Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q96FX7 (tRNA)
 26,753 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activities of alanyl- and valyl tRNA synthetases were considerably higher in rabbit muscle soleus than in muscle gastrocnemius. Repeated injections of insulin into normal rabbits as well as impairment of animals by experimental alloxan diabetes within two weeks did not alter significantly the activity of the synthetases in red and mixed muscles.
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PMID:[Valyl- and alanyl-tRNA-synthetase activity in the skeletal muscles of the rabbit in diabetes and during insulin administration]. 66 41

The activities of Val-tRNA synthetase and Ala-tRNA synthetase in the intact rabbit M. soleus are considerably higher than those in the lateral portion of the intact M. gastrocnemius. The rates of tRNA aminoacylation by the enzymes from both denervated muscles were levelled out 35 days after sciatic nerve section. Insulin injections or diabetes did not significantly influence the aminoacyl-tRNA formation catalyzed by aminoacyl-tRNA synthetases (ARS-ases) from intact muscles. Insulin substantially increased (while diabetes decreased) the activity of both enzymes in the denervated muscles. The results obtained show that the deprivation of striated muscles of trophic nervous influence results in an increase of their sensitivity to the effect of insulin on the activity of aminoacyl-tRNA-synthetases.
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PMID:[Regulation by insulin of the activity of aminoacyl-tRNA synthetases in intact and denervated rabbit muscles]. 74 12

Non-insulin-dependent (type II) diabetes mellitus (NIDDM) is characterized by hyperglycaemia and insulin resistance, and affects nearly 5% of the general population. Inherited factors are important for its development, but the genes involved are unknown. We have identified a large pedigree in which NIDDM, in combination with a sensorineural hearing loss, is maternally inherited. The maternal inheritance and the observed decrease in mitochondrial enzyme activities of the respiratory chain indicate a genetic defect in the mitochondrial DNA. An A to G transition was identified at nucleotide 3,243, a conserved position in the mitochondrial gene for tRNA(Leu)(UUR). This mutation cosegregates with the disease in this family and is absent in controls, and indicates that a point mutation in mitochondrial DNA is a pathogenetic factor for NIDDM.
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PMID:Mutation in mitochondrial tRNA(Leu)(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness. 128 50

Family studies of diabetes mellitus (DM) show that patients are more likely to have affected mothers than affected fathers. Since the inheritance of mitochondrial (mtDNA), unlike nuclear DNA, is exclusively maternal, could it be that defect(s) in mtDNA account for some cases of DM? Such defects have been associated with rare neurological syndromes, in some of which DM has been an accompanying feature. We have looked for glucose intolerance and for a previously known point mutation of mtDNA in a family, some of whose members have a multisystem disorder with DM but not neurological involvement. DNA samples were obtained from fourteen family members. The point mutation (affecting position 3243 in the tRNA leucine mitochondrial gene) was found in all three diabetic patients and post mortem tissues in the proband; it was also found in seven offspring of female patients. It was not found in the two children of the male proband. The contribution of this mutation to DM in general is not known but clinicians ought to be aware of the possibility, especially in families with multisystem disease and maternal transmission.
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PMID:Diabetes mellitus associated with a pathogenic point mutation in mitochondrial DNA. 809 44

We have recently identified a point mutation in the mitochondrially encoded tRNA(Leu(UUR)) gene which associates with a combination of type II diabetes mellitus and sensorineural hearing loss in a large pedigree. To extend this finding to other syndromes which exhibit a combination of diabetes mellitus and hearing loss we have sequenced all mitochondrial tRNA genes from two patients with the Wolfram syndrome, a rare congenital disease characterized by diabetes mellitus, deafness, diabetes insipidus and optic atrophy. In each patient, a single different mutation was identified. One is an A to G transition mutation at np 12,308 in tRNA(Leu(CUN)) gene in a region which is highly conserved between species during evolution. This mutation has been described by Lauber et al. (1) as associating with chronic progressive external ophthalmoplegia (CPEO). The other is a C to T transition mutation at np 15,904 in tRNA(Thr) gene. Both mutations are also present in the general population (frequency tRNA(Leu(CUN)) mutation 0.16, tRNA(Thr) mutation 0.015). These findings suggest that evolutionarily conserved regions in mitochondrial tRNA genes can exhibit a significant polymorphism in humans, and that the mutation at np 12,308 in the tRNA(Leu(CUN)) gene is unlikely to be associated with CPEO and Wolfram syndrome.
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PMID:Mutations in mitochondrial tRNA genes: non-linkage with syndromes of Wolfram and chronic progressive external ophthalmoplegia. 154 64

