Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitochondrial adenosine triphosphate (ATP) generation plays a major role in insulin secretion in pancreatic islet beta cells. The relationship between age and nutritional status of the islet and mitochondrial gene messenger RNA (mRNA) expression was investigated. Three animal groups were studied: infant (12-day-old) rats fed either mother's milk or a high carbohydrate (HC) diet; young (2 to 4-month-old) rats; and old (12 to 14-month-old) rats. The expression of mitochondrial cytochrome oxidase (CYO) (subunits I, II, and III), beta-nicotinamide adenine dinucleotide, reduced form dehydrogenase subunit 4 (NADH-DH4), and ATP synthase (subunit 6) (ATP-SYN6) mRNAs was characterized by semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR). The mitochondrial gene mRNAs were identified in each of the groups of rat islets and in RINm5F cells. CYO-II mRNA expression in young and old rat pancreatic islets was 12.7- and 8.2-fold higher, respectively, compared with the level in infant rat islets. The expression of NADH-DH4 and ATP-SYN6 mRNAs was 47% and 40% lower, respectively, in young rat islets compared with the level in infant rat islets. CYO-I, CYO-III, and cytoplasmic glyceraldehyde-3-phosphate dehydrogenase (GPDH) mRNA expression did not differ between experimental groups. Artificial rearing of infant rat pups on a HC diet for 8 days lead to a 3.3-fold increase in islet CYO-II mRNA expression compared with mother-fed pups. However, glucose (11 mmol/L) stimulation of cultured isolated islets from young and old rats for 4 days failed to affect the expression level of mitochondrial gene mRNAs. Thus, aging affected the differential expression of CYO-II, NADH-DH4, and ATP-SYN6 mRNAs in rat islets. CYO-II mRNA expression was modulated only in infant rat islets after in vivo administration of carbohydrate.
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PMID:Mitochondrial-encoded gene regulation in rat pancreatic islets. 1122 30

Nucleoside reverse-transcriptase inhibitor (NRTI) therapy for human immunodeficiency virus (HIV) infection has been associated with mitochondrial DNA (mtDNA) polymerase-gamma inhibition and subsequent mtDNA depletion. Effects on mtDNA mutation, although suggested by critical involvement of polymerase-gamma in DNA-repair reactions, are unknown. In the present study, we assessed the nature and frequency of mitochondrial genome sequence differences in peripheral-blood samples taken prior to NRTI therapy and after 6-77 mo of treatment in 16 NRTI-treated patients. Samples from 10 HIV-infected, treatment-naive control individuals were taken at similar time intervals. Single-stranded conformation polymorphism (SSCP) and DNA-sequencing analysis techniques were used to detect mitochondrial genome sequence variants between paired longitudinal samples, and heteroplasmic populations were quantified after cloning and repeat SSCP/sequencing. Of 16 individuals treated with NRTIs, 5 exhibited altered SSCP profiles associated with the development of novel heteroplasmic DNA sequence changes, whereas no SSCP pattern change within these regions was observed in the control individuals. Heteroplasmic sequence changes were distributed across four regions of the genome: the noncoding region to 12S ribosomal RNA, reduced-nicotinamide-adenine-dinucleotide dehydrogenase 1, and cytochrome oxidase subunits I and III. Of the total of 26 patients who were examined in the present study, 4 of 5 patients with detectable mtDNA sequence changes since commencement of therapy developed evidence of peripheral fat wasting (lipoatrophy) between sample intervals (P=.031). One patient, without detectable sequence changes on NRTI therapy, also developed lipoatrophy. Levels of mtDNA copies/cell in blood samples were determined by quantitative PCR for 11 of the 16 NRTI-exposed patients; 7 of these 11 patients showed reduced levels of mtDNA in blood after therapy, including all 3 patients tested with evidence of mtDNA sequence changes on therapy. These data indicate that NRTI therapy provides conditions permissive for the development of peripheral-blood mtDNA mutations in vivo.
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PMID:Accumulation of mitochondrial DNA mutations in human immunodeficiency virus-infected patients treated with nucleoside-analogue reverse-transcriptase inhibitors. 1258 93

To study the link between energy metabolism and secondary metabolism/morphological development in Streptomyces, knockout mutants were generated with regard to the subunits of the cytochrome oxidase supercomplex (CcO) in Streptomyces coelicolor A3(2). All mutants exhibited an identical phenotype: viable but defective in antibiotic production and cell differentiation when grown in both complex and minimal media. The growth yield of the CcO mutant was about half of that of the WT strain on glucose medium while both strains grew similarly on maltose medium. Intracellular ATP measurement demonstrated that the CcO mutant exhibited high intracellular ATP level. A similar elevation of intracellular ATP level was observed with regard to the WT strain cultured in the presence of BCDA, a copper-chelating agent. Reverse transcriptase PCR analysis demonstrated that the transcription of ATP synthase operon is upregulated in the CcO mutant. Addition of carbonylcyanide m-chlorophenylhydrazone, an inhibitor of ATP synthesis, promoted antibiotic production and aerial mycelia formation in the CcO mutant and BCDA-treated WT cells. We hypothesize that the deficiency of CcO causes accumulation of intracellular ATP, and that the high ATP level inhibits the onset of development in S. coelicolor.
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PMID:Developmental defect of cytochrome oxidase mutants of Streptomyces coelicolor A3(2). 2738 68