Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protein kinase C has been previously shown both to phosphorylate and to desensitize the ability of the human 5-HT1A receptor to inhibit adenylyl cyclase [Raymond, J. R. (1991) J. Biol. Chem. 266, 14747-14753]. In this study, we examined the effects of short-term treatment with protein kinase A activators on coupling to the inhibition of adenylyl cyclase and on phosphorylation of the human serotonin 5-HT1A receptor in CHO cells that stably express 1200 fmol of receptor/mg of protein. Forskolin induced a concentration- and time-dependent phosphorylation of the receptor that was detectable at 5 min and maximal at 15-30 min with a half-maximal concentration of 10-20 microM. Phosphorylation was also induced by Sp-cAMPS or dibutyryl-cAMP, and blocked by Rp-cAMPS and a pseudosubstrate inhibitor of PKA, but not by heparin (inhibitor of receptor kinase) or sphingosine (inhibitor of PKC). The stoichiometry of phosphorylation induced by forskolin was 1 mol of phosphate per mole of receptor. PKA activators did not induce a measurable desensitization of 5-HT1A receptor-inhibited adenylyl cyclase activity. However, forskolin augmented the desensitization caused by a submaximal concentration of phorbol 12-myristate 13-acetate (300 nM PMA) as evidenced by a rightward shift of the concentration-response curve for 5-HT, and approximately doubled the amount of phosphate incorporated into the receptor by PMA. Forskolin did not augment desensitization or increase the degree of phosphorylation induced by a maximal concentration of PMA (5 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protein kinase A induces phosphorylation of the human 5-HT1A receptor and augments its desensitization by protein kinase C in CHO-K1 cells. 772 77

We analyzed fatty acid make up of cells and organs from autoimmune and immunologically normal mice to determine whether intrinsic differences in composition might be associated with an inflammatory phenotype. Macrophages (MO) isolated from 4-6-week-old MRL lpr/lpr mice were cultured with phorbol ester (PMA), fibroblast growth factor-1 (FGF-1), fibroblast growth factor-2 (FGF-2) and medium control to determine whether these cell signals might induce membrane fatty acid changes. Individual phospholipid analysis showed 8.4- and 5.1-fold increases in phosphatidylcholine arachidonate (20:4) mole % over baseline values following culture with FGF-1 and FGF-2, respectively. Unfractionated analysis on kidney and liver extracts from 4-6 week MRL lpr/lpr, 16-20 week lpr and 12-20 week MRL +/-/+/- mice demonstrated no significant intrastrain fatty acid differences. Higher levels of 20:4 in 4-6 week lpr mice were noted compared to 16-20 week lpr or +/+ mice in kidney, and liver samples (P < 0.05). It is possible that membrane changes precipitated by microenvironmental cytokine concentrations may contribute to the expression of autoimmune disease in this model.
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PMID:Environmental influences on fatty acid composition of membranes from autoimmune MRL lpr/lpr mice. 880 29

Many drug discovery efforts are focused on finding candidates that alter gene expression of the cytokines involved in inflammation, allergy, and cell-mediated immunity. Current methods used to evaluate gene expression such as northern blot and RT-PCR are laborious, time-consuming, expensive, and are not conducive to high throughput screening. High Performance Signal Amplification (HPSA( trade mark )) gene expression assays quantitate mRNA targets directly from cell lysate samples using DNA probe hybridization and fluorescent signal amplification. The assay format eliminates the need for RNA purification prior to testing and does not involve target amplification. The 96 or 384-well microplate formats allow the method to be run manually, by a workstation approach, or with full automation. Cellular mRNA levels are quantitated relative to a standard curve comprised of highly purified in vitro RNA calibrators. The analytical sensitivity is in the low attomole (10(-18) mole) range. This technique was used to monitor the transcription patterns of mRNA encoding TNF-alpha, IL-1beta, and Interferon-gamma in human cell lines or primary PBMC treated with inducers such as PMA, ionomycin, and endotoxin. The specificity, precision and reproducibility of the assay are sufficient to provide a reliable screening system. The HPSA gene expression assay system offers a rapid and convenient alternative to more cumbersome, expensive methods.
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PMID:Rapid assays for quantitating cytokine gene expression without target amplification. 1276 72

