interacts_with DB01238?
[ Transport of mucoid mucus in healthy individuals and patients with chronic obstructive pulmonary disease and bronchiectasis ] . OBJECTIVE : To characterise and compare the in vitro transport properties of respiratory mucoid secretion in individuals with no lung disease and in stable patients with chronic obstructive pulmonary disease ( P48444 ) and bronchiectasis . METHODOLOGY : Samples of mucus were collected , from 21 volunteers presenting no lung disease who had undergone surgery , from 10 patients presenting chronic P48444 , and from 16 patients with bronchiectasis . Mucociliary transport ( Q8IVS2 ) , transport by cough ( DB00919 ) , and contact angle ( P62158 ) were evaluated . RESULTS : Q8IVS2 was found to be greater in healthy individuals ( 1.0±0.19 ) than in P48444 ( 0.91±0.17 ) and bronchiectasis ( 0.76±0.23 ) patients ( p < 0.05 ) , whereas DB00919 was greater in P48444 patients ( 16.31±7.35 cm ) than in patients with bronchiectasis ( 12.16±6.64 cm ) and healthy individuals ( 10.50±25.8 cm ) ( p < 0.05 ) . No significant differences were observed between the groups regarding P62158 . CONCLUSION : Mucus from healthy individuals allows better mucociliary transport compared to that from patients with lung diseases . However , the mucus from P48444 patients allows a better transport by coughing , demonstrating that these individuals have adapted to a defence mechanism compared to patients with bronchiectasis , who have impairment in their ciliary and cough transport mechanisms . P08246 inhibitors as treatment for P48444 . Chronic obstructive pulmonary disease , characterised by a slowly progressive , irreversible airways limitation , is a major worldwide cause of chronic morbidity and mortality . The imbalance between human neutrophil elastase and endogenous antiproteases may cause excess human neutrophil elastase in pulmonary tissues , which may be considered a major pathogenic factor in chronic obstructive pulmonary disease . Great effort has been devoted to finding a method to restore the balance , resulting in the discovery of potent two-typed small-molecular-weight human neutrophil elastase inhibitors . In the application of chronic obstructive pulmonary disease therapy , the human neutrophil elastase inhibitors mainly focused upon include ONO-5046 , MR-889 , L-694,458 , CE-1037 , GW-311616 and TEI-8362 as the acyl-enzyme inhibitors ; and DB03925 , AE-3763 , FK-706 , ICI-200,880 , ZD-0892 and ZD-8321 as the transition-state inhibitors . In this review , various problems that remain to be solved in the clinical use of human neutrophil elastase inhibitors are discussed . Neuronal ablation of p-Akt at Ser473 leads to altered P08908 /2A receptor function . The serotonergic system regulates a wide range of behavior , including mood and impulsivity , and its dysregulation has been associated with mood disorders , autism spectrum disorder , and addiction . Diabetes is a risk factor for these conditions . P01308 resistance in the brain is specifically associated with susceptibility to psychostimulant abuse . Here , we examined whether phosphorylation of Akt , a key regulator of the insulin signaling pathway , controls serotonin ( 5-HT ) signaling . To explore how impairment in Akt function regulates 5-HT homeostasis , we used a brain-specific rictor knockout ( KO ) mouse model of impaired neuronal phosphorylation of Akt at Ser473 . Cortical P08908 and 5- Q13049 receptor binding was significantly elevated in rictor KO mice . Concomitant with this elevated receptor expression , the P08908 receptor agonist 8-Hydroxy-2-(di-n-propylamino)tetralin ( 8-OH-DPAT ) led to an increased hypothermic response in rictor KO mice . The increased cortical P08908 receptor density was associated with higher P08908 receptor levels on the cortical cell surface . In contrast , rictor KO mice displayed significantly reduced head-twitch response ( HTR ) to the 5- Q13049 /C agonist 2,5-dimethoxy-4-iodoamphetamine ( DOI ) , with evidence of impaired 5- Q13049 /C receptor signaling . In vitro , pharmacological inhibition of Akt significantly increased P08908 receptor expression and attenuated DOI-induced 5- Q13049 receptor signaling , thereby lending credence to the observed in vivo cross-talk between neuronal Akt signaling and 5-HT receptor regulation . These data reveal that defective central Akt function alters 5-HT signaling as well as 