Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.3.1 (citrate synthase)
 4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thyroid hormone (TH) induces marked changes in the biochemical and physiological functioning of cardiac muscle affecting its bioenergetics, contractility and structure. Using a time-course analysis of in vitro treatment of neonatal rat cardiomyocytes with triiodothyronine (T3), mitochondrial biogenesis, functional bioenergetics and cardiomyocyte hypertrophic phenotype were assessed. Activity of respiratory complexes II, IV, V and citrate synthase (CS), levels of mitochondrial enzyme subunits (e.g. COXI, COXIV) and nuclear-encoded transcription factors, involved in mitochondrial biogenesis (e.g. PGC-1, mtTFA and PPAR-alpha), were significantly elevated with 72 h T3 treatment. A time-course analysis showed an early increase (between 3 and 12 h) in activity and levels of subunits of complex IV and V, mitochondrial Ca2+ accumulation and a late increase (at 72 h) in complex II and CS activities, mitochondrial protein content and mitochondrial respiration. Based on overall protein content and specific peptide levels (e.g. actin or myosin) only mild cardiomyocyte hypertrophy was detected. T3 mediates an early stimulation of enzymes containing mtDNA encoded subunits (e.g. complex IV and V) in contrast to a different regulatory pattern for the entirely nuclear-encoded enzymes (e.g. CS and complex II). T3-regulation was similar in both neonatal and young adult cardiomyocytes (ARCM) but absent in the senescent cardiomyocytes. This model offer an opportunity to study the rapid timing of events involved in myocardial cell signaling, bioenergetics and growth dynamics in a timeframe not available with whole animal studies.
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PMID:Nuclear-mitochondrial cross-talk in cardiomyocyte T3 signaling: a time-course analysis. 1589 63

Creatine kinase (CK) is a phosphotransfer kinase that catalyzes the reversible transfer of a phosphate moiety between ADP and creatine and that is highly expressed in skeletal muscle. In fast glycolytic skeletal muscle, deletion of the cytosolic M isoform of CK in mice (M-CK-/-) leads to a massive increase in the oxidative capacity and of mitochondrial volume. This study was aimed at investigating the transcriptional pathways leading to mitochondrial biogenesis in response to CK deficiency. Wild type and M-CK-/- mice of eleven months of age were used for this study. Gastrocnemius muscles of M-CK-/- mice exhibited a dramatic increase in citrate synthase (+120%) and cytochrome oxidase (COX, +250%) activity, and in mitochondrial DNA (+60%), showing a clear activation of mitochondrial biogenesis. Similarly, mRNA expression of the COXI (mitochondria-encoded) and COXIV (nuclear-encoded) subunits were increased by +103 and +94% respectively. This was accompanied by an increase in the expression of the nuclear respiratory factor (NRF2alpha) and the mitochondrial transcription factor (mtTFA). Expression of the co-activator PGC-1alpha, a master gene in mitochondrial biogenesis was not significantly increased while that of PGC-1beta and PRC, two members of the same family, was moderately increased (+45% and +55% respectively). While the expression of the modulatory calcineurin-interacting protein 1 (MCIP1) was dramatically decreased (-68%) suggesting inactivation of the calcineurin pathway, the metabolic sensor AMPK was activated (+86%) in M-CK-/- mice. These results evidence that mitochondrial biogenesis in response to a metabolic challenge exhibits a unique pattern of regulation, involving activation of the AMPK pathway.
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PMID:Mitochondrial biogenesis in fast skeletal muscle of CK deficient mice. 1805 21