Literature Search Results for Gene PLG

PLG
1
Peptides 2003 Jan 24: 137-46
PMID12576095
TitlePLG regulates hnRNP-L expression in the rat striatum and pre-frontal cortex: identification by ddPCR.
AbstractCentral dopaminergic systems are implicated in schizophrenia and Parkinson's disease, and are known to be modulated by the endogenous tripeptide Pro-Leu-Gly-NH(2) (PLG or MIF-1, melanocyte-stimulating hormone release inhibiting factor-1). Differential display polymerase chain reaction (ddPCR) was utilized to identify genes that are regulated by protracted PLG treatment (20 mg/kg, i.p. for 28 days) in male Sprague-Dawley rats. A total of 2400 genes were screened and 3 down-regulated bands were identified in the PLG-treated samples. Sequencing analysis revealed a total of six unique cDNA species. One fragment possessed a high degree of homology with Mus musculus hnRNP-L (protein L) mRNA (GenBank #AB009392) (termed PRG1: PLG regulated gene 1). Elongation of the PRG1 cDNA, by RACE-PCR, provided an 835 bp sequence with 95% homology to AB009392 over a 743 bp span. Open reading frame analysis provided a putative amino acid sequence consistent with the identity of PRG1 as rat hnRNP-L. Northern hybridization experiments with PRG1 revealed a 2.3 kb mRNA species that was decreased by 65% in the PLG-treated tissue. Western blot analysis revealed significantly decreased hnRNP-L levels in the striatum and pre-frontal cortex (but not the nucleus accumbens) by 71 and 61%, respectively of PLG-treated animals. The identification of altered expression of hnRNP-L following PLG treatment provides insight into the long-term effects of PLG and may provide insight into its molecular mechanism of action.
SCZ Keywordsschizophrenia,schizophrenic
2
Theochem 2010 Mar 944: 76-82
PMID20401321
TitleEvaluation of Density Functionals, SCC-DFTB, Neglect of Diatomic Differential Overlap (NDDO) Models and Molecular Mechanics Methods for Prolyl-Leucyl-Glycinamide (PLG) and Structural Derivatives.
AbstractProlyl-leucyl-glycinamide (PLG) is a unique endogenous peptide that modulates dopamine receptor subtypes of the D(2) receptor family within the CNS. We seek to elucidate the structural basis and molecular mechanism by which PLG and its analogues modulate dopamine receptors, toward the development of new therapeutics to treat Parkinson's disease, tardive dyskinesia and schizophrenia. As a first step toward establishing a validated protocol for accurate computational modeling of PLG and associated peptidomimetic analogues, we evaluated the accuracy of density functional theory (DFT), wavefunction theory (WFT), and molecular mechanics (MM) calculations for PLG and for a library of structurally related small molecules. We first tested twelve local and nonlocal density functionals, Hartree-Fock (HF) theory, four "semiempirical" methods of the neglect of diatomic differential overlap (NDDO) type, and one self-consistent-charge nonorthogonal tight-binding (SCC-DFTB) method as implemented in two software suites, against coupled-cluster benchmark geometries for 4-methylthiazolidine, a small molecule that comprises key structural features present in our PLG analogue library. DFT and HF calculations were done with the MG3S augmented polarized triple-zeta basis set. We find that for 4-methylthiazolidine bond distances, DFT significantly outperforms NDDO, and both SCC-DFTB versions we evaluated perform worse than HF theory and are less accurate than 83% of the density functionals tested. The top five functionals for 4-methylthiazolidine were M05-2X, mPW1PW, B97-2, M06-2X, and PBEh, with mean unsigned errors (MUEs) in bond length of 0.0017, 0.0020, 0.0023, 0.0025 and 0.0027 Å, respectively. The widely used B3LYP functional ranked 11(th) out of twelve functionals evaluated, slightly below SCC-DFTB, and is significantly less accurate for 4-methylthiazolidine bond distances (MUE = 0.0095 Å) than the best local functional (M06-L, MUE = 0.0030 Å), which is far less computationally costly. Based on that initial analysis, we obtained new M05-2X benchmark geometric parameters for PLG and a library of eleven peptidomimetic derivatives, which we in turn used to examine the accuracy of thirty-four popular molecular mechanics (MM) force fields, four NDDO approaches, and SCC-DFTB for the full compound structures. Here, we found that ?70% of the MM force fields tested superior to the best semiempirical and SCC-DFTB codings. Moreover, AMBER-type force fields proved most accurate among MM methods for this class of small-molecule peptidomimetics; the AMBER-type methods comprised eight out of the top ten molecular mechanics options we tested.
SCZ Keywordsschizophrenia,schizophrenic
3
Schizophr. Res. 2011 Jan 125: 88-92
PMID21036015
TitlePAOPA, a potent analogue of Pro-Leu-glycinamide and allosteric modulator of the dopamine D2 receptor, prevents NMDA receptor antagonist (MK-801)-induced deficits in social interaction in the rat: implications for the treatment of negative symptoms in schizophrenia.
AbstractThe aim of this study was to investigate whether a potent analogue of the endogenous brain peptide l-prolyl-l-leucyl-glycinamide (PLG), (3(R)-[(2(S)-pyrrolidinylcarbonyl)amino]-2-oxo-1-pyrrolidineacetamide (PAOPA), can prevent the induction of social withdrawal caused by sub-chronic treatment with the non-competitive NMDA (N-methyl-l-aspartate) receptor antagonist, MK-801. Results indicate that MK-801 (0.5 mg/kg) significantly decreased social interaction following sub-chronic treatment (7 days). Treatment with PAOPA (1 mg/kg) blocked the effects of MK-801, and increased the amount of time spent in social interaction in comparison to control animals. These results provide evidence for the development of peptidomimetic compounds for the treatment of social withdrawal and related negative symptoms associated with schizophrenia.
SCZ Keywordsschizophrenia,schizophrenic


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