Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.3.5.1 (succinate dehydrogenase)
 8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using in situ hybridization, we studied muscle biopsy specimens from 4 patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Three of the 4 patients with MELAS had a mutation at position 3243 of mitochondrial DNA (mtDNA) in the transfer RNALeu(UUR) gene, and the other patient had a mutation at position 3271 in the same transfer RNALeu(UUR) gene. Quantitative analysis using Southern blot hybridization and polymerase chain reaction showed 80 to 90% mutant mtDNA in muscle. In situ hybridization analysis showed that total mtDNAs (both normal and mutant) were extremely increased in blood vessels with high succinate dehydrogenase activity (strongly succinate dehydrogenase-reactive blood vessels) and ragged-red fibers. Cytochrome c oxidase activity in most of these reactive blood vessels and ragged-red fibers was positive. The similar morphological behavior in these vessels and fibers suggests that an increase in mutant mtDNA is responsible for mitochondrial proliferation and dysfunction in both tissues where cytochrome c oxidase is not a primarily defective enzyme. The pattern of expression of genes for mtDNA-encoded ribosomal RNA and the protein-coding region cytochrome c oxidase subunit II were similar in muscle specimens of patients with MELAS, patients with chronic progressive external ophthalmoplegia, and normal control subjects, and also between the two MELAS mutations. These results do not support the hypothesis that impaired transcription termination is a molecular defect in MELAS.
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PMID:Increased mitochondrial DNA in blood vessels and ragged-red fibers in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). 768 81

In light of the intensive genetic selection for high milk production and the onset of global warming, it seems that the reduced fertility of lactating cows during the summer will worsen in coming years. Although not entirely clear, the mechanism appears to be multifactorial in nature. It includes alterations in follicular development, depression of follicular dominance, and impairment of steroidogenesis and gonadotropin secretion. Heat-induced perturbations in the physiology of the follicle-enclosed oocyte have also been documented, expressed by impaired cleavage rate and reduced developmental competence. With respect to the oocyte, alterations include an increase in PUFA in the membrane, reactive oxygen species, ceramide formation and caspase activity, and induction of apoptosis via the sphingomyelin and/or mitochondrial pathways. New insight into cellular and molecular alterations has revealed that heat induces perturbations in both nuclear and cytoplasmic maturation events, such as resumption of meiosis, metaphase II plate formation, cytoskeleton rearrangement, and translocation of cortical granules. Alterations in mitochondrial distribution (i.e., low proportion of category I mitochondria) and function (i.e., low membrane potential) have recently been reported for oocytes collected during the summer. These were associated with impaired expression of both nuclear (succinate dehydrogenase subunit [SDHD], adenosine triphosphate [ATP] synthase subunit beta [ATP5B]), mitochondrially NADH dehydrogenase subunit 2 (ND2), and mitochondiral (cytochrome c oxidase subunit II [MT-CO2] and cytochrome b [MT-CYB]) genes that are crucial in the mitochondrial respiratory chain. In addition, season-induced alteration in the stored maternal mRNA has been documented, expressed by reduced transcript levels (oocyte maturation factor MOS [C-MOS], growth differentiation factor 9 [GDF9], POU domain class 5 transcription factor 1 [POU5F1], and glyceraldehyde-3-phosphate dehydrogenase []GAPDH) in metaphase II stage oocytes and embryos before (i.e., 2-, 4-, and 8-cell stages) and after (i.e., 8- to 16-cell stage) embryonic genome activation. Taken together, the findings indicate an association between cellular and molecular modifications and reduced developmental competence during the hot seasons. Such knowledge is essential for the development of new approaches to cope with this unsolved problem.
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PMID:PHYSIOLOGY AND ENDOCRINOLOGY SYMPOSIUM: Cellular and molecular mechanisms of heat stress related to bovine ovarian function. 2602 Feb 99