Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0282612 (PIN)
 2,291 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The beta-adrenergic receptors (beta-ARs) coupled to pepsinogen secretion on frog esophageal peptic cells have been compared to frog erythrocyte beta-ARs using the radioligand 125I-iodopindolol (125I-PIN). 125I-PIN binding to intact peptic cells was time and temperature dependent. Saturation and competition experiments established that a large component of this binding represented radioligand uptake, which was energy dependent, pH sensitive, Na+ independent, and inhibited by agents that depress cellular ATP or disrupt proton gradients. This uptake system, which was absent from frog erythrocytes, appeared similar to that recently described for a number of mammalian cells. 125I-PIN bound to a single class of sites on peptic cell homogenates with a KD = 64 (+/- 5) pM. Binding to cell homogenates and a proportion of the binding to intact cells was inhibited by beta-agonists and antagonists with pharmacological characteristics similar to typical beta 2-ARs of frog erythrocytes. The number of beta-ARs in these peptic cell preparations was 1300 (+/- 240) sites/cell. Isolated peptic cells were poorly responsive to isoproterenol stimulation even in the presence of the phosphodiesterase inhibitor IBMX (3-isobutyl-1-methylxanthine). Pretreatment of cells with the phorbol ester TPA (12-O-tetra-decanoylphorbol-13-acetate) (100 nM) promoted isoproterenol stimulation of pepsinogen secretion. Catecholamine agonists stimulated pepsinogen secretion with an order of potency: isoproterenol greater than epinephrine much greater than norepinephrine, which was identical to that determined for inhibition of 125I-PIN binding. These findings indicate that frog peptic cells contain beta 2-ARs functionally coupled to pepsinogen secretion.
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PMID:125I-iodopindolol binding to frog esophageal peptic cells. Detection of amine uptake and beta-adrenergic receptors coupled to pepsinogen secretion. 254 27

The 119-amino acid residue prolyl cis/trans isomerase from Arabidopsis thaliana (PIN1At) is similar to the catalytic domain of the human hPIN1. However, PIN1At lacks the N-terminal WW domain that appears to be essential for the hPIN1 function. Here, the solution structure of PIN1At was determined by three-dimensional nuclear magnetic resonance spectroscopy. The PIN1At fold could be superimposed on that of the catalytic domain of hPIN1 and had a 19 residue flexible loop located between strand beta1 and helix alpha1. The dynamical features of this beta1/alpha1-loop, which are characteristic for a region involved in protein-protein interactions, led to exchange broadening in the NMR spectra. When sodium sulfate salt was added to the protein sample, the beta1/alpha1 loop was stabilized and, hence, a complete backbone resonance assignment was obtained. Previously, with a phospho-Cdc25 peptide as substrate, PIN1At had been shown to catalyze the phosphoserine/phosphothreonine prolyl cis/trans isomerization specifically. To map the catalytic site of PIN1At, the phospho-Cdc25 peptide or sodium sulfate salt was added in excess to the protein and chemical shift changes in the backbone amide protons were monitored in the (1)H(N)-(15)N heteronuclear single quantum coherence spectrum. The peptide caused perturbations in the loops between helix alpha4 and strand beta3, between strands beta3 and beta4, in the alpha3 helix, and in the beta1/alpha1 loop. The amide groups of the residues Arg21 and Arg22 showed large chemical shift perturbations upon phospho-Cdc25 peptide or sulfate addition. We conclude that this basic cluster formed by Arg21 and Arg22, both located in the beta1/alpha1 loop, is homologous to that found in the hPIN1 crystal structure (Arg68 and Arg69), which also is involved in sulfate ion binding. We showed that the sulfate group competed for the interaction between PIN1At and the phospho-Cdc25 peptide. In the absence of the WW domain, three hydrophobic residues (Ile33, Ile34, and Leu35) located in the long flexible loop and specific for the plant PIN-type peptidyl prolyl cis/trans isomerases (PPIases) could be an additional interaction site in PIN1At. However, phospho-peptide addition did not affect the resonances of these residues significantly. Electrostatic potential calculations revealed a negatively charged area not found in hPIN1 on the PIN1At molecular surface, which corresponds to the surface shielded by the WW domain in hPIN1. Based on our experimental results and the molecular specificities of the PIN1At enzyme, functional implications of the lack of WW domains in this plant PIN-type PPIase will be discussed.
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PMID:Solution structure of the single-domain prolyl cis/trans isomerase PIN1At from Arabidopsis thaliana. 1207 89

