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)

Nutrient interactions during intestinal digestion has been established in animals. The present study investigated the effect of different nutrients on intestinal dipeptidase, tripeptidase, carboxypeptidase (EC 3.4.12.-) and aminopeptidase N (ApN) (EC 3.4.11.2) activities in human fetuses and children. The effect of nutrients on isolated porcine kidney ApN was also studied. Sucrose, lactose and tributyrin had no effect on di-, tri-, and carboxypeptidase activities of mucosal homogenates, but tributyrin significantly (20-50%) inhibited both fetal and postnatal ApN activity in the small intestine and colon. The pH-independent inhibition of ApN is specific for tributyrin and to the product of its hydrolysis, butyric acid. Glycerol, triolein, and natural oils did not affect ApN activity. The inhibition of ApN by tributyrin was dose and time dependent and occurred in enterocyte brush border membranes as well as in the purified enzyme from porcine kidney. The kinetics of the purified ApN showed that the tributyrin effect is primarily competitive and associated mainly with an increase in K(m). These observations demonstrate the possibility of intestinal and kidney ApN regulation by lipids and products of their hydrolysis. We speculate that nutrient interactions arose quite early in the evolution and represent a mechanism for the regulation of food digestion.
Comp Biochem Physiol A Mol Integr Physiol 1999 Oct
PMID:Regulation of intestinal peptidases by nutrients in human fetuses and children. 1062 59

The role of melatonin in the regulation of human reproduction remains unclear. In the present study, we examined the influence of exogenous melatonin on pulsatile luteinizing hormone (LH), diurnal rhythm of testosterone, and endogenous melatonin profile in six healthy young adult males. To test the hypothesis that the effect of melatonin on LH or testosterone secretory patterns may be mediated through the benzodiazepine-(BNZ) gamma-amino-butyric acid (GABA) receptor complex, a benzodiazepine receptor antagonist (Flumazenil) was administered. The study design comprised four 10-h (4:00 PM-2:00 AM) testing periods. During each experimental period, subjects were given an oral dose of placebo, or 3 mg melatonin or 10 mg flumazenil, at 5:00 PM, in a randomized, double-blind, partially repeated Latin square design in the following combinations: placebo-placebo, placebo-melatonin, flumazenil-placebo, and flumazenil-melatonin. The following day, serum samples were obtained every 20 min between 4:00 PM and 2:00 AM in a controlled light-dark environment for the determination of LH and melatonin levels. Serum testosterone concentrations were determined every 20 min between 7:00 and 8:00 AM and 7:00 and 8:00 PM. A significant decrease in mean serum LH levels (p < 0.02) was observed in the melatonin-treated groups as compared with placebo-flumazenil groups. There was no change in LH pulse frequency, testosterone levels, or in melatonin onset time and amplitude. No additional effect of flumazenil on LH or testosterone levels was observed. These data indicate that an evening melatonin administration decreases the next-day LH secretion in normal adult males without altering testosterone levels or the endogenous nocturnal melatonin secretory pattern. This effect of melatonin is not mediated through the benzodiazepine-GABA receptor complex.
J Mol Neurosci 1999 Feb
PMID:Melatonin administered in the afternoon decreases next-day luteinizing hormone levels in men: lack of antagonism by flumazenil. 1063 72

A pilot phase II open study on 12 patients with thalassemia intermedia (7 men, 5 women; age 31 +/- 2.0 years SE) treated with oral isobutyramide, a derivative of butyric acid (150 mg/kg body wt/day), was performed in order to evaluate the effect of this compound in stimulating hemoglobin F (HbF) production. No patient underwent blood transfusion in the 1-year time frame prior to the study. Nine patients were splenectomized. Safety was monitored by clinical and laboratory tests. Efficacy was assessed in terms of the non-alpha/alpha globin chain biosynthetic ratio and the percentage increase of HbF. The study design consisted of a screening phase, a treatment phase of 28 days, and a posttreatment follow-up of 28 days. All patients completed the study. Compliance to treatment was 100%. No drug-related adverse event was recorded. We observed little or no increase in the non-alpha/alpha ratio in the majority of patients. Six patients showed a percentage increase of HbF at the end of treatment and in 5 of those 6 further increases at the end of the follow-up period were observed. The change in percentage of HbF over time was close to significance both in the treatment period (P = 0. 06) and in the follow-up period (P = 0.08). These results indicate that butyrate derivatives can stimulate fetal hemoglobin in patients with intermediate thalassemia. Testing of the effects of different schedules of administration of isobutyramide will be required in order to determine the optimal use of this compound in the treatment of the beta-thalassemia syndromes.
Blood Cells Mol Dis 2000 Feb
PMID:Oral isobutyramide therapy in patients with thalassemia intermedia: results of a phase II open study. 1077 82

