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

In primary cultures of rat pituitary cells, inhibin and follistatin reduce steady state levels of FSH beta mRNA to less than 10% of control within 4-6 h, while activin increases this mRNA 2- to 3-fold after 2-4 h of treatment. The effects of these three gonadal polypeptide hormones on the LH beta and common alpha-subunit mRNAs are more gradual and of lesser magnitude. The present study was designed to determine whether inhibin, activin, and/or follistatin act at the posttranscriptional level by altering the stability of the gonadotropin subunit mRNAs. To determine the decay rates of FSH beta, LH beta, and alpha-subunit mRNAs, primary pituitary cell cultures were treated for 1-24 h with either of two transcriptional inhibitors, actinomycin-D or 5,6-dichloro-1-beta-ribofuranosyl benzimidazole (DRB), in the presence or absence of recombinant human inhibin-A, recombinant human activin-A, or purified bovine follistatin. The decay of preexisting gonadotropin subunit mRNAs was followed by Northern blot analysis. Levels of LH beta and alpha-subunit mRNAs remained constant or increased during the 24-h exposure to transcriptional inhibitors; therefore, it was not possible to calculate their half-lives. The stability of these mRNAs was not altered by inhibin, activin, or follistatin. In contrast, FSH beta mRNA turned over rapidly: the estimated half-life was 2.6 +/- 0.19 h (mean +/- SEM of eight determinations) after actinomycin-D treatment and 1.9 +/- 0.14 h (mean +/- SEM of 12 determinations) after DRB treatment. When new RNA synthesis was blocked by either actinomycin-D or DRB, there were no significant effects of inhibin, activin, or follistatin on the stability of FSH beta mRNA (n = 2-4 for each hormone). The decay of FSH beta mRNA in the presence of inhibin or follistatin alone, however, was even more rapid than that determined after the administration of transcriptional inhibitors (P < 0.005). After an initial lag of 1-2 h, the half-life of FSH beta mRNA was 0.88 +/- 0.15 h (n = 4) or 0.62 +/- 0.11 h (n = 3), in the presence of inhibin or follistatin, respectively. The most likely interpretation of these results is that inhibin/follistatin reduces steady state levels of FSH beta mRNA by inducing a labile protein that accelerates the degradation of this mRNA species, and the synthesis of this protein is blocked by actinomycin-D or DRB treatment. It is not clear at present whether inhibin, follistatin, and activin have additional effects on transcription of the gonadotropin subunit genes.
Mol Endocrinol 1993 May
PMID:Decay of follicle-stimulating hormone-beta messenger RNA in the presence of transcriptional inhibitors and/or inhibin, activin, or follistatin. 768 52

We studied the differential expression of cellular adhesion molecules on the surface of purified human eosinophils and neutrophils caused by ex vivo activation with platelet-activating factor (PAF), formylmethionylleucylphenylalanine (FMLP), or recombinant human interleukin-5 (IL-5). PAF (10(-7) M) caused a 42.8 +/- 5.7% (mean +/- SEM) increase in Mac-1 expression in eosinophils (P < 0.01) and a 34.6 +/- 9.2% increase in Mac-1 expression in neutrophils (P < 0.05). PAF also caused a decrease in L-selectin expression in eosinophils (-37.0 +/- 8.1%, P < 0.001) and neutrophils (-14.1 +/- 3.2%, P < 0.05). FMLP (10(-6) M) caused a similar increase in Mac-1 expression in both eosinophils (P < 0.001 versus controls) and neutrophils (P < 0.01) and a comparable decrease in L-selectin expression in both eosinophils and neutrophils (P < 0.01). In contrast to the effects of PAF and FMLP, IL-5 affected selectively the surface expression of adhesion molecules in eosinophils but not neutrophils. Expression of Mac-1 increased by 44.3 +/- 7.5% in eosinophils (P < 0.001 versus controls) and by 0.7 +/- 1.2% in neutrophils (P = NS versus controls) after exposure to 10(-9) M IL-5. IL-5 also caused a 49.5 +/- 4.2% decrease in eosinophil L-selectin expression (P < 0.001) but had no effect on L-selectin expression in neutrophils. Eosinophil VLA-4 expression was not altered by any stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1993 Jun
PMID:Selective regulation of expression of surface adhesion molecules Mac-1, L-selectin, and VLA-4 on human eosinophils and neutrophils. 768 61

