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Query: UNIPROT:P06889 (Mol)
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The modifying potential of arecoline alkaloid was studied on hepatic drug metabolizing system enzymes, acid soluble sulfhydryl (-SH) content and microsomal lipid peroxidation. Arecoline was administered intraperitoneally to Swiss albino mice at the dose levels of 10, 20 or 40 mg/kg body wt./day for 10 or 30 days. Significant increase in the levels of glutathione S-transferase (GST), cytochrome b5 (Cyt.b5), cytochrome P-450 (Cyt.P-450) and malondialdehyde (MDA) was observed in the arecoline treated groups. Decreased -SH content was apparent by the administration of 40 mg arecoline for 10 or 30 days. The modulation in biotransformation system enzymes has wide significance in the process of neoplastic development as well as in detecting the further role of biometabolized chemicals.
Biochem Mol Biol Int 1993 Jul
PMID:Effects of arecoline on phase I and phase II drug metabolizing system enzymes, sulfhydryl content and lipid peroxidation in mouse liver. 840 32

Cytosine to thymine transition mutations at the CpG dinucleotide are the most common point mutations in cancer and genetic disease. We calculated the in vivo rate of CpG mutation in the primate germline by deriving a primordial consensus sequence for an Alu repetitive element which inserted into intron 6 of the primate p53 gene 35 to 55 million years ago. Comparison of this primordial sequence to the Alu sequence in intron 6 of present-day primates was used to determine the nature and rate of mutations which occurred during evolution. We estimate the half-life of a CpG nucleotide to be 24 to 60 million years, and the rate constant for mutation at this dinucleotide to be 1.2 x 1O(-8) to 2.9 x 1O(-8) years(-1). These results were confirmed by the analysis of a second Alu sequence in intron 10 of the p53 gene. The in vivo mutation rate is at least 1250-fold slower than the in vitro chemical rate of 5-methylcytosine deamination in double-stranded DNA, showing that current estimates of CpG mutation repair have been significantly underestimated. Furthermore, the mutability of the CpG dinucleotide has led to the depletion of this dinucleotide from the vertebrate genome, and calculations in this study suggest that current levels of the CpG dinucleotide in the primate genome are very close to a steady state equilibrium in which the rate of CpG mutation is equal to the rate of CpG formation by random mutation.
J Mol Biol 1996 May 03
PMID:The rate of CpG mutation in Alu repetitive elements within the p53 tumor suppressor gene in the primate germline. 862 22

Cytosine methylation at promoter regions and late replication timing have both been implicated in the regulation of genes subject to X chromosome inactivation. Reported here are studies of X-linked gene replication in normal male and female cells as well as in cell hybrids that contain either a normal active X, a normal inactive X, or an inactive X chromosome that has been treated with the demethylating agent, 5-azacytidine (5aC). The relationship between replication timing and transcriptional activity was examined for XIST, XPCT, PGK1, HPRT, F9, FMR1, IDS, and G6PD, and earlier replication was generally found to be associated with increased transcriptional activity. The HPRT and G6PD genes in an untreated inactive X hybrid were among the few exceptions to this correlation in that they remain inactive, yet replicate earlier than their inactive X alleles present in normal human diploid cells. This condition of earlier replication timing may contribute to the high rates of 5aC-induced reactivation for HPRT and G6PD in this hybrid relative to other inactive X hybrids. Other anomalous cases include 5aC-induced advances in replication time for genes such as XIST and F9 whose transcription was unaltered by treatment. These and other data support a model for regulation of X-inactivated genes that involves at least two levels of control: (i) large chromosomal domains are placed into a transcriptionally nonpermissive state by late replication and (ii) transcription is blocked at the local level by promoter methylation. In addition, our observations of continued XIST expression in 5aC-treated hybrids with reactivated genes indicates that such expression is not sufficient for the maintenance of X inactivation.
Hum Mol Genet 1996 Sep
PMID:Role of late replication timing in the silencing of X-linked genes. 887 76

Mitochondrial DNA of the root knot nematode Meloidogyne hapla was investigated for intraspecific diversity and divergence from other parthenogenetic root knot nematodes. A 1,900-bp fragment containing COII, tRNAHis, 16S rRNA, ND3 and Cyt b genes has been cloned and sequenced from one individual and an 1,188-bp region within this region was sequenced from four other Australian isolates. M. hapla mtDNA is more than 80% AT-rich, like other Meloidogyne spp. Nucleotide diversity within M. hapla is some 10-fold higher than across three other parthenogenetic species of root-knot nematode (M. arenaria, M. javanica, and M. incognita), implying an earlier origin for M. hapla. Nucleotide divergence between M. hapla and its congener M. javanica is as great as that between Ascaris suum and Caenorhabditis elegans, members of different nematode subclasses, while amino acid sequence difference between Meloidogyne is more than twice as great. This is interpreted as an AT-bias-induced acceleration of the amino acid substitution rate, over and above saturation of nucleotide divergence in the strongly AT-biased DNA, on three lines of evidence: (1) in conserved blocks in 16S rDNA congeneric Meloidogyne have no more differences than between A. suum and C. elegans; (2) the Meloidogyne lineage has more amino acid changes relative to the Ascaris/Caenorhabditis lineage with respect to four of five outgroups, the exceptional outgroup being the only species (Apis) as AT-rich as Meloidogyne; and (3) between the two Meloidogyne there are more first and second but fewer third codon position changes than between the other nematode species. M. hapla is also found to contain a 102-bp tandem repeat of at least 40 copies; a size, arrangement, and position the same as in M. javanica, but sequence comparisons did not demonstrate homology between the two repeats.
Mol Biol Evol 1997 Jan
PMID:Evolution of the AT-rich mitochondrial DNA of the root knot nematode, Meloidogyne hapla. 900 Jul 52

