Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We tested the hypothesis that activation of Rho-A-dependent kinase (ROCK-II) alters cardiac myofilament response to Ca2+ by mechanisms involving phosphorylation of thin filament proteins. We determined effects of a constitutively active form of ROCK-II on ATPase activity and tension development in detergent-extracted (skinned) fiber bundles isolated from mouse left ventricular papillary muscles. ROCK-II induced a depression in maximum ATPase rate and tension, which was associated with phosphorylation of troponin T (TnT), troponin I (TnI), and myosin-binding protein C (C-protein). This effect of ROCK-II was retained in fiber bundles isolated from transgenic (TG) mice in which phosphorylation sites (S14, S15, and S19) of myosin light chain 2 were mutated to alanine. Moreover, exchange of ROCK-II-phosphorylated Tn complex with the native Tn complex in the fiber bundles resulted in inhibition of maximal Ca2+ activation of tension and ATPase activity. Mass spectrometric analysis demonstrated that ROCK-II phosphorylated cardiac TnI (cTnI) at S23, S24, and T144 and cardiac TnT (cTnT) at S278 and T287. An important role for these cTnT sites is indicated by results demonstrating that ROCK-II induced a depression in tension and ATPase activity in skinned fiber bundles from a TG model in which cTnI is replaced by slow skeletal TnI, which lacks S23 and S24 and in which T144 is replaced by proline. Our data provide the first evidence that ROCK-II phosphorylation of the Tn complex, most likely at cTnT, has an important role in functional effects of signaling through the Rho-A pathway.
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PMID:Functional effects of rho-kinase-dependent phosphorylation of specific sites on cardiac troponin. 1577 59

Poly(L-valine-L-proline-L-alanine-L-valine-L-glycine) (VPAVG) is a new kind of proteinaceous polymer belonging to the Elastin-like family. These polymers are based on the recurrence of certain short peptide monomers that are considered as "building blocks" in the natural elastin. This smart thermoresponsive polymer has the ability to self-associate at physiological temperature to form aggregates with about 60% in water. This ability can be harnessed to prepare microparticles loaded with an active substance. The aim of this report is to evaluate, from the results of the experiment conducted, the biocompatibility of microparticles prepared from poly(VPAVG). We have studied the cytotoxic effects of microparticles, edema formation after subcutaneous injection (1 and 2.5 mg) in rats (n = 6), and also intraocular tolerance after the intravitreal injection of 2.5 mg of poly(VPAVG) microparticles into pigmented rabbits (n = 12). The polymer did not induce any cytotoxicity or nonspecific depression of cellular respiration on macrophages under the range of polymer concentrations investigated in this study (20, 30, 40, and 60 mg/mL). We observed no inflammatory response to microparticles after subcutaneous injection in the hind-paw of rats, with no significant differences between the control group (PBS) and experimental groups. Anterior and posterior segment signs were evaluated after intraocular injection of poly(VPAVG) microparticles. Only a few eyes (2/11) of the experimental group presented inflammation signs at day 28 postinjection. Nevertheless, 45% (5/11) of the eyes receiving microparticles showed tractional retinal detachment. The results observed in this work suggested certain fibroblastic activity induced by poly(VPAVG) microparticles after their intraocular injection.
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PMID:Biocompatibility of elastin-like polymer poly(VPAVG) microparticles: in vitro and in vivo studies. 1664 66

The glycine-rich antifreeze protein recently discovered in snow fleas exhibits strong freezing point depression activity without significantly changing the melting point of its solution (thermal hysteresis). BLAST searches did not detect any protein with significant similarity in current databases. Based on its circular dichroism spectrum, discontinuities in its tripeptide repeat pattern, and intramolecular disulfide bonding, a detailed theoretical model is proposed for the 6.5-kDa isoform. In the model, the 81-residue protein is organized into a bundle of six short polyproline type II helices connected (with one exception) by proline-containing turns. This structure forms two sheets of three parallel helices, oriented antiparallel to each other. The central helices are particularly rich in glycines that facilitate backbone carbonyl-amide hydrogen bonding to four neighboring helices. The modeled structure has similarities to polyglycine II proposed by Crick and Rich in 1955 and is a close match to the polyproline type II antiparallel sheet structure determined by Traub in 1969 for (Pro-Gly-Gly)(n). Whereas the latter two structures are formed by intermolecular interactions, the snow flea antifreeze is stabilized by intramolecular interactions between the helices facilitated by the regularly spaced turns and disulfide bonds. Like several other antifreeze proteins, this modeled protein is amphipathic with a putative hydrophobic ice-binding face.
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PMID:Structural modeling of snow flea antifreeze protein. 1715 62

