Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neural cell adhesion molecule (N-CAM), is expressed in definite spatiotemporal patterns during development. To identify factors that may influence place-dependent n-cam gene expression, we have studied the binding and activation of the n-cam promoter by Pax-8, a member of the Pax family of transcription factors. Pax-8 increased n-cam promoter activity 13.4-fold in cellular co-transfection experiments, and a short segment of the promoter (-143 to -15) mediated the response. This region of the n-cam promoter produced a DNA-protein complex when incubated with either extracts from COS-7 cells transfected with the Pax-8 expression vector or a Pax-8/GST fusion protein. Pax-8 bound to the n-cam promoter through two TGCTCC motifs (designated PBS-1 and PBS-2) that resemble paired domain binding sites. Mutation of PBS-1 and PBS-2 eliminated Pax-8 activation of the n-cam promoter. Transfection of N2A neuroblastoma cells with the Pax-8 expression vector resulted in a 5-fold increase in the transcription of the endogenous n-cam gene. The combined results suggest that Pax-8 activates transcription of the n-cam gene through binding of sequences resembling paired domain binding sites in the n-cam promoter. The data raise the possibility that the n-cam promoter may be regulated by other members of the Pax gene family.
 ...
PMID:Binding and activation of the promoter for the neural cell adhesion molecule by Pax-8. 807 51

Leptin is a hormone that is secreted by adipocytes and regulates body weight through its effect on satiety and energy metabolism. The ob/ob mouse is deficient in this protein and is characterized by obesity and other metabolic disorders. This study investigated the alterations of several hepatic cytochrome P-450 (CYP), conjugation, and antioxidant enzymes in lean and ob/ob mice and the role leptin plays in the modulation of these enzymes. Lean and ob/ob male mice were injected with leptin (100 microg) or PBS for 15 days. Liver microsomes from ob/ob mice, when compared with lean controls, displayed significantly reduced chlorzoxazone 6-hydroxylation activity (27%); however, 7alpha- and 16alpha- testosterone hydroxylation and pentoxyresorufin O-dealkylation activities were significantly higher (47%, 22%, and 39%, respectively). Leptin administration corrected alterations seen with all P-450 activities. Dealkylation of ethoxyresorufin and omega-hydroxylation of lauric acid activities from ob/ob and lean mice were not statistically different; however, leptin exposure significantly increased ethoxyresorufin activity in lean mice (14%) and decreased the activity in ob/ob mice (36%). UDP-glucuronosyl-transferase and glutathione S-transferase activities were not altered. The antioxidant enzymes, catalase (11%) and glutathione peroxidase (26%), as well as glutathione reductase (17%), were lower in the ob/ob mice and leptin treatment corrected these alterations. The results of this study demonstrate alterations in constitutive expression of CYP2B, CYP2E, CYP2A, catalase, glutathione peroxidase, and glutathione reductase in ob/ob mice that were restored to lean control values following leptin treatment. Additionally, CYP3A activity was increased following leptin treatment in ob/ob mice. The mechanism for the observed alterations may be due to direct leptin effects or via indirect alterations in insulin, corticosterone, and/or growth hormone.
 ...
PMID:Effect of leptin on cytochrome P-450, conjugation, and antioxidant enzymes in the ob/ob mouse. 1034 99