Point mutation of mitochondrial DNA has been described in the blood from a MELAS patient. The 39-year-old patient developed progressive dementia, stroke-like episodes, heart conduction defect (Lown-Ganong-Levin syndrome) and cortical blindness. CT scan revealed brain atrophy and low density areas in the bilateral occipital lobes. Laboratory tests showed hyperglycemia and lactic acidosis. Muscle biopsy showed ragged red fibers on Gomori trichrome staining. He was clinically diagnosed as having MELAS and insulin-dependent diabetes mellitus. Onset of diabetes mellitus and MELAS was almost same. Family history showed his mother's brother and sisters had also insulin-dependent diabetes mellitus. We amplified the leucine (UUR) tRNA gene from the patient's blood with polymerase chain reaction (PCR) and analysed it by restriction enzyme analysis and sequencing. Genetic analysis showed A-to-G substitution at the nucleotide position 3243 in the leucine (UUR) tRNA gene. This substitution made a new restriction site Apa I. Mutant DNA coexisted with wild type DNA (heteroplasmy). It is shown that in some types of mitochondrial encephalomyopathies, especially patients of Kearns-Sayre syndrome (KSS), diabetes mellitus is often complicated. And in KSS patients insulin receptor in normal, but insulin secretion from beta cells of pancreas is decreased. In MELAS patients, however, has diabetes mellitus been reported to be rarely complicated and relationship between MELAS and diabetes mellitus is not done. As far as we know, two cases, including ours, with genetically diagnosed MELAS have been reported to have diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[MELAS associated with diabetes mellitus and point mutation in mitochondrial DNA]. 159 Nov 3

The IIM are a heterogeneous group of systemic rheumatic diseases which share the common features of chronic muscle weakness and mononuclear cell infiltrates in muscle. A number of classification schemes have been proposed for them, but none takes into consideration the marked immunologic, clinical, and genetic heterogeneity of the various clinical groups. We compared the usefulness of myositis-specific autoantibodies (anti-aminoacyl-tRNA synthetases, anti-SRP, anti-Mi-2 and anti-MAS) to the standard clinical categories (polymyositis, dermatomyositis, overlap myositis, cancer-associated myositis, and inclusion body myositis) in predicting clinical signs and symptoms, HLA types, and prognosis in 212 adult IIM patients. Although patients with inclusion body myositis (n = 26) differed in having significantly more asymmetric and distal weakness, falling, and atrophy than other patients, there were few other significant differences among the other clinical groups. In contrast, autoantibody status defined distinct sets of patients and each patient had only 1 myositis-specific autoantibody. Patients with anti-amino-acyl-tRNA synthetase autoantibodies (n = 47), compared to those without these antibodies, had significantly more frequent arthritis, fever, interstitial lung disease, and "mechanic's hands"; HLA-DRw52; higher mean prednisone dose at survey, higher proportion of patients receiving cytotoxic drugs, and higher death rates. Those with anti-signal recognition particle antibodies (n = 7) had increased palpitations; myalgias; DR5, DRw52; severe, refractory disease; and higher death rates. Patients with anti-Mi-2 antibodies (n = 10) had increased "V-sign" and "shawl-sign" rashes, and cuticular overgrowth; DR7 and DRw53; and a good response to therapy. The 2 patients with anti-MAS antibodies were the only ones with alcoholic rhabdomyolysis preceding myositis; both had insulin-dependent diabetes mellitus, and both had HLA-B60, -C3, -DR4, and -DRw53. These findings suggest that myositis-specific autoantibody status is a more useful guide than clinical group in assessing patients with myositis, and that specific associations of immunogenetics, immune responses, and clinical manifestations occur in IIM. Thus the myositis-specific autoantibodies aid in interpreting the diverse symptoms and signs of myositis patients and in predicting their clinical course and prognosis. We propose, therefore, that an adjunct classification of the IIM, based on the myositis-specific autoantibody status, be incorporated into future studies of their epidemiology, etiology, and therapy.
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PMID:A new approach to the classification of idiopathic inflammatory myopathy: myositis-specific autoantibodies define useful homogeneous patient groups. 165 47

