Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00627 (MAP)
 15,705 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Roles of ovarian progesterone secretion and maternal nutrition in fetal development were investigated in a species that normally experiences considerable embryonic and fetal mortality. Pregnancies were maintained in 81% of Yorkshire pigs during prolonged starvation (e.g., 40 days; 0 kcal/day, water only) in either the middle third (days 30-70) or last third (days 70-110) of gestation compared with 100% in full-fed controls (7,028 kcal/day). In spite of severe maternal deprivation, fetal survival rates averaged 65% in starved dams and 63% in controls; mean number of living fetuses was 9.9 in starved and 9.6 in control dams. Fetal growth was reduced by maternal starvation during the middle third, but not the last third of pregnancy. Placental insufficiency was the primary cause of reduced fetal growth and resulted in abortion in a few of the dams. Progesterone in peripheral serum of dams starved either during middle or late pregnancy was maintained at levels similar (P greater than 0.05) to those in controls. Abortion occurred in starved dams only when serum progesterone concentrations dropped to less than 10 ng/ml within 3 days before loss of conceptuses.
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PMID:Progesterone secretion and fetal development during prolonged starvation in the pig. 43 95

The relationships of maternal nutrition and progesterone secretion to prenatal fetal loss and neonatal survival and growth were investigated in domesticated pigs that normally experience 40% fetal loss. Yorkshire pigs were subjected to prolonged starvation (40 days; 0 kcal/day; water only) in either the middle third or last third of pregnancy and then gradually realimented to a full diet and allowed to advance to parturition; controls received a full diet (7,028 kcal/day) throughout gestation. Pregnancies were maintained in 74% of the pigs starved during either middle or late gestation compared to 100% in controls. In dams starved from days 30--70, progesterone levels remained similar to controls, but were maintained at lower levels during realimentation between days 72 and 99. Progesterone levels in dams starved days 50--90 and controls were similar from days 50 to 130. At parturition, litter size in starved dams (9.4) was similar to full-diet controls (8.0) although birth weight and neonatal growth of piglets were reduced markedly from dams starved in middle or late pregnancy. These results indicate that severe maternal nutrient deprivation during the middle or last third of gestation has little effect on ovarian progesterone secretion and is not a major limitation to fetal survival in this litter-bearing species. Maternal nutrient deprivation imposes a significant detrimental effect, however, on birth weight and neonatal growth to 80 days of age.
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PMID:Maternal starvation and progesterone secretion, litter size, and growth in the pig. 47 53

3-Mercaptopicolinate (3-MPA) is a specific inhibitor of phosphoenolpyruvate carboxykinase (PEP CK). In vivo the hypoglycaemic action of 3-MPA in 24 h-starved rats was abolished on intragastric glucose refeeding. Nonetheless, 3-MPA decreased hepatic glycogen content and rate of synthesis in starved animals re-fed glucose. The inference is that on re-feeding after starvation hepatic glycogen is synthesised mainly de novo via glyconeogenesis involving PEP CK. 3-MPA increased hepatic lipogenesis in water- and glucose-fed normal and diabetic rats. This increase is presumed to result from inhibition of PEP CK and consequent diversion of pyruvate from gluconeogenesis to lipogenesis. In contrast, 3-MPA inhibited brown-fat lipogenesis in water- and glucose-fed rats.
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PMID:Direction of carbon flux in starvation and after refeeding: in vitro and in vivo effects of 3-mercaptopicolinate. 667 46

The inhibition of cell death by growth factors plays a key role in the maintenance of the haematopoietic system homeostasis. However the mechanisms involved in this inhibition are still poorly understood. In order to determine if inhibition of apoptosis by growth factors is dependent only on the expression of survival genes, we have studied that process in the bone marrow derived IL-3 dependent cell line Baf-3. We show that, following IL-3 starvation, mRNA and protein levels of Bcl-X but not Bcl-2 decrease rapidly preceeding the onset of death. The death of IL-3 starved cells is asynchronous, starting between 6 to 8 h with 50% death being reached after 10 to 12 h. At any time point, apoptosis can be rapidly inhibited by growth factor re-addition. This has allowed us to determine that the inhibition of apoptosis by growth factor takes place at two levels. The first one, which we have called short term inhibition, is independent of mRNA and protein synthesis i.e. it takes place in the absence of survival gene neosynthesis and can be demonstrated during the first 6 h following growth factor re-addition. The second one corresponds to long-term survival-more than 24 h survival-and is strongly correlated with the induction of Bcl-X but not Bcl-2 gene expression. This induction of Bcl-X by IL-3 is shown to be dependent on MAP-kinase activation.
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PMID:In bone marrow derived Baf-3 cells, inhibition of apoptosis by IL-3 is mediated by two independent pathways. 905 39