The potential of a recombinant Schistosoma bovis 28-kDa glutathione S-transferase (rSb28GST) to protect cattle against Fasciola hepatica was tested in a vaccination trial. Thirty two calves were randomly divided into four groups of eight animals. Calves of the three vaccine groups received two intramuscular injections at 3 weeks interval, of 0.250mg rSb28GST in either aluminium hydroxide (Al(OH)(3)), Quil A, or PBS emulsified in an equal volume of Freund's complete adjuvant (FCA).Animals of the control group received injections of Al(OH)(3)/PBS only. All animals were challenged orally with a total of 360 metacercariae of F. hepatica, spread over 6 weeks. All groups of vaccinated animals produced measurable IgG antibody titers to rSb28GST after vaccination. Animals immunised with FCA adjuvanted vaccine had the highest and more durable antibody titers and only sera from this group recognised an approximately 24kDa protein band from F. hepatica, that is thought to be a F. hepatica GST. Despite a good antibody response differences in cumulative faecal egg output between the groups were not statistically significant. In addition, no significant difference was found between groups in terms of total worm numbers or percentage of immature flukes recovered at necropsy. In conclusion, the recombinant S. bovis 28kDa GST was not found to adequately protect cattle against experimental F. hepatica challenge, using either aluminium hydroxide, Quil A or FCA as adjuvant.
 ...
PMID:Failure of a recombinant Schistosoma bovis-derived glutathione S-transferase to protect cattle against experimental Fasciola hepatica infection. 1269 38

A family of specific carrier protein designated as monocarboxylate transporter (MCT) has been known to transport the lactate and other moncarboxylates in mammalian cells. We hypothesized the presence of serum protein in human circulation that may works as a lactate carrier and that biochemical structure would possesses common structure with MCT on the plasma membrane. Immunoblot analysis with an anti-MCT1 polyclonal antibody suggested the presence of a 44-kDa protein in human circulation and N-terminal amino acid sequencing exhibited a stretch of 14 amino acids which is completely identical to MCT1. The unbound fractions from the GST-MCTI fusion protein-immobilized glutathione sepharose 4B column demonstrated that lactic acid concentration began to increase with one fraction delay compared to Sepharose 4B and GST-immobilized column. When lactic acid was washed away with PBS, lactic acid concentrations in the effuluent constantly decreased in both Sepharose 4B and GST-immobilized column. However, GST-MCT1-immobilized column showed specific convex curve from fraction approximately 3 mM of lactate and demonstrated wash out delay compared to Sepharose 4B and GST-immobilized column. These observations demonstrated biochemical and immunological similarities between a 44-kDa protein purified from human serum and MCT1 present on the plasma membrane. The studies on MCT1-fusion protein suggested possible functional properties of a 44-kDa protein as a lactate buffer by holding and unhand a lactate according to the lactate concentration in human blood. The experiments described herein have suggested the existence of lactate carrier in human circulation which is free from plasma membrane.
 ...
PMID:A 44-kDa of protein identical to the N-terminal amino acid sequence of MCT1 in human circulation. 1287 Jun 77

Proteins capable of selective and specific inhibition of cysteine protease have been identified as cystatins and are isolated from a variety of microbes and tissues of animals and plants. The physiological function of these proteins has been proposed to be the regulation of protein turnover and defense against pathogens as well as the balance of the host-parasite immune relationship. Genes encoding cystatins have been found in several species of ticks, but the function of cystatin in ticks is not understood. We cloned a gene encoding cystatin from tick H. longicornis and designated it as Hlcyst-2 (H. longicornis cystatin-2). Its full-length cDNA is 569 bp, and it encodes a putative 133 amino acid protein with an obvious signal peptide. Sequence analysis demonstrated that it has significant homology with the known cystatin. The recombinant protein was expressed in a GST-fused soluble form in Escherichia coli and purified by affinity chromatography. The inhibitory activity of the recombinant protein against papain, cathepsin L, and cathepsin B was identified by fluorogenic substrate analysis. Cystatin was mostly expressed in the tick midgut and hemocyte. Blood feeding induced significantly increased expression in the midgut. Real-time PCR confirmed that LPS-injected adult ticks expressed Hlcyst-2 1.6 more times than the PBS-injected control; Babesia gibsoni-infected larvae ticks expressed Hlcyst-2 1.8 more times than normal larvae ticks. The recombinant protein also showed a significant growth-inhibitory effect on Babesia bovis cultured in vitro. These results indicated this cystatin Hlcyst-2 is involved in tick innate immunity.
 ...
PMID:A secreted cystatin from the tick Haemaphysalis longicornis and its distinct expression patterns in relation to innate immunity. 1683 18