We are interested in the mechanisms of ozone-induced lung effects after short-term exposure and the relationship with subsequent pulmonary inflammation and disease. Our hypothesis is that ozone, as a powerful oxidant, will diminish the activity of neutral endopeptidase (NEP) in the airways of humans with resulting increased concentrations of neuropeptides such as substance P (SP). We have exposed seven (two women, five men) healthy, nonsmoking individuals (22 to 30 yr of age) to filtered air and ozone (0.25 ppm) for 1 h in an environmental chamber during heavy exercise. Bronchoscopy with airway lavage (AL) and bronchoalveolar lavage (BAL) was performed immediately after ozone exposure. The lavage samples were analyzed by enzyme immunoassay for SP and 8-epi-prostaglandin F2 alpha (8-epi-PGF2 alpha) (a marker for oxidative free radical reaction) and by radioimmunoassay for complement fragments. FEV1 had declined 12.4 +/- 1.9% (mean +/- SEM) as a result of ozone exposure. The AL concentration for SP and 8-epi-PGF2 alpha and BAL concentration of C3a after ozone exposure were significantly higher than after the filtered air exposure (P < 0.05). There was a significant correlation between SP and 8-epi-PGF2 alpha concentrations in the AL fluid (r2 = 0.89 and P < 0.05). There were no changes in C5a in either compartment or any of the mediators in the plasma samples. These results extend previous results from animal studies suggesting that ozone's mechanism of action is through an oxidative reaction resulting in a decreased activity of NEP in the airways with a subsequent increase in the concentration and activity of SP.
Am J Respir Cell Mol Biol 1993 Nov
PMID:Ozone-induced increases in substance P and 8-epi-prostaglandin F2 alpha in the airways of human subjects. 769 98

The early onset of proTRH gene expression in anterior pituitary (AP) cells in culture and its regulation by dexamethasone (DEX) were investigated. AP cells derived from 15-day-old rats were cultured for up to 4 days in the presence or absence of 10(-7) M DEX. TRH peptide levels, which could be detected only after 3 days of culture in control cells, were detectable after 1 day in DEX-treated cells. Levels rose from undetectable (< 35 fmol/well/0.2 x 10(6) cells) to 121 +/- 11 fmol/well in control cells and from 59 +/- 3 to 2978 +/- 88 fmol/well in DEX-treated cells (Day 1 to Day 4; means +/- SEM, n = 6). ProTRH mRNA levels as analyzed by in situ hybridization showed an excellent correlation with TRH peptide levels: mRNA was already detectable on Day 1 in DEX-treated cells and on Days 2-3 in control cells. DEX stimulated proTRH mRNA levels as determined by Northern blot analysis within 4 h. The half-life of proTRH mRNA was calculated based on a first-order decay model by measuring mRNA levels after addition of 5 micrograms/ml actinomycin D with or without DEX. The t1/2 of proTRH mRNA in control cells was 13.1 +/- 2.8 h and was not influenced by DEX treatment (12.5 +/- 2.8 h). Since DEX stimulated proTRH mRNA levels acutely without any increase in mRNA stability, we propose that DEX expedites proTRH gene expression in our AP cell culture system by acting at the transcriptional level.
Mol Cell Neurosci 1994 Dec
PMID:Onset of pro-thyrotropin-releasing hormone gene expression in cultured rat anterior pituitary cells is expedited by dexamethasone. 770 42