The study of fluorescence energy transfer from the phenyl groups of the micellar triton X-100 (TX-100) to solubilised 1-pyrene butyric acid (PBA) has been carried out. Through the analysis of the donor fluorescence quenching energy transfer efficiency has been determined. The observed donor-acceptor separation suggests that pyrene molecules are distributed uniformly in the micellar core.
Spectrochim Acta A Mol Biomol Spectrosc 2000 Mar
PMID:Energy transfer in triton-X 100 micelles: a fluorescence study. 1079 53

Sodium butyrate enhances TNF-alpha-induced complement C3 secretion but suppresses TNF-alpha-induced factor B secretion in intestinal epithelial cells. To further evaluate the mechanism underlying these responses, we assessed the effects of trichostatin A, a compound structurally unrelated to butyrate and a potent inhibitor of histone deacetylase. The C3 and factor B secretion was evaluated by enzyme-linked immunosorbent assay (ELISA) and Northern blot, and the activation of transcription factor was assessed by an electrophoretic gel mobility shift assay (EMSA). Like sodium butyrate, trichostatin A enhanced TNF-alpha-induced C3 secretion, but suppressed TNF-alpha-induced factor B secretion. These effects were also observed at the level of mRNA. EMSAs indicated that trichostatin A weakly suppressed TNF-alpha-induced NF-kappaB and NF-IL6 activation. These observations differ from previous reports that sodium butyrate potently suppressed NF-kappaB activation but enhanced NF-IL6 activation. Trichostatin A modulated TNF-alpha-induced C3 and factor B secretion in a manner similar to that induced by sodium butyrate, suggesting that both sodium butyrate and trichostatin A exert certain counter-regulatory effects associated with histone hyperacetylation. However, it remains to be determined which factors other than histone acetylation are responsible for the counter-regulation of TNF-alpha-induced C3 and factor B gene expression.
Int J Mol Med 2000 Jul
PMID:Modulation of complement component (C3 and factor B) biosynthesis by a histone deacetylase inhibitor in human intestinal epithelial cells. 1085 Dec 66

Pivalyloxymethyl butyrate (AN9) is an anticancer derivative of butyric acid. In this study, doxorubicin (DXR) and AN9 synergistically inhibited the growth of lymphoma and lung carcinoma cells, whereas there was no synergy between AN9 and antimetabolites. AN9 did not affect the intracellular uptake of DXR. Among anthracyclines and their derivatives, the synergistic effect was prominent in compounds with a daunosamine moiety, suggesting that AN9 may affect the catabolism of these compounds. The degradation of DXR in the extract from AN9-treated cells was much less than that in extract from untreated cells. AN9 did not directly inhibit the enzyme activity but rather suppressed expression of the enzyme. With respect to the expression of drug resistance-related genes, there was no significant difference between untreated and AN9-treated cells. However, AN9 significantly down-regulated the levels NADPH-cytochrome P450 reductase and DT-diaphorase mRNA in the presence of DXR but not the level of xanthine oxidase mRNA. The enhancement of the sensitivity to anthracyclines was closely associated with the suppression of the mRNA expression.
Mol Pharmacol 2000 Jul
PMID:Anticancer derivative of butyric acid (Pivalyloxymethyl butyrate) specifically potentiates the cytotoxicity of doxorubicin and daunorubicin through the suppression of microsomal glycosidic activity. 1086 Sep 24

Domestic organic waste (DOW) was washed and dried to 85 % dryness by VAM (The Netherlands). This material contained 25.1 g glucose, 8.4 g xylose and 5.8 g other monosaccharides/100 g dry matter. Using Mansonite steam explosion and enzymatic hydrolysis, a hydrolysate containing 15.4 g glucose, 2.2 g xylose and 0.8 g other monosaccharides per l was made. Clostridium acetobutylicum DSM 1731 produced 1.5 and C. beijerinckii B-592 0.9 g/l ABE and Clostridium LMD 84.48 1.9 g/l IBE, respectively, from this hydrolysate without further supplementation. Incubation with 2 fold concentrated hydrolysate completely impaired ABE production. After removal of unspecific inhibiting components, the yield of ABE production by Clostridium acetobutylicum DSM 1731 increased about 3 fold as compared to the nontreated hydrolysate. From 4 fold concentrated, partially purified, hydrolysate containing 34.2 g glucose/l, ABE production was 9.3 g/l after 120 h as compared to 3.2 g ABE/I from non-concentrated hydrolysate which contained 12.0 g glucose/l after elution over the same column. The concentration of butyric acid in the fermented hydrolysates was 2.2 and 0.4 g/l, respectively. This reasonably low amount of butyric acid showed that the fermentation had proceeded quite well.
J Mol Microbiol Biotechnol 2000 Jan
PMID:Acetone, butanol and ethanol production from domestic organic waste by solventogenic clostridia. 1093 86