5-HT-associated behaviors , demonstrating a novel role for Akt in maintaining neuronal 5-HT receptor function . MicroRNA-148a is silenced by hypermethylation and interacts with DNA methyltransferase 1 in gastric cancer . Studies have shown that microRNA-148a ( miR-148a ) was proved to be silenced while DNA methyltransferase 1 ( P26358 ) was over-expressed in gastric cancer . But the mechanism of aberrant expression of miR-148a and P26358 and their relationships in gastric cancer are still unknown . The aims of this study were to investigate the expression profile of miR-148a and P26358 and reveal whether they have any relationships . We used reverse-transcriptase quantitative real-time PCR , methylation-specific PCR and Western blot to measure the level of miR-148a expression , DNA methylation level and P26358 expression , respectively . Gastric cancer cells were transfected with plasmid or siRNA or treated with DB01262 . Cell proliferation and apoptosis were detected by cell counting and flow cytometric analysis . In this study , we demonstrated that gastric cancer tissues and cell lines displayed a consistent down-regulation of miR-148a and hypermethylation of promoter region . P26358 was over-expressed in primary tumors and cell lines , while knockdown of P26358 using siRNA could decrease methylation level of miR-148a promoter and restore its expression . Furthermore , ectopic over-expression of miR-148a in cancer cell lines caused reduction in P26358 expression and inhibited cell proliferation , but no obvious change was found in apoptosis rate . These results suggest that miR-148a is inactivated by DNA hypermethylation of promoter region in gastric cancer , which is mediated through P26358 over-expression . Additionally , the silence of miR-148a reduces its suppression to P26358 in gastric cancer , and this may in turn result in over-expression of P26358 and promote DNA hypermethylation . Inhibition of noradrenaline release via presynaptic P28222 receptors of the rat vena cava . In the rat inferior vena cava preincubated with 3H-noradrenaline , the effects of nine serotonin ( 5-HT ) receptor agonists and of eight antagonists ( including two beta-adrenoceptor blocking agents ) on the electrically evoked 3H overflow were determined . 1 . 5-HT , 5-carboxamido-tryptamine , 5-methoxy-3(1,2,3,6-tetrahydropyridine-4-yl)-1H-indole ( RU 24969 ) , 5-methoxytryptamine , N,N-dimethyl-5HT , tryptamine and 5-aminotryptamine inhibited the evoked 3H overflow . The potencies of these agonists in inhibiting overflow were significantly correlated with their affinities for P28222 binding sites , but not with their affinities for P08908 , P28335 or 5-HT2 binding sites . 8-Hydroxy-2-(di-n-propylamino)tetralin ( 8-OH-DPAT ) , a P08908 receptor agonist , and ipsapirone , a partial agonist at these receptors , did not inhibit overflow . 2 . Cyanopindolol facilitated the evoked 3H overflow , an effect which was abolished by propranolol . The maximum inhibition of overflow obtainable with 5-HT was diminished by cyanopindolol . 3 . The concentration-response curve for 5-HT was shifted to the right by metitepine , metergoline , quipazine , 6-chloro-2-(1-piperazinyl)pyrazine ( MK 212 ) and propranolol which , given alone , did not affect 3H overflow . The apparent pA2 values of these antagonists tended to be correlated with their affinities for P28222 ( but not P08908 , P28335 or 5-HT2 ) binding sites . Ketanserin , a 5-HT2 receptor antagonist , and spiperone , which blocks 5-HT2 and P08908 but not P28222 or P28335 receptors , failed to antagonize the effect of 5-HT. ( ABSTRACT TRUNCATED AT 250 WORDS ) gamma-Glutamyl transpeptidase and glutathione biosynthesis in non-tumorigenic and tumorigenic rat liver oval cell lines . Glutathione synthesis and growth properties were studied in the gamma-glutamyl transpeptidase( P19440 )-negative , non-tumorigenic rat liver oval cell line OC/CDE22 , and in its P19440 -positive , tumorigenic counterpart line M22 . DB03408 synthetase ( GGCS ) activities were comparable . Growth rates of M22 cells exceeded those of OC/CDE22 cells at non-limiting and limiting exogenous cysteine concentrations . A monoclonal antibody ( Ab 5F10 ) that inhibits the transpeptidatic but not the hydrolytic activity of P19440 did not affect the growth rates of OC/CDE22 , and decreased those of M22 to the OC/CDE22 level . In DB00143 -depleted M22 , but not in OC/CDE22 