Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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When present in high copy number plasmids, the nuclear genes MRS3 and MRS4 from Saccharomyces cerevisiae can suppress the mitochondrial RNA splicing defects of several mit- intron mutations. Both genes code for closely related proteins of about Mr 32,000; they are 73% identical. Sequence comparisons indicate that MRS3 and MRS4 may be related to the family of mitochondrial carrier proteins. Support for this notion comes from a structural analysis of these proteins. Like the ADP/ATP carrier protein (AAC), the mitochondrial phosphate carrier protein (PiC) and the uncoupling protein (UCP), the two MRS proteins have a tripartite structure; each of the three repeats consists of two hydrophobic domains that are flanked by specific amino acid residues. The spacing of these specific residues is identical in all domains of all proteins of the family, whereas spacing between the hydrophobic domains is variable. Like the AAC protein, the MRS3 and MRS4 proteins are imported into mitochondria in vitro and without proteolytic cleavage of a presequence and they are located in the inner mitochondrial membrane. In vivo studies support this mitochondrial localization of the MRS proteins. Overexpression of the MRS3 and MRS4 proteins causes a temperature-dependent petite phenotype; this is consistent with a mitochondrial function of these proteins. Disruption of these genes affected neither mitochondrial functions nor cellular viability. Their products thus have no essential function for mitochondrial biogenesis or for whole yeast cells that could not be taken over by other gene products. The findings are discussed in relation to possible functions of the MRS proteins in mitochondrial solute translocation and RNA splicing.
J Mol Biol 1991 Jan 05
PMID:MRS3 and MRS4, two suppressors of mtRNA splicing defects in yeast, are new members of the mitochondrial carrier family. 170 36

11 recombinant bacteriophages from the genomic library of Djungarian hamster genome, that carry MMTV-related sequences (MRS-Ps), have been cloned with the murine mammary cancer virus (MMTV) as a hybridization probe. The sequences are repeated 50 times in the genome. MRS-Ps contain the tracts of homology with the long end repeat MMTV, the genes pol and, possibly, env, but not with the gag gene. Sequencing of the 0,87 kb restrict, common to all EcoRI-BamHI clones, and the analysis of the sequence have demonstrated the high level of homology with the pol gene of MMTV and its origination from the somewhat functioning gene.
Mol Gen Mikrobiol Virusol 1989 Oct
PMID:[Cloning and analysis of the primary structure of an element, related to the murine mammary cancer virus, from the genome of the Djungarian hamster]. 255 24

Mutator stocks of maize exhibit a high mutation rate correlated with the activity of a family of transposable elements. Mu1 and, to a lesser extent, the closely related Mu1.7 elements are responsible for most mutator-induced mutations that have been characterized. These elements are found in 10-60 copies in mutator stocks, and zero to a few intact elements exist in nonmutator maize stocks. Additionally, the component parts of Mu elements exist separately in the maize genome. The Mu terminal inverted repeats are found in multiple copies in all maize lines and related Zea species tested, and Mu internal sequences exist unassociated with Mu termini. In the present paper, we describe the structure and genomic distribution of one Mu-homologous sequence termed MRS-A (for Mu-related sequence). DNA sequencing shows that MRS-A is closely related to the internal region of Mu1 and Mu1.7 elements. However, it has no Mu termini and does not have the structure of a transposable element. This sequence is present in one or two copies in all maize lines and is highly conserved in the genus Zea. A similar sequence exists in a species within the genus most closely related to Zea, Tripsacum dactyloides, although the T. dactyloides genome does not contain any Mu termini or intact Mu elements. Furthermore, an RNA transcript homologous to MRS-A and its flanking DNA is found in both mutator and nonmutator maize plants. These results suggest that MRS-A represents a stable, functional region of the maize genome, and we speculate that a similar sequence was encompassed by Mu termini to generate a Mu transposable element.
Mol Biol Evol 1988 Sep
PMID:Characterization of a highly conserved sequence related to mutator transposable elements in maize. 284 75