JWA, a newly identified novel microtubule-associated protein (MAP), was recently demonstrated to be indispensable for the rearrangement of actin cytoskeleton and activation of MAPK cascades induced by arsenic trioxide (As(2)O(3)) and phorbol ester (PMA). JWA depletion blocked the inhibitory effect of As(2)O(3) on HeLa cell migration, but enhanced cell migration after PMA treatment. As cancer cell migration is a hallmark of tumor metastasis and the functional role of JWA in cancer metastasis is not understood, here we show that JWA has an important role in melanoma metastasis. Our data demonstrated that JWA knockdown increased the adhesion and invasion abilities of melanoma cells. Furthermore, JWA knockdown in B16-F10 and A375 melanoma cells significantly promoted the formation and growth of metastatic colonies in vivo. Moreover, in the tumor biopsies from human melanoma patients, JWA expression was significantly decreased in malignant melanoma compared with normal nevi. In addition, we found that JWA knockdown could intensify tumor integrin alpha(V)beta(3) signaling by regulating nuclear factor Sp1. These findings suggest that JWA suppresses melanoma metastasis and may serve a potential therapeutic target for human melanoma.
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PMID:JWA regulates melanoma metastasis by integrin alphaVbeta3 signaling. 1994 36

Thermal field-flow fractionation coupled with online multiangle light scattering, differential refractive index and quasielastic light scattering (ThFFF-MALS/dRI/QELS) was used to simultaneously determine the molecular weight (MW) and composition of polystyrene-poly(n-butyl acrylate) (PS-PBA) and polystyrene-poly(methyl acrylate) (PS-PMA) copolymers. The online measurement of the normal diffusion coefficient (D) by QELS allowed calculation of the copolymer thermal diffusion coefficient (D(T)) of sample components as they eluted from the ThFFF channel. DT was found to be independent of MW for copolymers with similar compositions and dependent on composition for copolymers with similar MW in a non-selective solvent. By using a solvent that is non-selective to both blocks of the copolymer, it was possible to establish a universal calibration plot of DT versus mole fraction of one of the monomer chemistries comprising the copolymer. PS-PBA and PS-PMA linear diblock polymers were determined to vary in composition from 100/0 to 20/80 wt% PS/acrylate and ranged in MWs between 30 and 360 kDa. The analysis of a PS-PBA miktoarm star copolymer revealed a polydisperse material with a weight percent PBA of 50-75% and MW ranging from 100 to 900 kDa. The presented ThFFF-MALS/dRI/QELS method allowed rapid characterization of polymers with MW and chemical distributions in a single analysis.
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PMID:Composition and molecular weight analysis of styrene-acrylic copolymers using thermal field-flow fractionation. 2185 81

Platelet-activating factor-receptor (PAF-R) agonists are pleiotropic lipid factors that influence multiple biological processes, including the induction and resolution of inflammation as well as immunosuppression. PAF-R agonists have been shown to modulate tumorigenesis and/or tumor growth in various skin cancer models by suppressing either cutaneous inflammation and/or anti-tumoral adaptive immunity. We have previously shown that a chronic systemic PAF-R agonist administration of mice enhances the growth of subcutaneously implanted melanoma tumors. Conversely, chronic topical applications of a PAF-R agonist suppressed non-melanoma skin cancer (NMSC) in a topical chemical carcinogenesis model (dimethylbenz[a]anthracene/phorbol 12-myristate 13-acetate (DMBA/PMA)) in-part via anti-inflammatory effects. These results indicate that the context of PAF-R agonist exposure via either chronic cutaneous or systemic administration, result in seemingly disparate effects on tumor promotion. To further dissect the contextual role of PAF-R agonism on tumorigenesis, we chronically administered systemic PAF-R agonist, carbamoyl-PAF (CPAF) to mice under a cutaneous chemical carcinogenesis protocol, recently characterized to initiate both NMSC and melanocytic nevus formation that can progress to malignant melanoma. Our results showed that while systemic CPAF did not modulate melanocytic nevus formation, it enhanced the growth of NMSC tumors.
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PMID:Systemic Platelet-Activating Factor-Receptor Agonism Enhances Non-Melanoma Skin Cancer Growth. 3031 74