Integrative gene therapy typically requires dividing cells. This requirement has been perceived as an impediment for gene transfer to mature, uninjured airways where proliferation rates are very low. In diseases such as cystic fibrosis (CF) that may be candidates for integrative gene therapy, airway cell turnover is not known but may be increased as a result of chronic inflammation. To determine if cells in airway surface epithelium and submucosal glands of CF patients proliferate at an increased rate, paraffin sections of bronchial segments removed from CF patients (n = 6) at the time of lung transplantation or rapid autopsy and from non-CF patients (n = 4) undergoing lung resection or transplantation were immunostained with PC10, a monoclonal antibody to proliferating cell nuclear antigen (PCNA), a marker of proliferating cells. The PCNA index (percentage of nuclei immunostaining for PCNA) in CF bronchial surface epithelium was 17.0 +/- 4.6% (mean +/- SEM), substantially greater than in non-CF airways (less than 0.2%). Within submucosal glands, PCNA-positive cells were more prevalent in the collecting ducts of CF patients than in those of normal subjects, but only rare mucous or serous cells were PCNA positive. These studies show that airway epithelial cell proliferation rates can be very high in inflamed CF airways. This prevalence of proliferating cells suggests that CF airway epithelium and submucosal gland ducts may be amenable to gene transfer using vectors, such as retroviruses, that require cell replication for stable integrative expression. Further studies are needed to evaluate cell proliferation in CF airways with less extensive airway injury.
Am J Respir Cell Mol Biol 1995 Jun
PMID:Cell proliferation in bronchial epithelium and submucosal glands of cystic fibrosis patients. 776 25

We have studied the time course of hepatic and renal microsomal glucose-6 phosphatase (Glc-6Pase) during long-term fasting in the rat. Liver microsomal Glc-6Pase increases up to 48 hr and significantly decreases after 48 hr of fasting. The following activities were determined at 0, 24, 48, 72 and 96 hr: 0.31 +/- 0.02; 0.50 +/- 0.02; 0.54 +/- 0.03; 0.44 +/- 0.03; 0.44 +/- 0.01 mumol min-1 mg protein-1, respectively (all values are means +/- SEM, n = 6). Concomitantly, kidney microsomal Glc-6Pase progressively increases throughout the fast (Vm = 0.21 +/- 0.01; 0.26 +/- 0.004; 0.30 +/- 0.01; 0.37 +/- 0.02; 0.40 +/- 0.01 mumol min-1 mg protein-1, from 0 to 96 hr, respectively). These data suggest that the differential expression of Glc-6Pase activity in the liver and the kidney during long-term fasting could have an important role in the shift from a principally hepatic gluconeogenesis to a hepatic and renal gluconeogenesis.
Comp Biochem Physiol B Biochem Mol Biol 1994 Sep
PMID:Differential time course of liver and kidney glucose-6 phosphatase activity during fasting in rats. 784 31

After feeding rats a vitamin B-6-deficient diet, we observed a decrease in pyridoxal 5'-phosphate concentrations in intestinal mucosa cells to 32 and 48% of control in cytoplasm and cell nuclei, respectively. Correlation analysis suggested that there were two pyridoxal 5'-phosphate pools in the nuclei: a "mobile" pool (equivalent to about 5% the concentration of the cytoplasmic pyridoxal 5'-phosphate), and a "stable" pool, which was independent of cytoplasmic fluctuations of pyridoxal 5'-phosphate (about 9 pmol pyridoxal 5'-phosphate/mg DNA). Reduction in pyridoxal 5'-phosphate content in the cells of vitamin B-6-deficient animals was accompanied by a substantial increase in 1,25-dihydroxyvitamin D-receptor ligand concentration in the cell nuclei (76.6 +/- 19.7 vs 762 +/- 291 fmol/mg DNA, mean +/- SEM). The degree of 1,25-dihydroxyvitamin D accumulation in the nuclei appeared to be an exponential function of the "mobile" nuclear pyridoxal 5'-phosphate concentration. Semilogarithmic transformation of the data yielded a straight line, representing an inverse correlation between the cytoplasm-related nuclear pool of pyridoxal 5'-phosphate and the logarithm of the 1,25-dihydroxyvitamin D concentration in the nuclei (r = -0.95). These data suggest that pyridoxal 5'-phosphate may be related to 1,25-dihydroxyvitamin D retention in the nuclei, possibly through interaction of the pyridoxal 5'-phosphate with the vitamin D receptor protein in the nuclei.
J Steroid Biochem Mol Biol 1994 Sep
PMID:Pyridoxal 5'-phosphate related changes in retention of 1,25-dihydroxy vitamin D-receptor ligands in rat intestinal mucosa cell nuclei. 791 14

