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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Subjects with elevated serum estrogen concentrations, such as those who are pregnant or ingesting estrogen-containing contraceptive medication, may develop increased skin pigmentation. As little information is available on the mechanism(s) underlying this relationship, the in vitro effects of estrogens on melanocytes cultured from normal human skin were examined. Physiological concentrations of 17 beta-estradiol (10(-11) to 10(-9) M) significantly increased the activity of tyrosinase in melanocytes from 15 of 23 subjects. The observed increases ranged from 1.2- to 2.4-fold. Melanin synthesis, which correlated with tyrosinase activity (r = 0.98, P < 0.001) was increased to a similar extent. Melanin extrusion was also increased by 17 beta-estradiol (10(-9) M). The estrogens, estriol (10(-9) M) and estrone (10(-9) M) stimulated tyrosinase activity and melanin extrusion to a lesser extent than 17 beta-estradiol. The analogue 17 alpha-estradiol (10(-9) M) was shown to have effects on melanocyte tyrosinase activity and melanin extrusion that were equivalent to those of 17 beta-estradiol. The pure estrogen antagonist ICI 164384 (10(-6) M) also stimulated tyrosinase activity. Cycloheximide (50 micrograms/ml) inhibited 17 beta-estradiol-induced tyrosinase stimulation (P < 0.001). These results indicate that several aspects of melanocyte function respond directly to estrogenic stimulation. The equivalent effects of the 17 alpha-analogue and a "pure" anti-estrogen suggest that the 17 beta-estradiol response may be mediated through a non-classical mechanism which is similar to that described in other tissues of neural crest origin.
J Steroid Biochem Mol Biol 1994 May
PMID:Effects of estrogens on human melanocytes in vitro. 800 45

Histamine is a major mediator of the mast cells that are present between epithelial cells in asthma. In asthma, there is an increased expression of ICAM-1 and HLA-DR and an increased spontaneous release of fibronectin. The effect of histamine was tested on bronchial epithelial cells obtained by bronchial brushing from 22 nonasthmatic subjects. The activation of epithelial cells was assessed by immunocytochemical analysis of the expression of membrane markers (ICAM-1 and HLA-DR) using the alkaline phosphatase-anti-alkaline phosphatase method and the release of fibronectin (enzyme immunoassay). Time-response (three experiments) and dose-response (six experiments) curves showed that the maximal effect was obtained after an incubation time of 24 h and a dose of 1 microM of histamine. For this time course and concentration, there was a highly significant increase in the number of cells expressing ICAM-1 (before histamine: 10 +/- 11%; after histamine: 32 +/- 20%; P < 0.001) and HLA-DR (before histamine: 8 +/- 7%; after histamine: 23 +/- 20%; P < 0.001) and in the release of fibronectin (before histamine: 30 +/- 20 ng/10(5) viable cells; after histamine: 61 +/- 35 ng/10(5) viable cells; P < 0.003). Cycloheximide blocked these effects, suggesting that histamine requires protein synthesis for its action. Pyrilamine (H1-blocker) and ranitidine (H2-blocker) at a concentration of 10 microM decreased the effect of histamine. However, there was no additive effect when both antagonists were added. This study suggests that mast cells present in the airways have a role in the activation of epithelial cells.
Am J Respir Cell Mol Biol 1993 Oct
PMID:Activation by histamine of bronchial epithelial cells from nonasthmatic subjects. 810 36

Incubation of MCF-7 cells with estradiol (E2) down-regulates estrogen receptor (ER) resulting in a progressive reduction of the capacity of cells to concentrate selectively [3H]E2. Scatchard plot analysis failed to detect any transformation of residual receptors into peptides of lower binding affinity. [3H]Estrone gave an identical ER disappearance pattern with an ER half-life comprised between 2 and 3 h. A similar value was established by incubating the cells with [3H]tamoxifenaziridine ([3H]TAZ) for 1 h before the addition of excessive unlabeled E2 which induced ER-down regulation and impeded any further labeling of the residual receptors. Submission of the [3H]TAZ labeled cell extracts to SDS-PAGE revealed no progressive emergence of low molecular weight cleavage products of the receptor (< 67 kDa). Two inhibitors of protein kinases, H-7 at 40 microM and H-89 at 20 microM, failed to block the E2-induced ER down-regulation. On the contrary, the protein phosphatases 1 and 2A inhibitor, okadaic acid, was effective with concentrations higher than 0.1 microM indicating that a dephosphorylation mechanism was involved in this phenomenon. Cycloheximide (CHX) also significantly reduced the receptor decrease at concentrations higher than 1 microM. G-C specific intercalating agents [actinomycin D (AMD) and chromomycin A3 at 1 microM] also prevented ER disappearance; ethidium bromide (EB) and quinacrine were ineffective. AMD and CHX operated immediately after their addition to the medium indicating an inhibitory action on the synthesis of an RNA and/or a peptide with high turnover rate involved in ER decline. Moreover, AMD produced its suppressive effects under conditions impeding any labeling of newly synthetized receptors (i.e. [3H]TAZ with an excess of unlabeled E2) rejecting the possibility of an increasing ER production which may partially hamper its disappearance. Finally, E2-induced ER mRNA down-regulation was similarly abolished by AMD while EB and CHX were devoid of effect.
J Steroid Biochem Mol Biol 1994 Mar
PMID:Estradiol-induced down-regulation of estrogen receptor. Effect of various modulators of protein synthesis and expression. 814 11