Twenty rhizobacterial strains containing 1-aminocyclopropane-1-carboxylate deaminase were isolated from the rhizosphere of salt-affected maize fields. They were screened for their growth-promoting activities under axenic conditions at 1, 4, 8, and 12 dS x m-1 salinity levels. Based upon the data of the axenic study, the 6 most effective strains were selected to conduct pot trials in the wire house. Besides one original salinity level (1.6 dS x m-1), 3 other salinity levels (4, 8, and 12 dS x m-1) were maintained in pots and maize seeds inoculated with selected strains of plant growth-promoting rhizobacteria, as well as uninoculated controls were sown. Results showed that the increase in salinity level decreased the growth of maize seedlings. However, inoculation with rhizobacterial strains reduced this depression effect and improved the growth and yield at all the salinity levels tested. Selected strains significantly increased plant height, root length, total biomass, cob mass, and grain yield up to 82%, 93%, 51%, 40%, and 50%, respectively, over respective uninoculated controls at the electrical conductivity of 12 dS x m-1. Among various plant growth-promoting rhizobacterial strains, S5 (Pseudomonas syringae), S14 (Enterobacter aerogenes), and S20 (Pseudomonas fluorescens) were the most effective strains for promoting the growth and yield of maize, even at high salt stress. The relatively better salt tolerance of inoculated plants was associated with a high K+/Na+ ratio as well as high relative water and chlorophyll and low proline contents.
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PMID:Preliminary investigations on inducing salt tolerance in maize through inoculation with rhizobacteria containing ACC deaminase activity. 1802 6

Prolyl oligopeptidase (POP) is a serine endopeptidase which hydrolyzes proline-containing peptides shorter than 30 amino acids. It has been suggested that POP is associated with cognitive functions, possibly via the cleavage of neuropeptides such as substance P (SP). Recently, several studies have also linked POP to the inositol 1,4,5-triphosphate (IP(3)) signaling. However, the neuroanatomical interactions between these substances are not known. We used double-labeled immunofluorescence to determine the POP colocalization with SP, SP receptor (neurokinin-1 receptor, NK-1R) and IP(3) type 1 receptor (IP(3)R1) in the rat brain. Furthermore, since striatal and cortical GABAergic neurons are involved in SP neurotransmission, we studied the coexpression of POP, SP and GABA by triple-labeled immunofluorescence. POP was moderately present in IP(3)R1-containing cells in cortex; the colocalization was particularly high in the thalamus, hippocampal CA1 field and cerebellar Purkinje cells. Colocalization of POP with SP and NK1-receptor was infrequent throughout the brain, though some POP and SP coexpression was observed in cerebellar Purkinje cells. We also found that POP partially colocalized with SP-containing GABAergic neurons in striatum and cortex. Our findings support the view that POP is at least spatially associated with the IP(3)-signaling in the thalamus, hippocampus and cerebellar Purkinje cells. This might point to a role for POP in the regulation of long-term potentiation and/or depression. Moreover, the low degree of colocalization of POP, SP and its NK-1R suggests that a transport system is needed either for POP or SP to make hydrolysis possible and that POP may act both intra- and extracellularly.
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PMID:Spatial association of prolyl oligopeptidase, inositol 1,4,5-triphosphate type 1 receptor, substance P and its neurokinin-1 receptor in the rat brain: an immunohistochemical colocalization study. 1845 82

Arginase (amidinohydrolase, EC 3.5.3.1) is known as the last enzyme in the urea cycle in the liver, but it is also present in extrahepatic tissues. Arginase hydrolyzes L-arginine to L-ornithine and urea and its biochemical and physiological role varies depending on the organism and tissue. Besides its participation in ammonia detoxification, arginase is involved in the synthesis of polyamines, crucial for the proper course of many metabolic processes, proline, the main connective tissues protein, and glutamates, amino acids which take part in nitric metabolism, important in the nervous system and also a substrate for protein synthesis. The competition of arginase with nitric oxide synthase (NOS) for the common substrate L-arginine indicates its participation in the regulation of nitric oxide (NO) synthesis. The physiological role of arginase and its common occurrence indicate its engagement in many pathologies. Due to its competition with NOS for arginine and its participation in proline synthesis, arginase plays an important role in such diseases as cerebral stroke, trauma, inflammation, and depression, whereas its participation in polyamine synthesis indicates arginase's engagement in the development of neoplastic diseases in the human organism.
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PMID:[New insights into arginase. Part II. Role in physiology and pathology]. 1848 Jul 37