Puroindolines are endosperm lipid binding proteins, which are separated by reversed phase-high-performance liquid chromatography or cation exchange chromatography into two isoforms, puroindoline-a (PIN-a) and puroindoline-b (PIN-b). Being very basic and close in molecular weight, PIN-a and PIN-b have never been separated using conventional isoelectric focusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). A two-dimensional electrophoresis method, linear immobiline pH gradient (IPGxSDS-PAGE), was developed, using 6-11 linear immobiline Dry Strips in the first dimension, which allowed the puroindolines to be focused between isoelectric point 10.5 and 11. Immunoblotting revealed that both PIN-a and PIN-b were each composed of several spots. Two-dimensional patterns from unrelated wheat varieties revealed that several spots can be highlighted among varieties. Matrix-assisted laser desorption/ionization-time of flight spectrometry allowed the majority of the spots revealed in the puroindoline zone to be identified. The two-dimensional IPGxSDS-PAGE of these very basic wheat endosperm proteins, puroindolines and related grain softness proteins should facilitate the identification of the proteins associated with wheat endosperm texture that have a strong effect on milling, dough properties and end-uses of wheats.
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PMID:Diversity of puroindolines as revealed by two-dimensional electrophoresis. 1260 9

Prions are infectious, self-propagating protein conformations. Rnq1 is required for the yeast Saccharomyces cerevisiae prion [PIN(+)], which is necessary for the de novo induction of a second prion, [PSI(+)]. Here we isolated a [PSI(+)]-eliminating mutant, Rnq1Delta100, that deletes the nonprion domain of Rnq1. Rnq1Delta100 inhibits not only [PSI(+)] prion propagation but also [URE3] prion and huntingtin's polyglutamine aggregate propagation in a [PIN(+)] background but not in a [pin(-)] background. Rnq1Delta100, however, does not eliminate [PIN(+)]. These findings are interpreted as showing a possible involvement of the Rnq1 prion in the maintenance of heterologous prions and polyQ aggregates. Rnq1 and Rnq1Delta100 form a sodium dodecyl sulfate-stable and Sis1 (an Hsp40 chaperone protein)-containing coaggregate in [PIN(+)] cells. Importantly, Rnq1Delta100 is highly QN-rich and prone to self-aggregate or coaggregate with Rnq1 when coexpressed in [pin(-)] cells. However, the [pin(-)] Rnq1-Rnq1Delta100 coaggregate does not represent a prion-like aggregate. These findings suggest that [PIN(+)] Rnq1-Rnq1Delta100 aggregates interact with other transmissible and nontransmissible amyloids to destabilize them and that the nonprion domain of Rnq1 plays a crucial role in self-regulation of the highly reactive QN-rich prion domain of Rnq1.
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PMID:A regulatory role of the Rnq1 nonprion domain for prion propagation and polyglutamine aggregates. 1833 19