In the present study we have investigated a possible role for the proline-rich SH2 domain protein Shb as a regulator of expression or activity of certain SH3 domain proteins and MAP kinase. The expression of the Shb binding proteins Eps8, Src, and p85 PI3-kinase, PI3-kinase activity, and MAP kinase activation were assessed in wild-type NIH3T3 cells and in NIH3T3 cells overexpressing the Shb cDNA. In addition, the expression of the SH3 domain STAT1 proteins was assessed in wild-type and Shb overexpressing cells. The Eps8 protein content and Eps8 mRNA steady-state levels were downregulated, whereas the protein contents of Src and p85 PI3-kinase were unaffected by Shb overexpression. There was, however, an increased basal PI3-kinase activity in Shb transfected cells after a 3-h serum starvation. Increased steady-state levels of STAT1 mRNA were accompanied by an increased STAT1 protein content in Shb overexpressing cells. Shb overexpression was not associated with an altered activation of p44 or p42 MAP kinases in response to PDGF stimulation. The data presented in this study suggest novel functions for the adaptor protein Shb regulating the expression of certain signal-transducing SH3 domain proteins and modulating PI3-kinase activity.
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PMID:Modulation of Src homology 3 proteins by the proline-rich adaptor protein Shb. 908 67

Sphingosine 1-phosphate (S1P) regulates cell proliferation, apoptosis, motility, and neurite retraction. Contradictory reports propose that S1P acts as either an intracellular second messenger or an extracellular ligand for cell-surface receptors. Hence, the precise signaling mechanisms mediating the diverse cellular effects of S1P remain to be determined. Here, we investigate whether S1P stimulation of cell proliferation, survival, and related signaling events can be mediated by the recently cloned Edg family members of G protein-coupled receptors. We observed that S1P treatment significantly increased proliferation of HTC4 hepatoma cells stably transfected with human S1P receptor Edg3 or Edg5, which was attributable to stimulation of cell growth and inhibition of apoptosis caused by serum starvation. Edg3 and Edg5 transduced S1P-evoked signaling events relevant to cell proliferation and survival, including activation of the ERK/MAP kinases, and immediate-early induction of c-Jun and c-Fos. Trancriptional activation of reporter genes for the c-fos promoter and the serum response element by Edg3 and Edg5 transfected in Jurkat cells was inhibited by pertussis toxin and C3 exoenzyme, implicating G(i/o)- and Rho-dependent pathways. Our data also indicated that Edg3 and Edg5 mediated the serum response element activation through transcriptional factors Elk-1 and serum response factor. Thus, specific G protein-coupled receptors Edg3 and Edg5 account for, at least in part, S1P-induced cell proliferation, survival, and related signaling events.
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PMID:Sphingosine 1-phosphate-induced cell proliferation, survival, and related signaling events mediated by G protein-coupled receptors Edg3 and Edg5. 1061 17

Chronic hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis and hepatocellular carcinoma (HCC) worldwide. The HCV capside core is a multifunctional protein with regulatory functions that affects transcription and cell growth in vitro and in vivo. Here, we show that both HCV genotype 1a and 3 core proteins activate MEK1 and Erk1/2 MAP kinases and that the costitutive expression of the HCV core results in a high basal activity of Raf1 and MAP/kinase/kinase, as determined by endogenous Raf1 in vitro kinase assay and immunodetection of hyperphosphorylated Erk1 and Erk2 even after a serum starvation. Moreover, the activation of both Erk1/2 and the downstream transcription factor Elk-1 in response to the mitogenic stimulus EGF is significantly prolonged. The sustained response to EGF in cells expressing the HCV core occurs despite a normal induction of the MAP phosphatases MKP regulatory feedback and is likely due to the costitutive activation of Raf-1 activity. The ability of HCV core proteins to directly activate the MAP kinase cascade and to prolong its activity in response to mitogenic stimuli may contribute to the neoplastic transformation of HCV infected liver cells.
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PMID:Sustained activation of the Raf/MEK/Erk pathway in response to EGF in stable cell lines expressing the Hepatitis C Virus (HCV) core protein. 1142 Jun 71