The effect of intracerebroventricular administration of mu-opioid agonist, morphine (a drug of potential abuse), and its antagonist, naloxone, followed by morphine was studied on the metabolism of acetylcholine and gamma amino butyric acid in seven discrete regions of brain from EBP-primed ovariectomized rats. We also assayed serum luteinizing hormone and follicle stimulating hormone after morphine and naloxone + morphine treatments. Cholineacetyltransferase and acetylcholinesterase, gamma-aminobutyric acid transaminase, succinic semialdehyde dehydrogenase and glutamate dehydrogenase activities were found to decrease significantly in hypothalamic as well as other brain regions studied. Naloxone given prior to morphine injection was seen to reverse the effect of morphine on enzymes activities. Our study provides evidence that opioidergic modulation of GnRH release is mediated through cholinergic and GABAergic neurotransmission besides monoaminergic control and the results may further help to elucidate the basis of neuronal dysfunction in opiate addicts.
Mol Cell Biochem 2001 Mar
PMID:Role of cholinergic and GABAergic neurotransmission in the opioids-mediated GnRH release mechanism of EBP-primed OVX rats. 1135 44

Previous studies have suggested that a gamma-amino-butyric acid (GABA) deficit in the caudal hypothalamus (CH) of the spontaneously hypertensive rat (SHR) contributes to elevated levels of arterial pressure. The purpose of this study was to examine if SHR that underwent exercise training demonstrated a blunted development of hypertension and greater levels of glutamic acid decarboxylase (GAD) mRNA transcripts in the caudal hypothalamus. SHR were randomly paired and assigned to either a trained group (T; n=9) or a non-trained control group (NT; n=9). Trained animals were exercised for 10 weeks on a motorized treadmill while NT animals concurrently rested on a mock-treadmill. Following the 10-week training period, Northern blot analyses of mRNA for both the 65-kDa (GAD(65)) and 67-kDa (GAD(67)) isoforms of GAD were performed on tissue from caudal hypothalamic and cerebellar control brain regions. Exercise training simultaneously blunted the developmental rise in blood pressure in SHR (Delta59+/-9 mmHg in trained versus Delta77+/-9 mmHg in non-trained; P<0.03) and increased both GAD(65) (147+/-44%) and GAD(67) (162+/-77%) mRNA transcript levels in the CH (P<0.05). In contrast, no difference was detected in GAD mRNA levels in the cerebellum between T and NT SHR. These findings are consistent with our previous functional studies and demonstrate that exercise can significantly and specifically upregulate GAD gene transcript levels in the caudal hypothalamus of hypertensive rats.
Brain Res Mol Brain Res 2001 Nov 01
PMID:Chronic exercise increases GAD gene expression in the caudal hypothalamus of spontaneously hypertensive rats. 1168 76

It has been shown that mesothelioma expresses the antiapoptotic protein BCL-XL, but not BCL-2, rendering bcl-xl gene expression a potential therapeutic target. Sodium butyrate (NaB) is a histone deacetylase inhibitor capable of alteration of bcl-2 family protein expression in other tumor types. Mesothelioma cell lines (REN, I-45) were exposed to NaB, and viability (colorimetric assay) and apoptosis (TUNEL, Hoescht staining, flow cytometry) were evaluated. Effects on bcl-2 family protein, fas-fas ligand, and caspases were examined by Western blot analysis and functional assay. An RNase assay evaluated bcl-2 family messenger RNA (mRNA) expression. Overexpressing BCL-XL mesothelioma clones were created by plasmid transfer. Cells were sensitive to NaB at low IC(50) (REN, 0.3 mM; I-45, 1 mM) and demonstrated apoptosis (percentage of cells below G1 phase by flow cytometry [sub-G1]: REN, 38.5%; I-45, 30.9%). A significant decrease in BCL-XL protein expression was noted with BAK, BAX, and BCL-2 unchanged, and this was corroborated at the transcriptional level with selectively decreased bcl-xl mRNA production after sodium butyrate exposure. Fas expression and fas-fas ligand sensitivity were unchanged. Caspases demonstrated low-level activation. Stable overexpressing BCL-XL clones were proportionally resistant to the NaB effect. This study suggests that mesothelioma cells are sensitive to the induction of apoptosis related to the attenuation of antiapoptotic bcl-xl gene and protein expression. Additional study of the therapeutic benefit of targeting bcl-xl gene expression in mesothelioma is warranted.
Am J Respir Cell Mol Biol 2001 Nov
PMID:Histone deacetylase inhibitor downregulation of bcl-xl gene expression leads to apoptotic cell death in mesothelioma. 1171 97


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