The microelectrode array (MEA) was used to evaluate the cardioprotective effects of adenosine triphosphate sensitive potassium (K(ATP)) channel activation using potassium channel openers (KCOs) on HL-1 cardiomyocytes subjected to acute chemically induced metabolic inhibition. Beat frequency and extracellular action potential (exAP) amplitude were measured in the presence of metabolic inhibitors (sodium azide (NaN(3)) or 2-deoxyglucose (2-DG)) or KCOs (pinacidil (PIN, a cyanoguanidine derivative, activates sarcolemmal K(ATP) channels) or SDZ PCO400 (SDZ, a benzopyran derivative, activates mitochondrial K(ATP) channels)). The protective effects of these KCOs on metabolically inhibited HL-1 cells were subsequently investigated. Signal shapes indicated that NaN(3) and 2-DG reduced the rate of the sodium (Na(+)) influx signal as reflected by a reduction in beat frequency. PIN and SDZ appeared to reduce both rate of depolarization and extent of the Na(+) influx signals. Pre-treating cardiomyocytes with PIN (0.1 mM), but not SDZ, prevented the reduction of beat frequency associated with NaN(3)- or 2-DG-induced metabolic inhibition. The exAP amplitude was not affected by either KCO. The cardioprotective effect of PIN relative to SDZ may be due to the opening of different K(ATP) channels. This metabolic inhibition model on the MEA may provide a stable platform for the study of cardiac pathophysiology in the future.
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PMID:The use of microelectrode array (MEA) to study the protective effects of potassium channel openers on metabolically compromised HL-1 cardiomyocytes. 1913 34

We present in this paper a dedicated home-built RF probe-head for the MRI of rat brain at 2.35 T. This probe consists of an association of three coils: a double-tuned birdcage coil, which could be used for both transmitting and receiving, and a single-tuned surface coil that is used for the only receiving. This single-tuned coil is actively decoupled from the double-tuned volume coil. The active decoupling is based on the pole insertion technique using PIN diodes circuitry. This development was initially motivated by its potential and future application to the brain perfusion measurements by the MRI of hyperpolarized xenon-129 (HP (129)Xe). However, one of underlying ideas behind this work is to proceed well beyond this specific application. Particularly, the developed coil could also be dedicated for the sodium-23 ((23)Na) MRI in the rat brain. Indeed we tried to make the design versatile, simple and easy to replicate by other research groups, with a low cost, minimum development time and accepted performances. We believe that this design could by useful for groups who consider building own hardware. This is why we describe in some details the practical aspects of the workbench design as well as the coil characterization. For simplicity reasons, the first results of developed prototype were obtained at 100 MHz and 26.4 MHz (proton and sodium-23 frequencies at 2.35 T). MR images of phantoms were realized. In-vivo (1)H images and (23)Na spectra of the rat brain were also obtained. Future validation would concern the MRI of HP (129)Xe.
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PMID:A three-coil RF probe-head at 2.35 T: Potential applications to the (23)Na and to the hyperpolarized (129)Xe MRI in small animals. 2109 20

Nitric oxide (NO) is considered a key regulator of plant developmental processes and defense, although the mechanism and direct targets of NO action remain largely unknown. We used phenotypic, cellular, and genetic analyses in Arabidopsis thaliana to explore the role of NO in regulating primary root growth and auxin transport. Treatment with the NO donors S-nitroso-N-acetylpenicillamine, sodium nitroprusside, and S-nitrosoglutathione reduces cell division, affecting the distribution of mitotic cells and meristem size by reducing cell size and number compared with NO depletion by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO). Interestingly, genetic backgrounds in which the endogenous NO levels are enhanced [chlorophyll a/b binding protein underexpressed 1/NO overproducer 1 (cue1/nox1) mirror this response, together with an increased cell differentiation phenotype. Because of the importance of auxin distribution in regulating primary root growth, we analyzed auxin-dependent response after altering NO levels. Both elevated NO supply and the NO-overproducing Arabidopsis mutant cue1/nox1 exhibit reduced expression of the auxin reporter markers DR5pro:GUS/GFP. These effects were accompanied by a reduction in auxin transport in primary roots. NO application and the cue1/nox1 mutation caused decreased PIN-FORMED 1 (PIN1)-GFP fluorescence in a proteasome-independent manner. Remarkably, the cue1/nox1-mutant root phenotypes resemble those of pin1 mutants. The use of both chemical treatments and mutants with altered NO levels demonstrates that high levels of NO reduce auxin transport and response by a PIN1-dependent mechanism, and root meristem activity is reduced concomitantly.
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PMID:Nitric oxide causes root apical meristem defects and growth inhibition while reducing PIN-FORMED 1 (PIN1)-dependent acropetal auxin transport. 2202 39