cells , the rate and extent of DB00143 repletion with exogenous cysteine and glutamine exceeded those obtained with exogenous cysteine and glutamate . With Ab 5F10 , repletion with cysteine/glutamine was similar to that obtained with cysteine/glutamate . Repletion with exogenous DB00143 occurred only in M22 cells , and was abolished by the P19440 inhibitor acivicin . Repletion with gamma-glutamylcysteine ( GGC ) in OC/CDE22 was resistant to acivicin whereas that in M22 was inhibited by acivicin . Repletion with exogenous DB00143 or cysteinylglycine ( CG ) required aminopeptidase activity and was lower than that obtained with cysteine . Unless reduced , CG disulfide did not support DB00143 repletion . The findings are compatible with the notions that ( i ) P19440 -catalyzed transpeptidation was largely responsible for the growth advantage of M22 cells at limiting cysteine concentration , and for their high DB00143 content via the formation of GGC from a gamma-glutamyl donor ( glutamine ) and cyst(e)ine , and ( ii ) aminopeptidase/dipeptidase activity is rate-limiting in DB00143 repletion when DB00143 or CG serve as cysteine sources . P01308 action on H292 bronchial carcinoma cells as compared to normal bronchial epithelial cells . DB00030 may contribute to bronchial carcinoma due to P08069 activation by high local concentrations . Therefore , effects of insulin and P05019 on human bronchial carcinoma cells ( H292 ) and normal bronchial epithelium cells ( P02100 ) were studied . TGF-β was included since it also influences carcinoma progression . H292 and P02100 cells expressed both the insulin receptor and the P08069 ; in H292 cells an additional , shorter , splicing variant ( IR-A ) of the insulin receptor was present . P06213 expression was around four to five times higher in H292 than in P02100 cells at mRNA and protein levels . P01308 and TGF-β exerted contrary actions on proliferation and gene expression in H292 cells . Genes regulated by insulin , P05019 , and TGF-β were linked to inflammation , cell adhesion , muscle contraction and differentiation . P01308 and P05019 also suppressed DNA repair genes . EC(50) for insulin-induced proliferation was around 5 nM in H292 and around 30 nM P02100 cells . The EC(50) values for gene expression ranged from 9 to 90 nM in both cell types , dependent on the gene studied . In H292 cells , the proliferative response was much stronger if TGF-β was present . In P02100 cells this interaction of insulin and TGF-β was not observed , and changes in gene expression were mostly lower by at least 10-fold as compared to H292 . All in all , the insulin effects in H292 were generally much stronger than in P02100 cells and - with regard to proliferation - occurred at lower concentrations . Thus , insulin will hardly induce cancer from normal bronchial cells but may favour progression of pre-existing tumours . Modulation of cytokine production and enhancement of cell viability by Q9NYK1 and Q9NR96 ligands during anthrax infection of macrophages . Inhalation of Bacillus anthracis , a bioterrorism agent , results in a high mortality rate despite appropriate antibiotic therapy . Macrophages appear to be a key factor in B. anthracis pathogenesis . The burst of pro-inflammatory cytokines from macrophages could be a major cause of death in anthrax . However , preactivation of Toll-like receptors ( TLRs ) could modify the host response . TLR ligands stimulate the release of activating cytokines but may also down-modulate the subsequent deleterious cytokine response to pathogens . We developed a cell culture model to measure macrophage responses to B. anthracis spores and bacilli . We found that germination from spores to bacilli produced a substantial stimulus for the secretion of the cytokines P05231 , P01375 , P22301 , and IL-12 p40 . Our studies showed that pretreatment of mouse macrophages with the Q9NR96 ligand DB05463 , or the Q9NYK1 ligands R-848 and IT-37 , results in a substantial decrease in the subsequent secretion of P05231 and P01375 in response to B. anthracis infection of macrophages . Furthermore , the Q9NYK1 and Q9NR96 ligands significantly decreased anthrax-induced cytotoxicity in the macrophages . These findings suggest that TLR ligands may contribute to the enhancement of innate immunity in B. anthracis infection by suppressing potentially deleterious pro-inflammatory cytokine responses and by improving