Little is known about how mRNA stability is regulated in higher plants. The SAURs (Small Auxin-Up RNAs) are a family of highly unstable mRNAs in soybean that rapidly increase in abundance after excised organs are treated with the plant hormone auxin. The SAURs are also induced by protein synthesis inhibitors, including cycloheximide, in the absence of auxin treatment and are superinduced when organs are treated with cycloheximide plus auxin. While the induction of SAURs is transcriptionally regulated by auxin, the induction by cycloheximide is posttranscriptional. Cycloheximide as well as other protein synthesis inhibitors appear to induce SAUR accumulation by increasing the stabilities of these mRNAs. To determine whether the 5'-untranslated region, the 3'-untranslated region, or the open reading frame of these unstable mRNAs is responsible for the cycloheximide inducibility, we have used chimeric genes in transgenic tobacco plants to test each of these mRNA regions. Our results show that the SAUR open reading frame within a chimeric mRNA confers cycloheximide inducibility in transgenic tobacco plants whereas chimeric mRNAs containing the SAUR 5'-untranslated region or 3'-untranslated region as isolated elements or in combination are not induced by cycloheximide. These results suggest that the SAUR open reading frame contains sequence elements that are involved in the stability of these mRNAs.
Plant Mol Biol 1994 Mar
PMID:The soybean SAUR open reading frame contains a cis element responsible for cycloheximide-induced mRNA accumulation. 819 96

alpha 1-Adrenergic receptors play important roles in mediating a wide range of important cellular responses; regulation of expression of these receptors may have pathophysiological significance in diseases such as hypertension. In order to pursue understanding of mechanisms involved in the regulation of expression of alpha 1 receptors, the effects of protein synthesis inhibitor cycloheximide on alpha 1B receptor gene expression were examined in DDT1 MF-2 smooth muscle cells. Cycloheximide markedly induced accumulation of the alpha 1B receptor mRNAs in a concentration- and time-dependent manner as detected by Northern blotting assays. The increased accumulation of alpha 1B receptor mRNA could be detected at 1 hr (1.7 +/- 0.2-fold) and the maximal accumulation occurred at 6 hr (5.4 +/- 0.3-fold, p < 0.01). Nuclear runoff assays reveal that cycloheximide markedly increased the transcriptional rate of the alpha 1B receptor gene. The stability of alpha 1B receptor mRNAs measured by RNase protection assays was essentially unchanged by cycloheximide. Incubation of DDT1 MF-2 cells with two additional protein synthesis inhibitors, anisomycin and emetine, had similar effects to those of cycloheximide. However, a further inhibitor, puromycin, did not induce alpha 1B receptor mRNAs when protein synthesis was almost completely inhibited. Furthermore, puromycin did not inhibit the capacity of cycloheximide to induce transcription of the alpha 1B receptor gene. These observations suggest that cycloheximide induces alpha 1B receptor gene expression through direct activation of gene transcription rather than inhibition of protein synthesis.
Mol Pharmacol 1993 Dec
PMID:Cycloheximide induces the alpha 1B adrenergic receptor gene by activation of transcription in DDT1 MF-2 smooth muscle cells. 826 46