The expression of oncofetal H19 RNA and its localization/cellular source was analyzed in synovial tissue (ST) and isolated synovial macrophages (Mphi) or synovial fibroblasts (SFBs) by reverse transcriptase-polymerase chain reaction (RT-PCR), in situ hybridization, and immunohistochemistry. RT-PCR showed significantly higher H19 expression in ST from patients with rheumatoid arthritis (RA) (P = 0.000) and osteoarthritis (OA) (P = 0.009) than in normal/joint trauma controls (N/JT), but comparable levels in reactive arthritis. In situ hybridization demonstrated strong signals in all RA-ST samples (n = 8), with > or =85% positive cells in the lining layer, diffuse infiltrates, and stroma regions. In lymphoid aggregates and endothelial cells only 20% were positive. RA-ST contained a significantly higher percentage of strongly positive lining cells than OA-ST and N/JT-ST. H19 RNA was expressed in both Mphi and SFBs, as confirmed by RT-PCR in isolated RA Mphi and SFBs (n = 3). In RA-SFBs, low constitutive H19 RNA expression in culture (10% fetal calf serum) was strongly increased on starvation (3.5-fold, 1% fetal calf serum), with or without the addition of interleukin-1beta (10 to 100 U/ml), tumor necrosis factor-alpha (1 to 25 ng/ml), or platelet-derived growth factor-BB (2.5 to 10 U/ml). In OA-SFBs, this starvation-induced increase was lower (twofold), reaching significant differences compared with RA-SFBs after stimulation with interleukin-1beta and platelet-derived growth factor-BB. In both RA- and OA-SFBs, the MAP-kinase ERK-1/2 pathway and the phosphatidylinositol-3 kinase pathway influenced H19 RNA expression, as shown by inhibitor studies. Significant overexpression of H19 RNA and its increased sensitivity to starvation/cytokine regulation in RA suggests a pathogenetic role of this oncofetal gene, possibly reflecting embryonal dedifferentiation of the adult ST and/or ongoing inflammatory/oxidative stress.
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PMID:Detection of oncofetal h19 RNA in rheumatoid arthritis synovial tissue. 1293 31

Embryonic carcinoma (EC) cells and embryonic stem (ES) cells have short cell cycles and, accordingly, proliferate very fast. Serum starvation does not suppress proliferation of EC and ES cells that allows to assume independence of their proliferation from the activity of cascades induced by serum. In the present work, we used flow cytometry to investigate how specific MAP-kinase and PI3-kinase inhibitors may influence proliferation and cell cycle of EC F9 cells. It is established that inhibitors of ERK-, JNK- and p38-kinases do not suppress EC F9 cell proliferation. It is possible to assume that proliferation of EC cells is supported by constitutive activity of down-stream cell cycle regulators, for example, E2F1 transcription factor. Since PI3-kinase inhibitor LY294002 causes reduction of S-phase and accumulation of G1-phase F9 cells, PI3-kinase mediated cascades seem to be constantly activated and involved in phosphorylation of important cell cycle regulators. The analysis of transcription of immediate-early genes in undifferentiated cells has shown that c-fos and c-jun genes are strongly activated by serum, and that ERK-kinase plays the main role in activation of c-fos transcription, while activation of c-jun transcription depends predominantly on p38-kinase. It is necessary to note that PI3-kinase inhibitor increases effect of serum stimulation of c-fos promoter. It means that the PI3-kinase dependent cascade negatively influences the cascade, which activates c-fos transcription. Thus, the transcription of c-fos and c-jun is not connected with of EC F9 cell proliferation. The proliferation of these cells depends on PI3-kinase activity.
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PMID:[PI 3-kinase activity is necessary for F9 mouse embryonic carcinoma cell proliferation]. 1511 28

The cercariae of Schistosoma mansoni become transformed into schistosomula during host skin penetration. We have found that large acidophilic compartments are detected in schistosomula but not in cercariae or in any other stages of the parasite by use of the fluorescent dye LysoTracker, a dye specific for mammalian lysosomes. Some of these large acidic compartments incorporated monodansylcadaverine, a specific dye for autophagosomes. We have used potent inhibitors (wortmannin and 3-methyladenine) and a potent inducer (starvation) of autophagy to show that the pathway to the formation of the acidic compartments requires specific molecular signals from the environment and from the genome. Certain doses of ultraviolet light inhibited significantly the formation of the acidic compartments, which may indicate disruption of the lysosome/autophagosome pathway. We have also defined two proteins that are commonly associated with lysosomes and autophagosomes in mammalian cells, the microtubule-associated membrane protein (MAP-LC3) and lysosome-associated membrane protein (LAMP-1), in extracts of schistosomula. We suggest that the autophagy pathway could be developed in transformed schistosomula.
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PMID:The role of acidic organelles in the development of schistosomula of Schistosoma mansoni and their response to signalling molecules. 1579 14


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