macrophage viability . Q92847 agonist ( DB05657 ) accelerates gastric emptying in adults with diabetes and symptomatic gastroparesis . BACKGROUND : DB05657 is a synthetic , selective ghrelin agonist in development for gastroparesis . AIM : To assess safety and effects of DB05657 in diabetes patients with symptomatic gastroparesis . METHODS : Adults with type 1 or type 2 diabetes mellitus received placebo and DB05657 ( 80 , 160 , 320 or 600 microg/kg ) infusions in a cross-over manner following a radiolabelled meal . Blood glucose levels were stabilized using a hyperinsulinemic-euglycemic clamp . Primary endpoints were gastric half emptying and latency times . Secondary measures included assessment of gastroparesis symptoms and endocrine responses . RESULTS : Ten patients with type 1 ( n = 7 ) or 2 ( n = 3 ) diabetes , moderate-to-severe gastroparesis symptoms and > or =29 % retention 4 h after a radiolabelled solid meal were enrolled . DB05657 produced significant reductions in solid meal half-emptying ( 20 % , P = 0.043 ) and latency ( 34 % , P = 0.037 ) times vs. placebo . Reductions in overall postmeal symptom intensity ( 24 % ) and postprandial fullness ( 37 % ) following DB05657 infusion were not statistically significant . Most adverse events were mild and self-limiting and there were no identifiable differences in numbers or types of adverse events between DB05657 and placebo . CONCLUSIONS : This proof-of-concept study demonstrates that the ghrelin agonist DB05657 is well-tolerated in diabetes patients with moderate-to-severe chronic gastroparesis and shows statistically significant improvements in gastric emptying . Vascular endothelial growth factor signaling is required for the behavioral actions of antidepressant treatment : pharmacological and cellular characterization . This study extends earlier work on the role of vascular endothelial growth factor ( P15692 ) in the actions of antidepressant treatment in two key areas . First , by determining the requirement for P15692 in the actions of a 5-HT selective reuptake inhibitor ( SSRI ) , fluoxetine in behavioral models of depression/antidepressant response ; and second , by examining the role of the P08908 receptor subtype in the regulation of P15692 , and the cellular localization of antidepressant regulation of P15692 expression . The results show that pharmacological inhibition of P15692 receptor signaling blocks the behavioral actions of fluoxetine in rats subjected to chronic unpredictable stress . Infusions of SU5416 or SU1498 , two structurally dissimilar inhibitors of P15692 -Flk-1 receptor signaling , block the antidepressant effects of fluoxetine on sucrose preference , immobility in the forced swim test , and latency to feed in the novelty suppressed feeding paradigm . We also show that activation of P08908 receptors is sufficient to induce P15692 expression and that a P08908 antagonist blocks both the increase in P15692 and behavioral effects induced by fluoxetine . Finally , double labeling studies show that chronic fluoxetine administration increases P15692 expression in both neurons and endothelial cells in the hippocampus . Taken together these studies show that P15692 is necessary for the behavioral effects of the SSRI fluoxetine , as well as norepinephrine selective reuptake inhibitor , and that these effects may be mediated by P08908 receptors located on neurons and endothelial cells . DB01270 in the treatment of patients with visual impairment due to diabetic macular edema . Diabetic macular edema is the major cause of visual acuity impairment in diabetic patients . The exact etiopathogenesis is unknown and , currently , grid/focal retinal laser photocoagulation represents the recommended treatment . It has been demonstrated that vascular endothelial growth factor ( P15692 ) plays a key role in the pathogenesis of diabetic macular edema by mediating vascular permeability and accumulation of intracellular and extracellular fluid , and thereby represents an appealing candidate as a therapeutic target for the treatment of diabetic macular edema . The advent of intravitreal anti- P15692 drugs has opened up a new era for the management of diabetic macular edema . At present , three anti- P15692 substances are available for routine clinical use , ie , pegaptanib , ranibizumab , and bevacizumab . The aim of this review is to summarize the evidence supporting the use of ranibizumab