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)

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 cyclin-dependent kinase inhibitor p21/WAF1/CIP1 is induced in many cell types in response to a variety of extracellular signals and causes cell cycle arrest in both the G1 and G2/M phases of the cell cycle. We reported previously that calcitonin (CT) receptor (CTR)-mediated growth inhibition of HEK-293 cells stably transfected with the human CTR is accompanied by a rapid and sustained induction of p21 and cell cycle arrest in G2. In the present study we have shown that CT stimulates transcription from a p21 promoter-luciferase construct. Using deletion and mutation analysis of the p21 promoter we have demonstrated that transcriptional activation of p21 by CT is p53-independent and is mediated through specific activation of Sp1-binding sites in a region of the promoter between -82 and -69, relative to the transcription start site. CTR-mediated transcriptional activation of p21 was specific for the insert-negative isoform of the human CTR. Butyrate, which was shown previously to activate the same Sp1 site, synergised with CT to increase further p21 promoter activity. These results provide the first demonstration that CTR can induce gene transcription through the constitutively expressed transcription factor Sp1, and define a mechanism of cell growth suppression that may have implications for other members of the seven-transmembrane domain G protein-coupled receptor superfamily.
J Mol Endocrinol 2000 Oct
PMID:Identification of a novel calcitonin-response element in the promoter of the human p21WAF1/CIP1 gene. 1101 46

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

Recent studies have suggested that short chain fatty acids (SCFAs) exert a therapeutic effect on some human and experimental animal diseases. Clostridium butyricum produces high levels of SCFAs in the gut lumen. The aim of the present study was to analyze the product derived from Clostridium butyricum in a culture system, and to develop methods to eliminate the odor derived from SCFAs in the product. Clostridium butyricum was incubated in CS medium for 24 h and subsequently in CS broth for 24 h. The suspension of Clostridium butyricum in the broth was centrifugated and the supernatant was analyzed. The results showed this product contained high levels of SCFAs, especially acetic acid and n-butyric acid. Many food materials were tested in order to eliminate the odor derived from SCFAs in the product. Of the food materials tested, yogurt was shown to most effectively eliminate the odor. Using a yogurt base, we prepared a special food additive. Use of the additive completely eliminated the odor of the product derived from Clostridium butyricum. Finally, we administered the product with the additive to Sprague-Dawley rats for 14 days. The rats grew normally for the duration of the experimental period. It is possible that this novel product with the additive exerts therapeutic effects on some gastointestinal disorders.
Int J Mol Med 2002 Jan
PMID:Oral administration of a product derived from Clostridium butyricum in rats. 1174 96

There is increasing evidence that intestinal microflora play an important role in the pathogenesis of ulcerative colitis. Therefore, modification of the microflora by prebiotics, probiotics, and antibiotics may be a rational approach for controlling intestinal inflammation. Germinated barley food-stuff (GBF) is an insoluble mixture of glutamine-rich protein and hemicellulose-rich dietary fiber. GBF is utilized efficiently by Bifidobacterium, Lactobacillus, and Eubacterium and converted by them into lactate, acetate, and butyrate. These bacterial organic acids preserve a favorable intestinal condition. We have previously shown that GBF has attenuated intestinal inflammation in patients with ulcerative colitis and experimental colitis models through prebiotic actions. The aim of this study was to compare the effect of GBF with that of probiotics and antibiotics in an experimental colitis model. Colitis was induced by feeding male SD rats with a diet containing 3.0-3.5% dextran sodium sulfate (DSS). The therapeutic effect of oral administration of a prebiotic (GBF), probiotics (mixture of Lactobacillus and Clostridium butyricum), antibiotics (vancomycin, metronidazole), and the vehicle was determined by assessing clinical and pathological scores on day 6 after initiation of colitis. Butyrate concentrations in the cecal content were also determined. GBF treatment significantly reduced colonic inflammation as assessed by clinical scores with an increase in cecal butyrate levels. Probiotic treatment with a mixture of Lactobacillus and Clostridium butyricum did not show such an effect. Both antibiotic treatments significantly attenuated clinical and pathological scores. However, in contrast to GBF, this treatment led to a significant decrease in cecal butyrate levels. These data suggest that modification of the intestinal microflora by prebiotics, including GBF, may serve as a useful adjunct in the treatment of ulcerative colitis as well as antibiotic treatment.
Int J Mol Med 2002 Jan
PMID:Prebiotic treatment of experimental colitis with germinated barley foodstuff: a comparison with probiotic or antibiotic treatment. 1174 99