During left ventricular hypertrophy, brain natriuretic peptide (BNP) and atrial natriuretic factor (ANF) mRNA levels increase, possibly due to stretch-induced activation of protein kinase C. Phorbol ester treatment of primary cultures of neonatal rat ventricular cardiocytes represents an in vitro model of hypertrophic cell growth and has previously been shown to stimulate ANF synthesis and secretion. Using this model, we studied the synthesis and secretion of BNP to determine whether its regulation in cardiac cells is similar to ANF. Addition of 10(-7) M phorbol 12-myristate 13-acetate (PMA) resulted in a 3- to 4-fold increase in immunoreactive BNP (irBNP) secretion 24-48 h after treatment. Over a concentration range of 10(-8)-10(-6) M, PMA increased irBNP secretion to equivalent levels. Another phorbol ester agonist, phorbol 12,13-didecanoate, stimulated irBNP secretion, while the inactive analog 4 alpha-phorbol 12,13-didecanoate had no effect. Inhibition of protein kinase C (PKC) with 10(-8) M staurosporine decreased basal secretion of irBNP 60% and prevented PMA induction of irBNP, whereas both stimulated and basal secretion of ANF were minimally affected. BNP mRNA increased 6-fold by 3 h of PMA treatment and remained elevated above control levels for 48 h. Staurosporine prevented the increase in BNP mRNA. To determine whether PKC or a PKC-dependent pathway was involved in persistent stimulation of BNP and ANF in cells chronically treated with PMA, ventricular cardiocytes were treated with PMA for 24 h, followed by PMA plus 10(-8) M staurosporine for 24 h. BNP mRNA was reduced to control levels, while ANF mRNA was reduced by an average of 20%. To test whether mRNA stability was involved in the differential effect of chronic phorbol ester treatment, cardiocytes were treated with the protein synthesis inhibitor cycloheximide (20 micrograms/ml). BNP mRNA levels were stimulated as early as 30 min after treatment, but ANF mRNA remained unaffected. Cycloheximide also potentiated PMA's effect on BNP mRNA after 1.5, 9.5, and 24 h of treatment. To test whether a transcriptional mechanism was involved in the stimulation of BNP mRNA by PMA, cells were treated with the inhibitor actinomycin D (5 micrograms/ml) for 24 h in the presence of PMA. Actinomycin D reduced the stimulatory effect of PMA on BNP mRNA.(ABSTRACT TRUNCATED AT 400 WORDS)
Mol Endocrinol 1993 Oct
PMID:Phorbol ester stimulates the synthesis and secretion of brain natriuretic peptide from neonatal rat ventricular cardiocytes: a comparison with the regulation of atrial natriuretic factor. 826 60

Treatment of MCF-7 cells with 1 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 1 nM [3H]17 beta-estradiol resulted in decreased radiolabeled nuclear estrogen receptor (ER) levels as determined by velocity sedimentation analysis. In parallel studies, nuclear extracts from TCDD-treated cells also exhibited decreased binding to a consensus 32P-genomic estrogen responsive element (ERE) as determined in a gel mobility shift assay. Time-course studies showed that the decreases in nuclear ER and ER-ERE binding in TCDD-treated cells were observed within 1 to 3 h after treatment, respectively, and persisted for up to 24 h. Cycloheximide (10 microM) did not affect the TCDD-mediated response, whereas 1 microM alpha-naphthoflavone, an aryl hydrocarbon (Ah) receptor antagonist, partially blocked downregulation of nuclear ER binding by TCDD. TCDD did not significantly affect steady state ER mRNA levels as determined by Northern analysis or the rate of ER gene transcription in a nuclear run-on assay. These results suggest that the TCDD-mediated decrease in nuclear ER levels is an Ah receptor-mediated response which occurs at the translational or post-translational level.
Mol Cell Endocrinol 1993 Oct
PMID:Mechanism of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated decrease of the nuclear estrogen receptor in MCF-7 human breast cancer cells. 827 31