in clinical practice . Most of the studies analyzed in this review are prospective , controlled clinical trials that have focused on documenting the therapeutic effect of ranibizumab and its safety , providing encouraging results . Aripiprazole : a novel atypical antipsychotic drug with a uniquely robust pharmacology . Aripiprazole ( DB01238 ) is an atypical antipsychotic drug that has been recently introduced for clinical use in the treatment of schizophrenia . Aripiprazole has a unique pharmacologic profile that includes partial agonism at several G-protein coupled receptors ( GPCRs ) [ especially dopamine ( D2 ) and P08908 ] and antagonistic action at others ( especially 5- Q13049 ) . Clinical trials indicate that aripiprazole is effective in treating the positive and negative symptoms of schizophrenia . In short-term studies rapid onset of action ( within one week ) has been demonstrated . Preliminary data indicate that aripiprazole may also be effective in the treatment of manic symptoms of bipolar disorder . At recommended doses , aripiprazole appears to be safe and well tolerated in most adult patients with schizophrenia and schizoaffective disorder . There is only limited information available on the use of aripiprazole in children and adolescents , and pilot data suggest that a revised dosing strategy , based on weight , is indicated in this population . In the long-term studies , the use of aripiprazole was associated with continued efficacy , good compliance and increased time-to-relapse . Aripiprazole represents the first functionally selective atypical antipsychotic drug . Rikkunshito , a Kampo medicine , ameliorates post-operative ileus by anti-inflammatory action . Rikkunshito ( RKT ) , a Kampo ( Japanese herbal ) medicine , is used as a prokinetic for patients with various diseases including functional dyspepsia . RKT promotes delayed gastric emptying via 5- Q9H205 receptor blockade . Otherwise , RKT increases ghrelin release via P41595 and P28335 receptor activation . Recent studies revealed that ghrelin and 5- Q9H205 receptor antagonists have an anti-inflammatory effect . So we hypothesize that RKT may have an anti-inflammatory action in the post-operative ileus . Intestinal manipulation ( IM ) was applied to the distal ileum of mice . RKT was administered orally 4 times before and after IM . Gastrointestinal transit in vivo , leukocyte infiltration , and gastric emptying were analyzed . We also investigated the effects of the 5- Q9H205 receptor agonist m-chlorophenylbiguamide ( mCPBG ) and ghrelin-receptor antagonist [ D-Lys3 ] - Q92847 -6 on the ameliorative action of RKT . RKT treatment led to recovery of the delayed intestinal transit and gastric emptying rate induced by IM . RKT significantly inhibited the infiltration of neutrophils and macrophages . [ D-Lys3 ] - Q92847 -6 reduced and mCPBG partially reduced the RKT-mediated anti-inflammatory activity , as monitored by infiltrating macrophages and neutrophils . RKT serves as a novel therapeutic agent for POI characterized by its anti-inflammatory potency , in addition to prokinetic action . The RKT-induced anti-inflammatory activity may be partly mediated by inhibition of the 5- Q9H205 receptor and ghrelin release . The anti-androgen drug dutasteride renders triple negative breast cancer cells more sensitive to chemotherapy via inhibition of HIF-1α-/ P15692 -signaling . BACKGROUND : Triple negative breast cancer ( TNBC ) is characterized by lack of expression of both estrogen and progesterone receptor as well as lack of amplification of P04626 . Patients with TNBC carry an unfavorable prognosis compared to other breast cancer subtypes given that endocrine or P04626 targeted therapies are not effective , rendering chemotherapy the sole effective treatment option to date . Therefore , there is a high demand for additional novel treatment options . FINDINGS : We previously published a list of genes showing both higher gene expression rates in TNBC and , in addition , are known to encode targets of non-oncologic drugs . P18405 , which encodes the type-1 isoform of the steroid-5alpha-reductase , which is involved in androgen metabolism , was found to be one of these genes . DB01126 is a dual blocker of both the type-1 and type-2 isoform of P18405 and is indicated in the treatment of benign prostate hyperplasia . Treatment of TNBC cell lines with dutasteride was associated