Calmidazolium potently stimulated steroidogenesis in a mouse adrenocortical Y1 cell line, in a Ca(2+)-independent manner, an effect similar to that reported by Choi and Cooke [1] for rat primary adrenocortical and Leydig cells. Calmidazolium analogues, econazole and miconazole, were shown to inhibit both this calmidazolium-stimulated rate and the endogenous rate of steroidogenesis. In determining the mechanism by which imidazole compounds affect steroidogenesis, they were found not to act directly on the mitochondrial Cyt P-450scc enzyme, making it likely that they act instead on the intramitochondrial transport of cholesterol. Using competition binding studies, calmidazolium, econazole and miconazole were subsequently identified as novel ligands for the peripheral-type benzodiazepine receptor (PBR). Econazole and miconazole were found to inhibit stimulation by PK 11195 (a specific PBR ligand) of steroidogenesis, whereas treatment of the cells with calmidazolium and PK 11195 at the same time resulted in an additive stimulatory effect on steroidogenesis. These results suggest that the effects of these substituted imidazoles on steroidogenesis in Y1 cells is not mediated through their interaction with the PBR.
J Steroid Biochem Mol Biol 1997 Feb
PMID:Calmidazolium and other imidazole compounds affect steroidogenesis in Y1 cells: lack of involvement of the peripheral-type benzodiazepine receptor. 919 76

The nucleotide sequences of two segments of 6,737 ntp and 258 nto of the 18.4-kb circular mitochondrial (mt) DNA molecule of the soft coral Sarcophyton glaucum (phylum Cnidaria, class Anthozoa, subclass Octocorallia, order Alcyonacea) have been determined. The larger segment contains the 3' 191 ntp of the gene for subunit 1 of the respiratory chain NADH dehydrogenase (ND1), complete genes for cytochrome b (Cyt b), ND6, ND3, ND4L, and a bacterial MutS homologue (MSH), and the 5' terminal 1,124 ntp of the gene for the large subunit rRNA (1-rRNA). These genes are arranged in the order given and all are transcribed from the same strand of the molecule. The smaller segment contains the 3' terminal 134 ntp of the ND4 gene and a complete tRNA(f-Met) gene, and these genes are transcribed in opposite directions. As in the hexacorallian anthozoan, Metridium senile, the mt-genetic code of S. glaucum is near standard: that is, in contrast to the situation in mt-genetic codes of other invertebrate phyla, AGA and AGG specify arginine, and ATA specifies isoleucine. However, as appears to be universal for metazoan mt-genetic codes, TGA specifies tryptophan rather than termination. Also, as in M. senile the mt-tRNA(f-Met) gene has primary and secondary structural features resembling those of Escherichia coli initiator tRNA, including standard dihydrouridine and T psi C loop sequences, and a mismatched nucleotide pair at the top of the amino-acyl stem. The presence of a mutS gene homologue, which has not been reported to occur in any other known mtDNA, suggests that there is mismatch repair activity in S. glaucum mitochondria. In support of this, phylogenetic analysis of MutS family protein sequences indicates that the S. glaucum mtMSH protein is more closely related to the nuclear DNA-encoded mitochondrial mismatch repair protein (MSH1) of the yeast Saccharomyces cerevisiae than to eukaryotic homologues involved in nuclear function, or to bacterial homologues. Regarding the possible origin of the S. glaucum mtMSH gene, the phylogenetic analysis results, together with comparative base composition considerations, and the absence of an MSH gene in any other known mtDNA best support the hypothesis that S. glaucum mtDNA acquired the mtMSH gene from nuclear DNA early in the evolution of octocorals. The presence of mismatch repair activity in S. glaucum mitochondria might be expected to influence the rate of evolution of this organism's mtDNA.
J Mol Evol 1998 Apr
PMID:Mitochondrial DNA of the coral Sarcophyton glaucum contains a gene for a homologue of bacterial MutS: a possible case of gene transfer from the nucleus to the mitochondrion. 954 36