Temporal changes in physiological spaces, protein expression of transporters and enzymes, and enalapril removal were appraised in the metastatic liver tumor model developed from male Wag/Rij rats after the intraportal injection of CC531 colon adenocarcinoma cells; sham-operated preparations received PBS. Liver tissue spaces, investigated with multiple indicator dilution technique in liver perfusion studies, were unchanged at week 3 after tumor induction. At week 4, however, the sinusoidal blood volume and albumin Disse space in tumor-bearing livers were slightly lower compared with those of shams. Increased levels of the canalicular ATP transporters, P-glycoprotein, multidrug resistance-associated protein 2 (Mrp2), and bile salt export pump (Bsep) at week 2 (P < 0.05), unchanged levels of Ntcp, Oatp1a1, Oatp1a4, and Mct2, but decreased levels of cytochrome P450 3a2 (Cyp3a2) and glutathione S-transferase (Gst4-4) at week 4 (P < 0.05) were observed in peritumor vs. sham-operated liver tissues with Western blotting. The steady-state extraction ratio of enalapril, a substrate that enters the liver rapidly via Oatp1a1 and primarily undergoes metabolism by the carboxylesterases, was unaffected by liver metastasis at week 4 regardless of its delivery via the portal vein or hepatic artery into the perfused liver preparations.
 ...
PMID:Transporters, enzymes, and enalapril removal in a rat (CC531-induced) liver metastatic model. 1785 65

Almost all human malignant tumours exhibit strong telomerase activity, but normal adult tissues, with a few exceptions, do not. hTERT (human telomerase reverse transcriptase) is an essential component of telomerase, and hence it can serve as a parallel sign in the diagnosis and prognosis of cancers. In the present study, we selected a sequence of hTERT containing two antigenic epitopes that have high affinity for HLA-A2 (human leucocyte antigen-A2) as a TAA (tumour-associated antigen) based on a peptide-motif scoring system. The sequence was obtained by reverse-transcriptase PCR and cloned into the Escherichia coli expression vector pGEX-4T-1. The expression product appeared in the form of inclusion bodies. Denatured inclusion-body extract was subjected to SDS/PAGE, and the gel band corresponding to the putative 38 kDa fusion protein (GST-hTERT major tumour-associated antigen) was excised, ground with PBS, mixed with Freund's adjuvant and used to inoculate mice, generating anti-TERT polyclonal antibodies. Western blotting using the leukaemia cell line THP-1 demonstrated that the antibodies were able to detect hTERT expression, implying the potential applicability of the antigenic peptides derived from hTERT as a universal marker in the diagnosis and prognosis of tumours.
 ...
PMID:Characterization of a human telomerase reverse transcriptase sequence containing two antigenic epitopes with high affinity for human leucocyte antigen. 1786 23