Specific binding sites for ANF have been identified on human platelets. To determine maximal binding (Bmax) and dissociation constant (Kd), we adapted the only original method by developing a specific sequence of platelet preparation. From venous blood collected on citrated anticoagulant, platelets were prepared by successive centrifugations at 20 degrees C (blood centrifugated at 1500 rpm for 10 min., supernatant centrifugated at 3000 rpm for 1 min., supernatant centrifugated at 2800 rpm for 10 min, the inner platelet-rich layer resuspended in citrated solution) and aliquoted (200 microliters at 5.10(5) platelets/microliters). Competition experiments [incubation of platelets with fixed concentration (20-25 pM) of labeledhuman ANF (125Ih ANF) and increasing concentrations (10(-12) to 10(-6) pM) of unlabeled hANF] led to the drawing of a mean displacement curve (n = 8), usable as reference, and to verification of the specificity of binding assay (cross-reactivity with ratANF, no cross-reactivity with arginine-vasopressine). From saturation experiments [incubation of platelets with increasing concentrations (3.5 to 63.7 pM) of labeled hANF and with (10(-8) M) or without unlabeled hANF], we determined (n = 11): Bmax (m +/- SEM) = 4.5 +/- 0.7 pM or 5.4 +/- 0.8 sites per cell and Kd (m +/- SEM) = 10.84 +/- 1.70 pM.
Cell Mol Biol (Noisy-le-grand) 1994 May
PMID:Atrial natriuretic factor receptors on human platelets. 792 Jan 77

Several functions of alveolar macrophages (AM) are modified by cigarette smoking. AM are the first line of defense in bronchoalveolar spaces and could be depressed in their cytotoxicity to tumor cells in smokers. An assay using A549 cells (human lung adenocarcinoma) as target cells was performed to assess cytostasis mediated by AM and their supernatants (SN) from healthy smokers (n = 8) and nonsmokers (n = 6). Contact-mediated cytostasis was decreased in AM of smokers (n = 8) relative to nonsmokers (n = 6) (22.9 +/- 5.7% versus 42.7 +/- 6.0% [+/- SEM], P < 0.04) and increased after lipopolysaccharide (LPS) stimulation in both groups (34.5 +/- 5.3% versus 46.8 +/- 5.2%, NS). Cytostasis induced by SN from nonstimulated AM was low in both groups and was still lower in smokers after LPS exposure (19.3 +/- 4.5% versus 34.5 +/- 4.8%, P < 0.04). Among cytotoxic factors produced by macrophages, interleukin (IL)-1 beta, IL-6, and tumor necrosis factor alpha (TNF alpha) may play an important role in cytostasis. Recombinant human (rH) IL-1 beta and rHTNF alpha had a moderate cytostatic activity, which was additive, whereas rHIL-6 had no significant activity on A549 cells. Bioactive IL-1 beta, IL-6, and TNF alpha were therefore measured in macrophage SN. Their levels tended to be lower in smokers than in nonsmokers and were much increased after LPS stimulation. Levels of the three cytokines were also found to correlate with each other; furthermore, a good correlation between cytokine levels in SN and cytostasis was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1994 Nov
PMID:Cytostatic activity of alveolar macrophages from smokers and nonsmokers: role of interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha. 794 92

We investigated the production of leukemia inhibitory factor (LIF) by human carcinoma cell lines. LIF mRNA was detected by Northern blot analysis in all 24 carcinoma cell lines of the lung, breast, stomach, colon, liver, gallbladder, pancreas and melanocytes. Seventeen of them (70.8%) secreted LIF in the culture supernatant (range: 40.4-3990.3 pg/ml, mean +/- SEM: 611.8 +/- 262.9 pg/ml). Biologic activity of LIF was confirmed in the culture supernatant of carcinoma cell lines by the MTT assay using M1 cells. The present results showed that human carcinoma cell lines are constitutively producing biologically active LIF. The possible biological significance of LIF produced by cancer cells is discussed.
Res Commun Mol Pathol Pharmacol 1994 Aug
PMID:Human carcinoma cell lines produce biologically active leukemia inhibitory factor (LIF). 799 57


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