Influence of selenium on induced carcinogenesis of the prostate and other organs was studied in male Wistar rats. Carcinogenesis was induced (68) by using our modification of a combined double-stage model including surgical castration, single administration of N-methyl-N-nitrosourea (MNU) and long-term promotion by a mix of testosterone ethers (MTE). Seven days after MNU injection the rats were randomized to form 2 groups. Controls were fed drinking water while the study group - water containing sodium selenite 4mg/l, daily - till the end of the experiment. Controls (12) were not exposed to any treatment. They were followed up for 55 weeks until sacrificed. Apparent benign prostatic hyperplasia developed in rats subjected to castration, MNU and MTE. Also, such precancerous lesions as prostatic intraepithelial neoplasia (PIN) and prostate cancer including metastatic one were detected. Malignant lymphoma, other than in target tissues, was the most frequent. Prostate pathological changes and lymphomas were not registered in intact rats. Unlike rats treated with MNU and MTE and fed untreated drinking water, selenium did not influence significantly the development of prostate intraepithelial neoplasia but reduced multiplicity of prostate cancer by 44.6%. Simultaneously, the incidence of induced malignant lymphomas decreased by 26.4%.
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PMID:[Influence of sodium selenite on carcinogenesis of the prostate and other organs induced by methylnitrosourea and testosterone in rats]. 2219 Dec 39

The critical design aim for a sodium/proton coil is to maximize sodium sensitivity and transmit field homogeneity while simultaneously providing adequate proton sensitivity and homogeneity. While most dual-frequency coils use lossy high-impedance trap circuits or PIN diodes to allow dual-resonance, we explored a nested-coil design for sodium/proton knee imaging at 7 T. A stand-alone eight-channel sodium receive array was implemented without standard dual-resonance circuitry to provide improved sodium signal-to-noise ratio. A detunable sodium birdcage was added for homogeneous sodium excitation and a four-channel proton transmit-receive array was added to provide anatomical reference imaging and B0 shimming capabilities. Both additional modules were implemented with minimal disturbance to the eight-channel sodium array by managing their respective resonances and geometrical arrangement. In vivo sodium signal-to-noise ratio was 1.2-1.7 times greater in the developed eight-channel array than in a mononuclear sodium birdcage coil, whereas the developed four-channel proton array provided signal-to-noise ratio similar to that of a commercial mononuclear proton birdcage coil.
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PMID:Design of a nested eight-channel sodium and four-channel proton coil for 7T knee imaging. 2288 23

Impaired Ca2+ signaling in prostate cancer contributes to several cancer hallmarks, such as enhanced proliferation and migration and a decreased ability to induce apoptosis. Na+ influx via transient receptor potential melastatin 4 channel (TRPM4) can reduce store-operated Ca2+ entry (SOCE) by decreasing the driving force for Ca2+. In patients with prostate cancer, gene expression of TRPM4 is elevated. Recently, TRPM4 was identified as a cancer driver gene in androgen-insensitive prostate cancer.We investigated TRPM4 protein expression in cancer tissue samples from 20 patients with prostate cancer. We found elevated TRPM4 protein levels in prostatic intraepithelial neoplasia (PIN) and prostate cancer tissue compared to healthy tissue. In primary human prostate epithelial cells (hPEC) from healthy tissue and in the androgen-insensitive prostate cancer cell lines DU145 and PC3, TRPM4 mediated large Na+ currents. We demonstrated significantly increased SOCE after siRNA targeting of TRPM4 in hPEC and DU145 cells. In addition, knockdown of TRPM4 reduced migration but not proliferation of DU145 and PC3 cells. Taken together, our data identify TRPM4 as a regulator of SOCE in hPEC and DU145 cells, demonstrate a role for TRPM4 in cancer cell migration and suggest that TRPM4 is a promising potential therapeutic target.
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PMID:Transient receptor potential melastatin 4 channel contributes to migration of androgen-insensitive prostate cancer cells. 2649 25


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