Is increased synthesis of proteins responsible for the hypertrophy of kidney cells in diabetes mellitus? Does the lack of insulin, and/or the effect of insulin-like growth factor I (IGFI) on renal tubule protein synthesis play a role in diabetic renal hypertrophy? To answer these questions, we determined the rates of 3H-valine incorporation into tubule proteins and the valine-tRNA specific activity, in the presence or absence of insulin and/or IGFI, in proximal tubule suspension isolated from kidneys of streptozotocin diabetic and control rats. The rate of protein synthesis increased, while the stimulatory effects of insulin and IGFI on tubule protein synthesis were reduced, early (96 hours) after induction of experimental diabetes. Thus, hypertrophy of the kidneys in experimental diabetes mellitus is associated with increases in protein synthesis, rather than with decreases in protein degradation. Factor(s) other than the lack of insulin, or the effects of IGFI, must be responsible for the high rate of protein synthesis present in the hypertrophying tubules of diabetic rats.
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PMID:Renal protein synthesis in diabetes mellitus: effects of insulin and insulin-like growth factor I. 204 44

The ability of the initiation factor eIF-2 in skeletal muscle extracts to form ternary initiation complexes ([Met-tRNA(f).eIF-2.GDP]) is decreased by either starvation or diabetes. These conditions also impair the ability of muscle extracts to dissociate [eIF-2.GDP], suggesting inhibition of the guanine nucleotide exchange reaction essential for eIF-2 recycling. We could not, however, detect any change in the phosphorylation state of the alpha subunit of eIF-2. This suggests that eIF-2 activity may be regulated in this system by a mechanism not involving its phosphorylation.
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PMID:Effect of starvation and diabetes on the activity of the eukaryotic initiation factor eIF-2 in rat skeletal muscle. 207 92

Daily minocycline-treatment of streptozotocin-induced diabetic rats not only prevented a diabetes-caused atrophy of skin collagen mass (10-mos old rats), but also normalized skin collagen mass to match that of growing (ca. 1%/d) non-diabetic controls (4- and 5-mos old rats). The causative mechanism by which minocycline-treatment normalizes skin collagen mass must, in part, be related to a general anabolic effect on growth (body weight) because the effect on skin collagen mass correlates strongly to that on body weight. Consequently, a minocycline-stimulated increase of a systemic factor (such as insulin-like growth factor) is not unlikely. The anabolic effect of minocycline-treatment of diabetic rats is also expressed as a normalized cellular ribosome mass (an index of total protein synthetic capacity) and a normalized absolute rate of collagen production. (Calculation of an absolute rate was justified by an apparent maximum saturation of the prolyl-tRNA pool(s) of skin, maximum saturation obtained by the pool-flooding approach). The normalized skin ribosome amount does not, however, explain a selective effect of minocycline-treatment on collagen production as opposed to that for non-collagen protein, this selective effect measured as relative collagen production. To explain such selectivity, the inhibition of diabetes-induced excess skin collagenase activity seems unlikely. (This inference is based on results from a preliminary study indicating that recently [less than 2 h] synthesized collagen is not degraded by the excess collagenase in skin of diabetic rats). Thus, the principal collagen fraction acted on by pathologically excess collagenase might be collagen at a later stage (greater than 2 h after synthesis) in its life cycle. (Another possibility for the selective effect of minocycline on collagen production, as yet untested, is reduced intracellular procollagen degradation.) Overall, this is the first study aimed at discerning the mechanism(s) by which minocycline-treatment enhances the rate of collagen production in tissues of a diabetic rat. For future studies, the extent to which the positive effect on growth, ribosome mass, and rate of collagen production contributes to the change of collagen mass must, along with the known minocycline-inhibition of collagenase activity, be quantified. Such quantification is a prerequisite for evaluating the chemotherapeutic efficacy of minocycline-treatment on collagen-degradative diseases.
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PMID:Minocycline-treatment of diabetic rats normalizes skin collagen production and mass: possible causative mechanisms. 237 16


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