N-methyl-D-aspartate (NMDA) receptor antagonists have been demonstrated widely to be neuroprotective in cerebral ischemia, hypoxia, and traumatic brain injury. However, although noncompetitive NMDA antagonists have typically proven efficacious under all of these conditions, competitive antagonists have not been shown to be beneficial following moderate traumatic brain injury. The present study has used phosphorus magnetic resonance spectroscopy ([31P]MRS) to examine the effects of the competitive antagonist cis-4-(phosphonomethyl) piperidine-2-carboxylic acid (CGS-19755) and the noncompetitive antagonist dextromethorphan on biochemical outcome following fluid percussion-induced traumatic brain injury in rats. Five minutes prior to induction of moderate (2.8 +/- 0.2 atm) fluid percussion brain injury, animals received either CGS-19755 (10 mg/kg iv), dextromethorphan (10 mg/kg iv), or equal volume saline vehicle. [31P]MRS spectra were then acquired for 4 h post-trauma and intracellular pH, free magnesium concentration, cytosolic phosphorylation potential, and oxidative capacity determined. Both CGS-19755-treated animals and saline treated controls demonstrated significant and sustained declines in intracellular free magnesium concentration and bioenergetic status following trauma. In contrast, administration of dextromethorphan significantly attenuated free magnesium decline and improved bioenergetic state during the post-traumatic monitoring period. These results suggest that the neuroprotective actions of NMDA antagonists following traumatic brain injury are associated with attenuation of free magnesium decline and that such actions seem to be preferentially mediated by noncompetitive blockers.
Mol Chem Neuropathol
PMID:Efficacy of competitive vs noncompetitive blockade of the NMDA channel following traumatic brain injury. 763 18

Phosphorus magnetic resonance spectroscopy (31P-MRS) has emerged as a noninvasive reliable tool for in vivo study of human tissue bioenergetics. It detects and quantifies some phosphorylated compounds present in millimolar concentration inside the cell, including ATP, phosphocreatine (PCr) and inorganic phosphate (Pi). By 31P-MRS we studied brain and skeletal muscle energy metabolism of three patients with retinitis pigmentosa before and after oral coenzyme Q10 (CoQ10) (100 mg/day). Before treatment we found a low PCr content in the brains of all patients, accompanied by a high [Pi] and high [ADP]. In two of three patients CoQ10 treatment resulted in a larger brain energy reserve mainly shown by an increased [PCr]. Abnormal muscle mitochondrial function was found only in one patient as shown by a reduced rate of PCr resynthesis after exercise. In this patient CoQ10 treatment resulted in an increased rate of PCr resynthesis. Our observations indicate that CoQ10 can improve mitochondrial functionality in the brain and skeletal muscle of patients with retinitis pigmentosa.
Mol Aspects Med 1994
PMID:The use of phosphorus magnetic resonance spectroscopy to study in vivo the effect of coenzyme Q10 treatment in retinitis pigmentosa. 775 34

The complete nucleotide sequence of the dwarf hamster endogenous retrovirus (MRS-Ps) related to the mouse mammary tumor virus is presented. MRS-Ps has a typical retroviral structure, it is 6980 bp long with LTRs of ca. 880 base pairs at both ends. LTRs carry the usual signals for transcription control. MRS-Ps genes had formerly coded for viral proteins (protease, revertase, and envelope proteins) but have been spoiled by numerous point mutations. Evolutionary relationships with other retroviruses are discussed on the basis of computer analysis of the MRS-Ps sequence.
Mol Biol (Mosk)
PMID:[Analysis of the sequence of the endogenous Djungarian hamster provirus (MRS-Ps) related to the murine mammary cancer virus]. 799 Aug 18