with a dose-dependent decrease in cell viability , altered protein expression of P15692 and HIF-1α and increased chemosensitivity . CONCLUSION : Our results demonstrate that the P18405 -corresponding anti-androgenic drug dutasteride might act as a combinatorial therapeutic option besides standard chemotherapy in highly aggressive TNBC . [ Influence of serotonergic transmission on response to olanzapine ] . INTRODUCTION : This study aimed to investigate associations between the response to olanzapine and genetic variations ( polymorphisms ) in serotonergic transmission related genes in a sample of prospectively studied schizophrenic patients treated with this drug . METHODOLOGY : A total of 51 non-related patients with a DSM-IV diagnosis of schizophrenia were treated with olanzapine ( mean dose : 12 mg/day ; range : 5-25 mg ) and followed-up for at least three months . Response to olanzapine was measured by the difference between baseline and post-treatment scores on the PANSS and GAS scales . The following polymorphisms were studied : serotonin receptor 5- Q13049 ( 102-T/C , His452Tyr ) , serotonin receptor P28335 ( Cys23Ser , -330- P19440 /-244-CT ) , and serotonin transporter ( VNTR , 5-HTTLPR ) . RESULTS : Global clinical improvement , measured with both the GAS and PANSS total scores , was observed . When patients were divided into responders and non-responders , the distribution of genotypic and allelic frequencies was similar to the one observed in previous studies with clozapine . When regression analyses were undertaken , polymorphism 330-GT/-244-CT of the P28335 serotonin receptor and 5-HTTLPR of the serotonin transporter showed a tendency towards the association to olanzapine response . CONCLUSIONS : The present study provides preliminary evidence of the important role of variations in serotonin transmission related genes in determining clinical response to olanzapine . Considering previous studies , it can also be concluded that olanzapine and clozapine may have similar affinities to serotonin receptors . Ca2+-calmodulin and janus kinase 2 are required for activation of sodium-proton exchange by the Gi-coupled 5-hydroxytryptamine 1a receptor . The type 1 sodium-proton exchanger ( P19634 ) is expressed ubiquitously and regulates key cellular functions , including mitogenesis , cell volume , and intracellular pH . Despite its importance , the signaling pathways that regulate P19634 remain incompletely defined . In this work , we present evidence that stimulation of the 5-hydroxytryptamine 1A ( P08908 ) receptor results in the formation of a signaling complex that includes activated O60674 ( Jak2 ) , Ca2+/calmodulin ( P62158 ) , and P19634 , and which involves tyrosine phosphorylation of P62158 . The signaling pathway also involves rapid agonist-induced association of P62158 and P19634 as assessed by coimmunoprecipitation studies and by bioluminescence resonance energy transfer studies in living cells . We propose that P19634 is activated through this pathway : P08908 receptor --> G(i2)alpha and/or G(i3)alpha --> Jak2 activation --> tyrosine phosphorylation of P62158 --> increased binding of P62158 to P19634 --> induction of a conformational change in P19634 that unmasks an obscured proton-sensing and/or proton-transporting region of P19634 --> activation of P19634 . The G(i/o)-coupled P08908 receptor now joins a handful of Gq-coupled receptors and hypertonic shock as upstream activators of this emerging pathway . In the course of this work , we have presented clear evidence that P62158 can be activated through tyrosine phosphorylation in the absence of a significant role for elevated intracellular Ca2+ . We have also shown for the first time that the association of P62158 with P19634 in living cells is a dynamic process . DB00160 aminotransferase homologs catalyze the glutamate:glyoxylate aminotransferase reaction in peroxisomes of Arabidopsis . Plant peroxisomal glyoxylate aminotransferases play central roles within the photorespiratory pathway . Genes encoding glyoxylate aminotransferases have been isolated from several animals and microbes , but only recently have plant homologs been identified . Three Arabidopsis homologs of alanine (Ala):glyoxylate aminotransferase 2 ( Q9BYV1 ) contain a putative type 1 peroxisomal targeting signal ( PTS1 ) , but the metabolic significance of these Q9BYV1 homologs is unknown . P19440 and P36268 are