Amnesic shellfish poisoning toxin domoic acid (DA) is a marine neurotoxin that accumulates in fish and shellfish, and has been implicated to be involved in human and marine wildlife mortality. The transcriptional responses of cytochrome P-450 1A (CYP1A), glutathione S-transferase alpha (GSTA), glutathione S-transferase rho (GSTR), heat shock protein 70 (HSP70), and Na(+)/K(+)-ATPase alpha 1 (ATP1A1) in the liver of rabbitfish (Siganus oramin) intracoelomically injected with DA, were investigated. Experimental fish were administered with one injection of DA (2 microg/g wet weight) or PBS as control. After 24 h, fish were killed and hepatic RNA was isolated. Partial cDNA of rabbitfish CYP1A, GSTA, GSTR, HSP70, ATP1A1, and beta-actin were obtained by PCR using degenerate primers. Using beta-actin as an external control, the relative liver CYP1A, GSTA, GSTR, HSP70, and ATP1A1 mRNA abundance of rabbitfish were determined by semi-quantitative RT-PCR within the exponential phase. The ratio CYP1A/beta-actin mRNA (%) of exposure group was determined to be 148.92+/-12.69, whereas the ratio of control group was 82.3+/-8.35, indicating that CYP1A was induced significantly in rabbitfish following DA exposure (P<0.05). Although the expressions of GSTA, HSP70, and ATP1A1 tended to increase and GSTR tended to decrease, no significant changes were found (P>0.05). The induction of hepatic CYP1A in response to DA suggests a potential role for fish phase I xenobiotic metabolizing enzyme in DA metabolism.
 ...
PMID:Transcriptional responses of xenobiotic metabolizing enzymes, HSP70 and Na+/K+ -ATPase in the liver of rabbitfish (Siganus oramin) intracoelomically injected with amnesic shellfish poisoning toxin. 1821 93

Oxidative stress is an important factor in the pathogenesis of asthma. Furthermore, antioxidants like GST are reduced in asthma patients. In the present study, the therapeutic effects of exogenous GST and mGST were evaluated in a mice model. GST mutated at residues 21/27 has reduced IgE binding with similar enzyme activity as that of GST. To evaluate the therapeutic effects of GST, BALB/c mice were immunized and challenged with ovalbumin. Mice were given GST, mGST, and alpha-lipoic acid by inhalation and sacrificed on Day 31 to evaluate inflammation and oxidative stress. Mice treated with mGST showed significantly reduced total cell count (P<0.01) and eosinophils (P<0.01) in BALF compared to GST- or PBS-treated groups. The lung inflammation score was lowest for the mGST-treated group along with reduced IL-4 (P<0.01) and OVA-specific IgE than other groups. Oxidative stress as per the lipid peroxidation level in BALF of mGST-treated mice was reduced significantly in comparison to PBS- or GST-treated mice. In conclusion, inhalation of mGST reduced airway inflammation in mice. Mutated GST with reduced allergenicity has better therapeutic potential and can be explored as an adjunct therapy in asthma.
 ...
PMID:Mutated glutathione-S-transferase reduced airway inflammation by limiting oxidative stress and Th2 response. 1878 35

Leptospira is an important infectious Gram-negative bacterium causing Leptospirosis in mammals. Outer membrane proteins (OMPs) are key molecules in the interface between the cell and its environment. A group of putative leptospiral outer membrane proteins with an OmpA-like domain, comprising Lp0056, Lp0222, Lp3615, Lp3685, Lp4337 and Lbp328, were identified by bioinformatic methods and expressed as GST-tag fusion proteins. All these recombinant proteins were screened for immune-protective potential in hamsters challenged with Leptospira interrogans serovar Pomona. Out of these six proteins, three fusion proteins including Lp4337, Lp3685 and Lp0222 were found to be protective on the basis of survival. The immune response generated against these three recombinant proteins was evaluated on the basis of antibody production, lymphocyte proliferation and cytokine profiles in response to recall antigens whereas protective efficacy was assessed on the basis of survival and histopathological lesions in the vital organs (kidney, liver, and lung). Our results show that all three recombinant proteins generated strong immune responses, enhanced survival and reduced the severity of histopathological lesions. Of the proteins studied, Lp4337 generated the strongest immune response and was able to impart maximum protection (75%), followed by Lp3685 (58%), whereas Lp0222 generated lowest immune response correlating to protection (42%) against lethal infection of leptospira in the immunized animals. In contrast, control animals injected with PBS demonstrated low survival and had significant lesions. All these results clearly indicate that these three OmpA-like proteins may serve as novel vaccine candidates for leptospirosis.
 ...
PMID:Identification and characterization of OmpA-like proteins as novel vaccine candidates for Leptospirosis. 2006 77


1 2 3 Next >>