Energy transduction in mitochondria requires the transport of many specific metabolites across the inner membrane of this eukaryotic organelle. We have screened the protein sequence database for proteins homologous to the mitochondrial ATP/ADP exchange carrier, and the homologous proteins found were similarly screened to ensure that all currently sequenced members of the mitochondrial carrier family (MCF) had been identified. Thirty-seven proteins were identified, 28 of which were less than 90% identical to any other sequenced member of the MCF, and the latter proteins fell into 10 clusters or subfamilies as follows: (1) ATP/ADP exchangers of mammals, plants, algae, yeast, and fungi (11 members); (2) a bovine oxoglutarate/malate exchanger (one member); (3) mammalian uncoupling carriers (five members); (4) yeast and mammalian phosphate carriers (three members); (5) MRS proteins that suppress mitochondrial splicing defects in Saccharomyces cerevisiae (two members); (6) a putative peroxysomal carrier of Candida boidinii; (7) a putative solute carrier from the protozoan, Oxytricha fallax; (8) a putative solute carrier from S. cerevisiae; (9) a putative solute carrier from Zea mays, and (10) two putative solute carriers from the mammalian thyroid gland. The specificities of proteins in clusters 5 to 10 are not known. A multiple alignment and an evolutionary tree of the 28 selected members of the MCF were constructed, thus defining the conserved residues and the phylogenetic relationships of the proteins. Hydropathy plots of the homologous regions were determined and averaged, and the average hydropathy plots were evaluated for sequence similarity. These analyses revealed that the six transmembrane spanners exhibited varying degrees of sequence conservation and hydrophilicity. These spanners, and immediately adjacent hydrophilic loop regions, were more highly conserved than other regions of these proteins. All members of the MCF appear to consist of a tripartite structure with each of the three repeated segments being about 100 residues in length. Each repeat contains two transmembrane spanners, the first being more hydrophobic with conserved glycyl and prolyl residues, the second, preceded by a highly conserved glycyl residue, being more hydrophilic with largely conserved hydrophilic residues in certain positions. Five of the six spanners are followed by the largely conserved sequence (D/E)-Hy (K/R)[- = any residue; Hy = a hydrophobic residue]. Based on both intracluster and intercluster statistical comparisons, repeats 1, 2, and 3 are homologous, but repeats 1 are more similar to each other than they are to repeats 2 or 3 or repeats 2 or 3 are to each other.(ABSTRACT TRUNCATED AT 400 WORDS)
Crit Rev Biochem Mol Biol 1993
PMID:The mitochondrial carrier family of transport proteins: structural, functional, and evolutionary relationships. 832 39

4.1 CURRENT STATUS. While an extensive clinical literature of MRS of muscle, brain, heart and liver has been achieved, the MRS technique is not considered essential for routine diagnosis because it is inherently insensitive and metabolic changes tend to be small. However, MRS techniques have proven to be of considerable value for prognosis in some circumstances, notably for predicting outcome following hypoxic-ischaemic injury in the newborn and also in predicting graft viability following organ transplantation. The chemical specificity of MRS has been illustrated, and exploiting the non-invasive nature of the technique, metabolic fingerprinting of pathophysiological processes throughout the natural history of a wide variety of diseases is now being accomplished. Particularly exciting are the applications of 13C MRS for measuring hepatic and muscle glycogen levels, for example in diabetics, and the use of hepatic 31P MRS for assessing liver function in cirrhosis. Other areas of excitement are the applications of 1H MRS in assessing neuronal function in epilepsy and stroke, and for measuring the evolution of lactate in stroke and hypoxic-ischaemic encephalopathy. Emphasis on technique development continues, and applications still tend to be technology-led. The availability of routine clinical MRI systems with spectroscopy capabilities has given MRS studies wider applicability. The recent improvements in spatial resolution have been impressive and the technique is slowly becoming more quantitative. 4.2. FUTURE PERSPECTIVES. Given the flexibility of clinical magnetic resonance techniques, particularly magnetic resonance imaging, it is likely that MRI will be the diagnostic tool of choice in a wider range of diseases, such as multiple sclerosis, stroke, neurodegenerative conditions, sports injuries and in staging malignancies. Since proton magnetic resonance spectroscopy packages have become a routine addition to many MRI systems, it is feasible to select the MRI sequences of most value in highlighting anatomical and pathological abnormalities and to incorporate specifically selected MRS sequences to emphasize biochemical differences. Improvements in technical methodologies are central to further developments. For example, use of internal coils, such as implantable or endoscopic coils, will enable small regions of tissue to be studied in considerable detail, which may otherwise be inaccessible to measurement. Chemical MRS studies have benefited from the use of higher magnetic fields, and the same may be expected for clinical MRS studies. Whole-body magnets up to 4 T have been used in a few centres, and certainly 3 T systems are becoming more widely available with the recent tremendous interest in functional imaging. Certainly, better control of artefacts can be expected; for example, improved definition of spectral changes due to voluntary or involuntary movements. Wider use of proton decoupling methods will improve the specificity of the spectra, by allowing definitive assignments of overlapping resonances, as well as the sensitivity. Comparing PET and MRS studies, it is becoming increasingly obvious that both will be required in parallel to explore parameters of brain metabolism and function. The ability to measure 13C MR signals in the brain has been demonstrated, which allows measurements of glutamate and glucose turnover. MRS measurements have the advantage of not requiring a radioactive isotope, as well as being insensitive to activity-related changes in regional cerebral blood flow. Also the study of cerebral glucose metabolism by MRS is very promising, allowing a resolution and sensitivity comparable to PET. A combination of MRS and PET studies will allow the pathogenesis of neuropsychiatric disorders to be better understood. (ABSTRACT TRUNCATED)
Prog Biophys Mol Biol 1996
PMID:Development and applications of in vivo clinical magnetic resonance spectroscopy. 902 41