Ala aminotransferase ( AlaAT ) homologs from Arabidopsis that represent another type of glyoxylate aminotransferase . These proteins are class I aminotransferases , each containing a putative PTS1 . P19440 and P36268 are members of a small family of AlaATs in Arabidopsis . When expressed as recombinant proteins in Escherichia coli , P19440 and P36268 displayed biochemical characteristics very similar to one another , and to the Arabidopsis protein purified from leaves . Four aminotransferase activities were specifically associated with P19440 and P36268 , using the substrate pairs glutamate ( DB00142 ):glyoxylate , Ala:glyoxylate , DB00142 :pyruvate , and Ala:2-oxoglutarate . P19440 and P36268 may have partially redundant functions ; transcripts of both genes were detected in many of the same tissues . Although DB00142 :glyoxylate aminotransferase ( P19440 ) activity has been observed in several locations in different plants and algae , including the cytoplasm and mitochondria , our subcellular fractionation data indicate that P19440 activity was exclusively peroxisomal in Arabidopsis . Thus , glyoxylate aminotransferase reactions in plant peroxisomes appear to be catalyzed by at least two distinct types of aminotransferases : an AGT1 homolog with serine:glyoxylate aminotransferase activity ( A.H. Liepman , L.J. Olsen [ 2001 ] Plant J 25 : 487-498 ) , and a pair of closely related , potentially redundant AlaAT homologs with P19440 activity . Allele C-specific methylation of the 5- Q13049 receptor gene : evidence for correlation with its expression and expression of DNA methylase P26358 . Differential DNA methylation has been suggested to contribute to differential activity of alleles C and T and thereby to genetic associations between the C/T(102) polymorphism in the 5- Q13049 receptor gene ( 5HT2AR ) and psychiatric disorders . We surveyed methylation in two CpG sites , which are specific to allele C . The majority of allele C-specific CpG sites were methylated in human temporal cortex and peripheral leukocytes and levels of methylation varied between individuals . Levels of methylation in the promoter correlated significantly with the expression of 5HT2AR . Methylation of allele C-specific CpG sites in the first exon correlated significantly with the expression of DNA methylase 1 ( P26358 ) but not S-adenosylhomocysteine hydrolase ( P23526 ) . These findings support the hypothesis that allele-specific DNA methylation is involved in regulation of 5HT2AR expression , influencing expression differences between alleles C and T . 8-OH-DPAT ( P08908 agonist ) Attenuates 6-Hydroxy- dopamine-induced catalepsy and Modulates Inflammatory Cytokines in Rats . OBJECTIVE(S) : Neuroinflammation in Parkinson disease ( PD ) is associated with glial cells activation and production of different inflammatory cytokines . In this study , we investigated the effect of chronic administration of 8-OH-DPAT on 6-OHDA-induced catalepsy and levels of inflammatory cytokines in cerebrospinal fluid ( P04141 ) . MATERIALS AND METHODS : Catalepsy was induced by unilateral infusion of 6-OHDA ( 8 μg/2 μl/rat ) into the central region of the sabstantia nigra pars compacta ( SNc ) being assessed by the bar-test , 5 , 60 , 120 and 180 min after intraperitoneal ( IP ) administration of 8-OH-DPAT ( P08908 receptor agonist ; 0.25 , 0.5 and 1mg/kg , IP for 10 days ) . P04141 samples were collected on the tenth day of 8-OH-DPAT administration and analyzed by ELISA method to measure levels of P01375 -α , IL-1β and P05231 . RESULTS : Chronic injection of 8-OH-DPAT decreased catalepsy in a dose dependent manner when compared with the control group . The most anti-cataleptic effect was observed at the dose of 1 mg/kg of 8-OH-DPAT . Levels of P01375 -α in P04141 increased three weeks after 6-OHDA injection while there was a significant decrease in P01375 -α level of parkinsonian animals treated with 8-OH-DPAT ( 1 mg/kg , IP for 10 days ) . IL-1β and P05231 decreased and increased in parkinsonian rats and in 8-OH-DPAT-treated parkinsonian rats , respectively . CONCLUSION : Our study indicated that chronic administration of 8-OH-DPAT improves catalepsy in 6-OHDA-induced animal model of PD and restores central concentration of inflammatory cytokines to the basal levels . P08908 receptor agonists can be suggested as potential adjuvant therapy in PD by modulation of cerebral inflammatory cytokines .