The effects of acute and chronic stress on the production of systemic metabolites were investigated in male Sprague-Dawley (SD) rats. Metabolites excreted in urine were analyzed using GC/MS in conjunction with multivariate and univariate statistical techniques. SD rats were subjected to two kinds of acute stress and chronic unpredictable mild stress, respectively. Metabolic analysis demonstrated that urinary expression of a number of metabolites including glutamate, glutamine, homovanillate, proline, succinate, citrate, and tyrosine altered in the acute stress model in the same way as in the chronic model, while pimelate and hippurate changed in the opposite trend. The results suggested that the stress induced metabolic perturbations were reversible and nonspecific. Metabolic response to chronic combined stress revealed biochemical clues to depression-like symptoms validated by behavior and physiologic results. This study provides a noninvasive and dynamic analytical strategy for the characterization of endogenous metabolic perturbations induced by external stress.
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PMID:Metabonomics approach to understanding acute and chronic stress in rat models. 1929

We investigated a carbohydrate-rich nutrient-drink mix for treatment of seasonal affective disorder (SAD). This mixture may contribute to brain serotonin synthesis, potentially exerting an antidepressant effect and controlling carbohydrate cravings. Two successive double-blind placebo-controlled studies were performed. In Study 1, 18 subjects (50% women; mean age 43 +/- 15 years) with SCID-diagnosed SAD were randomized to 12 days of twice daily carbohydrate beverage (CHO) containing mixed starches, or a placebo beverage (PRO) containing the CHO mix plus casein protein to dampen serotonin synthesis. Following a 2-day washout, subjects were crossed over to the other treatment for 12 days. In Study 2, 32 subjects (63% women; mean age 46 +/- 14 years) with SCID-diagnosed SAD were randomized to 21 days of CHO or PRO. Efficacy in both studies was determined by the first 17 items of the Hamilton Depression Rating Scale (HAM-D-28), an appetite questionnaire, and regular weighing. In Study 1, response rates were 50% for both groups. Remission rates favored CHO (50% vs. 38%), as did the decrease in the HAM-D-17 score, but differences were nonsignificant. In Study 2, response rates were 71% for CHO and 76% for PRO, and remission rates were 71% for each group. Both treatment groups experienced significant improvement in HAM-D-17 scores within 1 week of treatment, which continued through the entire study period. Weight change did not differ significantly between treatment groups in either study. The drink mix was well tolerated and treatment adherence was high. Both the active and placebo intervention were effective in alleviating symptoms of SAD. Replication studies in larger samples appear warranted.
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PMID:Report of two double-blind randomized placebo-controlled pilot studies of a carbohydrate-rich nutrient mixture for treatment of seasonal affective disorder (SAD). 2007 Jul 85

Prolyl peptidases cleave proteins at proline residues and are of importance for cancer, neurological function, and type II diabetes. Prolyl endopeptidase (PEP) cleaves neuropeptides and is a drug target for neuropsychiatric diseases such as post-traumatic stress disorder, depression, and schizophrenia. Previous structural analyses showing little differences between native and substrate-bound structures have suggested a lock-and-key catalytic mechanism. We now directly demonstrate from seven structures of Aeromonus punctata PEP that the mechanism is instead induced fit: the native enzyme exists in a conformationally flexible opened state with a large interdomain opening between the beta-propeller and alpha/beta-hydrolase domains; addition of substrate to preformed native crystals induces a large scale conformational change into a closed state with induced-fit adjustments of the active site, and inhibition of this conformational change prevents substrate binding. Absolute sequence conservation among 28 orthologs of residues at the active site and critical residues at the interdomain interface indicates that this mechanism is conserved in all PEPs. This finding has immediate implications for the use of conformationally targeted drug design to improve specificity of inhibition against this family of proline-specific serine proteases.
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PMID:Induced-fit mechanism for prolyl endopeptidase. 2044 88

Prolyl oligopeptidase or prolyl endopeptidase (PREP; EC 3.4.21.26) is an atypical serine protease that hydrolyses peptides and peptide hormones after proline in peptides up to around 30 residues long. Evidence suggests an involvement in learning and memory, and the enzyme is implicated in diseases including amnesia and depression. The first crystal structures determined, of the porcine enzyme, provided direct insight into the mechanisms of substrate size selectivity, substrate specificity, and catalysis. However in these structural studies the enzyme is in a closed state, even in the absence of ligand, leaving questions as to how substrates and products can enter and exit the enclosed central cavity that houses the active site. More recent crystal structures of bacterial PREP have captured the enzyme in an open state, revealing the true extent and nature of the structural dynamics involved, and illuminating an induced fit mode of catalysis and regulation. Molecular modeling has further contributed to our understanding of the conformational changes that occur during catalysis. Here we review the data that has led to our current understanding of the structure and dynamics of this biologically and pharmaceutically important enzyme.
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PMID:Prolyl oligopeptidase structure and dynamics. 2122 26


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