High resolution 1H MRS studies report increased mobile neutral lipid (MNL) signals in transformed and malignant as well as in some in vitro cultured embryonic cells. Nature, subcellular localization and biological function of MNL are still under debate. This work was aimed at assessing alterations induced in MNL signals of NIH-3T3 mouse embryo fibroblasts by transformation with human HJ-ras oncogene. Lower MRS-visible MNL levels were unexpectedly detected in ras-transformed, in vivo tumorigenic fibroblasts, with respect to their untransformed and non-tumorigenic parental cells. MRS, gas chromatography and chemical analysis on cells and their lipid extracts indicated that these spectral differences could hardly be attributed to different triacylglycerol, free fatty acids and total cholesterol levels or to changes in the fatty acyl degree of unsaturation and average chain length. Additional, possibly more relevant mechanisms of regulation of MNL mobility may implicate the extensive morphogenetic changes and reorganization of cytoskeleton components (notably actin) associated with ras-transformation.
Cell Mol Biol (Noisy-le-grand) 1997 Jul
PMID:Lower levels of 1H MRS-visible mobile lipids in H-ras transformed tumorigenic fibroblasts with respect to their untransformed parental cells. 929 91

With phosphorus magnetic resonance spectroscopy (31P-MRS) we studied in vivo the effect of six-month coenzyme Q10 treatment on the efficiency of brain and skeletal muscle mitochondrial respiration in six patients with different mitochondrial cytopathies. Before CoQ we found a low phosphocreatine content (average of 25% decrease from controls) in the occipital lobes of all patients. Calculated [ADP] and the relative rate of ATP synthesis were high (as an average, 57% and 16% above control group respectively), whereas the cytosolic phosphorylation potential was low (as an average, 60% of control value). 31P-MRS also revealed an average of 29% reduction of the mitochondrial function in the skeletal muscle of patients compared with controls. After a six-month treatment with 150 mg CoQ10/day all brain variables were remarkably improved in all patients, returning within the control range in all cases. Treatment with CoQ also improved the muscle mitochondrial functionality enough to reduce the average deficit to 56% of the control group. These in vivo findings show the beneficial effect of CoQ in patients with mitochondrial cytopathies, and are consistent with the view that increased CoQ concentration in the mitochondrial membrane increases the efficiency of oxidative phosphorylation independently of enzyme deficit.
Cell Mol Biol (Noisy-le-grand) 1997 Jul
PMID:Coenzyme Q10 improves mitochondrial respiration in patients with mitochondrial cytopathies. An in vivo study on brain and skeletal muscle by phosphorous magnetic resonance spectroscopy. 929 96


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