The crystal proteins of Bacillus thuringiensis have been extensively studied because of their pesticidal properties and their high natural levels of production. The increasingly rapid characterization of new crystal protein genes, triggered by an effort to discover proteins with new pesticidal properties, has resulted in a variety of sequences and activities that no longer fit the original nomenclature system proposed in 1989. Bacillus thuringiensis pesticidal crystal protein (Cry and Cyt) nomenclature was initially based on insecticidal activity for the primary ranking criterion. Many exceptions to this systematic arrangement have become apparent, however, making the nomenclature system inconsistent. Additionally, the original nomenclature, with four activity-based primary ranks for 13 genes, did not anticipate the current 73 holotype sequences that form many more than the original four subgroups. A new nomenclature, based on hierarchical clustering using amino acid sequence identity, is proposed. Roman numerals have been exchanged for Arabic numerals in the primary rank (e.g., Cry1Aa) to better accommodate the large number of expected new sequences. In this proposal, 133 crystal proteins comprising 24 primary ranks are systematically arranged.
Microbiol Mol Biol Rev 1998 Sep
PMID:Revision of the nomenclature for the Bacillus thuringiensis pesticidal crystal proteins. 972 10

Rates of sequence evolution were estimated for the cytochrome b (cyt b) and NADH dehydrogenase sub-unit 2 (ND2) genes using a phylogeny of the dabbling ducks (Tribe: Anatini) and outgroups. This speciose group was densely sampled, reducing the impact of undetected homoplasy on rate comparisons. Phylogenies based on sequences of the two gene regions and various weighting schemes differed, but most of the differences involved weakly supported nodes. In addition, partition homogeneity tests show that these differences were not due to statistically significant conflict between the data sets. Cyt b and ND2 also showed similar rates and types of both nucleotide and amino acid substitutions. For both genes, substitutions between isoleucine and valine and between alanine and threonine were most common; both of these substitution types are the result of A-G transitions at first positions of codons. Rates of sequence evolution varied substantially and significantly among nucleotide positions, and even within a given codon position (first, second, or third), rates were significantly heterogeneous among sites. Within Anatini, cyt b and ND2 show similar levels of variation and homoplasy, and are equally useful for reconstructing the species level phylogeny of this group.
Mol Phylogenet Evol 1998 Aug
PMID:Comparing molecular evolution in two mitochondrial protein coding genes (cytochrome b and ND2) in the dabbling ducks (Tribe: Anatini). 975 19

We have carried out a physicochemical and computational analysis on the stability of the intercalated structures formed by cytosine-rich DNA strands. In the computational study, the electrostatic energy components have been calculated using a Poisson-Boltzmann model, and the non-polar energy components have been computed with a van der Waals function and/or a term dependent on the solvent-accessible surface area of the molecules. The results have been compared with those obtained for Watson-Crick duplexes and with thermodynamic data derived from UV experiments. We have found that intercalated DNA is mainly stabilized by very favorable electrostatic interactions between hydrogen-bonded protonated and neutral cytosines, and by non-polar forces including the hydrophobic effect and enhanced van der Waals contacts. Cytosine protonation electrostatically promotes the association of DNA strands into a tetrameric structure. The electrostatic interactions between stacked C.C+ pairs are strongly attenuated by the reaction field of the solvent, and are modulated by a complex interplay of geometric and protonation factors. The forces stabilizing intercalated DNA must offset an entropic penalty due to the uptake of protons for cytosine protonation, at neutral pH, and also the electrostatic contribution to the solvation free energy. The latter energy component is less favorable for protonated DNA due to the partial neutralization of the negative charge of the molecule, and probably affects other protonated DNA and RNA structures such as C+-containing triplexes.
J Mol Biol 1999 Jan 22
PMID:The folding of centromeric DNA strands into intercalated structures: a physicochemical and computational study. 988 66

Cardiac hypertrophic growth secondary to hemodynamic pressure overload causes changes in energy requirements that may involve the transcriptional upregulation of oxidative phosphorylation genes. Therefore, two representative nuclear-encoded genes, the mitochondrial F1-ATP synthase beta-subunit (beta-subunit) and cytochrome c (cyt c), were examined in a feline chronic pulmonary artery banded right ventricular pressure-overload model. In the hypertrophying right ventricle, beta-subunit and cyt c mRNA levels increased after two and seven days, during the peak growth response. To examine cardiac transcriptional regulation, neonatal rat cardiac myocytes (cardiocytes) were transiently transfected with beta-subunit promoter constructs ranging from -1519 nucleotides (nt) upstream of transcription initiation as well as cyt c promoter constructs ranging from -726 nt. A full-length p1519beta-subunit/Luc construct was alpha-adrenergically inducible by 275% (+/-30%) with this activation being mapped to an enhancer region between -1519 to -1480 nt. Smaller constructs containing more proximal promoter elements were not inducible. Additionally, the full-length and enhancer deleted beta-subunit constructs were also inducible in electrically stimulated cardiocytes, suggesting a different mechanism of activation. Cyt c constructs containing known constitutive elements from -191 to -167 nt and -139 to -84 nt were responsible for the majority of the reporter activity of the full-length promoter but were not inducible in the presence of phenylephrine. Hence, we show that promoter regions containing elements common in other metabolism-related gene families are active in neonatal rat cardiocytes. Once more, we have identified a beta-subunit genomic region responsive to alpha-adrenergic and electrical stimulation.
J Mol Cell Cardiol 1999 Jan
PMID:F1-ATP synthase beta-subunit and cytochrome c transcriptional regulation in right ventricular hemodynamic overload and hypertrophically stimulated cardiocytes. 1007 25


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