The available data from preclinical and pharmacological studies on the role of gamma amino butyric acid (GABA) support the hypothesis that a dysfunction in brain GABAergic system activity contributes to the vulnerability to bipolar affective disorders (BPAD). Moreover, the localization of the alpha3 subunit GABA receptor GABRA3 gene on the Xq28, a region of interest in certain forms of bipolar illness, suggests that GABRA3 may be a candidate gene in BPAD. In the present study, we tested the genetic contribution of the GABRA3 dinucleotide polymorphism in a European multicentric case-control sample, matched for sex and ethnogeographical origin. Allele and genotype (in females) frequencies were compared in 185 BPAD patients and 370 controls. A significant increase of genotype 1-1 was observed in BPAD females compared to controls (P=0.0004). Furthermore, when considering recessivity of allele 1 (females with genotype 1-1 and males carrying allele 1), results were even more significant (P= 0.00002). Our findings suggest that the GABRA3 polymorphism may confer susceptibility to or may be in linkage disequilibrium with another gene involved in the genetic etiology of BPAD.
Mol Psychiatry 2002
PMID:Excess of allele1 for alpha3 subunit GABA receptor gene (GABRA3) in bipolar patients: a multicentric association study. 1184 Mar 13

The role and regulation of signal transduction pathways in proliferation and differentiation of intestinal epithelial cells are still poorly understood. However, growing evidences have been recently accumulated demonstrating that mitogen-activated protein kinases (MAPKs) play a pivotal function in the normal development of intestine. We have investigated, in the intestinal cell line HT-29, the regulation (namely activity and phosphorylation degree) of MAP kinases ERK 1 (p44) and ERK 2 (p42) during differentiation. Addition of fetal calf serum to HT-29 undifferentiated resting cells caused a rapid phosphorylation of both ERKs and an increase of their specific kinase activity. Moreover, nuclear translocation of ERK 1 and ERK 2 occurred concurrently to their activation, leading to the conclusion that ERK 1 and ERK 2 are classically regulated when quiescent HT-29 cells are induced to proliferate. Butyrate addition to the intestinal cell line resulted in terminal differentiation and in a selective down-regulation of ERK 2 activity (and phosphorylation degree) without any effect on ERK 1. Conversely, when HT-29 cells were differentiated by repeated passages in a glucose-free medium, we observed a progressive dephosphorylation and inactivation of p42 and p44 kinases along with the failure of serum to activate both the enzymes. Our findings suggest that, during the differentiation of intestinal cells, remarkable changes occur in ERK 1 and ERK 2 control mechanisms leading to an unresponsiveness of MAP kinase pathway.
Mol Cell Biochem 2002 Feb
PMID:Down-regulation of ERK1 and ERK2 activity during differentiation of the intestinal cell line HT-29. 1195 64

FMRFamide-like immunoreactivity (FLI) was localized in the eyestalk of Penaeus monodon by immunohistochemistry using a combination of three anti-FMRFamide-like peptide (FLPs) monoclonal antibodies. Approximately 3000 small neuronal cell bodies in the lamina ganglionalis; 100 medium to large size at the ganglion between the medulla interna and the medulla terminalis; and 250 medium size around the medulla terminalis were stained intensely. The neuronal processes in neuropils of the medulla externa, medulla interna, medulla terminalis, sinus gland and some nerve fibers in the optic nerve were also recognized. The small cell bodies, approximately 1500 cells, anterior to the medulla externa were stained inconsistently and the neuronal processes were not observed from these cells. Isolation of FLPs from 9000 eyestalks was performed using methanol/acetic/water (90:1:9) extraction. After the extract was partially purified using C18 cartridges, it was further purified by five to seven steps of RP-HPLC using three kinds of columns: C18; C8; and cyano, and three solvent systems: acetonitrile/trifluoro acetic acid; aceonitrile/heptafluoro butyric acid; and acetonitrile/triethyl ammonium acetate. Dot-ELISA using the combination of the same antibodies was used to monitor FLPs in the fractions during purification processes. Seven new sequences of FLPs were identified which can be divided into four subgroups according to the primary structure of the C-terminus: (1) GDRNFLRFamide; (2) AYSNLNYLRFamide; (3) AQPSMRLRFamide, SQPSMRLRFamide, SMPSLRLRFamide and DGRTPALRLRFamide; and (4) GYRKPPFNGSIFamide. These data indicate the high complexity of this peptide family in which multiple forms are usually exist.
Comp Biochem Physiol B Biochem Mol Biol 2002 Mar
PMID:Seven novel FMRFamide-like neuropeptide sequences from the eyestalk of the giant tiger prawn Penaeus monodon. 1195 15


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