cAMP participates in the regulation of endogenous hypothalamic and placental CRF by increasing levels of both peptide secretion and mRNA expression. In previous studies we have shown that stimulation of the protein kinase A-dependent pathway by cAMP analogues or forskolin produced a dose-dependent increase in levels of CRF mRNA when the intact hCRF gene was stably transfected and expressed in the mouse corticotroph AtT20 cell line. In the present study, we explored the mechanism of the cAMP-dependent increase in CRF gene expression in the stably transfected AtT20 cell line using pharmacologic, slot-blot, and RNase mapping methodologies. Following incubation with cAMP, there was a rapid increase in CRF mRNA which was completely blocked by pre-treatment with actinomycin D, an inhibitor of transcription. Cycloheximide, an inhibitor of protein synthesis, produced an independent increase in CRF mRNA, but did not change the relative induction of CRF mRNA produced by cAMP. Solution hybridization studies using intron- and exon-specific hCRF probes demonstrated a rapid rise in nuclear CRF hnRNA, which was apparent within 15 min of cAMP incubation and preceded the rise in cytoplasmic CRF mRNA. RNase mapping studies demonstrated that CRF transcription was initiated at discrete promoter sites in CRF-AtT20 cells, and that this pattern of promoter utilization was similar to that observed in mRNA derived from sites of endogenous CRF expression, human placenta and human hepatoma NPLC cell line. Treatment with cAMP selectively increased CRF mRNA transcripts initiated at the proximal promoter site, but had little or no effect on transcripts initiated at the distal promoters. We conclude that cAMP effects on CRF gene expression occur rapidly, do not require new protein synthesis, and are initiated within the nuclear compartment, consistent with a direct effect on CRF gene transcription. This effect is mediated predominantly through the proximal promoter element, while more distal promoters are less sensitive to transcriptional activation by cAMP.
Mol Cell Endocrinol 1993 Oct
PMID:Transcriptional regulation of human corticotropin releasing factor gene expression by cyclic adenosine 3',5'-monophosphate: differential effects at proximal and distal promoter elements. 827 45

Connective tissue growth factor (CTGF) is a cysteine-rich peptide that exhibits platelet-derived growth factor (PDGF)-like biological and immunological activities. CTGF is a member of a family of peptides that include serum-induced immediate early gene products, a v-src-induced peptide, and a putative avian transforming gene, nov. In the present study, we demonstrate that human foreskin fibroblasts produce high levels of CTGF mRNA and protein after activation with transforming growth factor beta (TGF-beta) but not other growth factors including PDGF, epidermal growth factor, and basic fibroblast growth factor. Because of the high level selective induction of CTGF by TGF-beta, it appears that CTGF is a major autocrine growth factor produced by TGF-beta-treated human skin fibroblasts. Cycloheximide did not block the large TGF-beta stimulation of CTGF gene expression, indicating that it is directly regulated by TGF-beta. Similar regulatory mechanisms appear to function in vivo during wound repair where there is a coordinate expression of TGF-beta 1 before CTGF in regenerating tissue, suggesting a cascade process for control of tissue regeneration and repair.
Mol Biol Cell 1993 Jun
PMID:Regulation of connective tissue growth factor gene expression in human skin fibroblasts and during wound repair. 837 72

Glucocorticoids increase expression of the genes for the pulmonary surfactant-associated proteins SP-B and SP-C in fetal lung both in vivo and in vitro. To examine the mechanism of these effects, we studied induction of SP-B and SP-C mRNAs in human fetal lung cultured as explants. Both mRNA levels rose rapidly in response to 100 nM dexamethasone (Dex), with a faster response for SP-B: maximal levels of induction were achieved in < or = 12 h for SP-B (3.5-fold versus control) versus approximately 24 h for SP-C mRNA (35-fold versus control). Cycloheximide (2.5 micrograms/ml) did not affect glucocorticoid induction of SP-B mRNA but markedly decreased induction of SP-C mRNA. In control cultures, cycloheximide did not significantly reduce levels of either transcript. In nuclear run-on assays, Dex increased the rate of gene transcription for both SP-B (2.8 +/- 0.3-fold versus control, n = 4) and SP-C (10- to 30-fold). Using actinomycin D to assess mRNA stability, the t1/2 of SP-B mRNA was increased from 7.5 +/- 0.4 h to 18.8 +/- 2.9 h by Dex treatment (P < 0.05), whereas the t1/2 of SP-C mRNA was not affected (9.3 +/- 1.7 h versus 8.1 +/- 1.2 h; NS). A similar increase in SP-B mRNA t1/2 with Dex (from 6 h to 19 h) was observed in label-chase studies with [3H]uridine. We conclude that glucocorticoids regulate the hydrophobic surfactant proteins of alveolar type II cells by different mechanisms: induction of SP-B is a primary response and includes an increase in both transcription rate and mRNA stability, whereas induction of SP-C is a secondary process, requiring ongoing protein synthesis, involving increased transcription rate without a change in mRNA stability.
Am J Respir Cell Mol Biol 1993 Feb
PMID:Differential glucocorticoid regulation of the pulmonary hydrophobic surfactant proteins SP-B and SP-C. 842 12


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