
Exp Mol Pathol 2007 Dec
PMID:Aberrant expression of T-cell markers in acute myeloid leukemia. 1792 77

Galectins have recently emerged as central regulators of the immune system. We have previously demonstrated that carbohydrate-dependent binding of galectin-2 induces apoptosis in activated T cells. Here, we investigate the potential therapeutic effect of galectin-2 in experimental colitis. Galectin-2 expression and its binding profile were determined by immunohistochemistry. Acute and chronic colitis was induced by dextran sodium sulfate administration and in a T-cell transfer colitis model. Apoptosis was assessed by TdT-mediated dUTP-biotin nick-end labeling, and cytokine secretion was determined by cytometric bead array. We show that galectin-2 was constitutively expressed mainly in the epithelial compartment of the mouse intestine and bind to lamina propria mononuclear cells. During colitis, galectin-2 expression was reduced, but could be restored to normal levels by immunosuppressive treatment. Galectin-2 treatment induced apoptosis of mucosal T cells and thus ameliorated acute and chronic dextran-sodium-sulfate-induced colitis and in a T-helper-cell 1-driven model of antigen-specific transfer colitis. Furthermore, the pro-inflammatory cytokine release was inhibited by galectin-2 treatment. In preliminary toxicity studies, galectin-2 was well tolerated. Our study provides evidence that galectin-2 induces apoptosis in vivo and ameliorates acute and chronic murine colitis. Furthermore, galectin-2 has no significant toxicity over a broad dose range, suggesting that it may serve as a new therapeutic agent in the treatment of inflammatory bowel disease.
J Mol Med (Berl) 2008 Dec
PMID:Galectin-2 induces apoptosis of lamina propria T lymphocytes and ameliorates acute and chronic experimental colitis in mice. 1806 31


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