Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.3.3.1 (
citrate synthase
)
4,488
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
During embryonic and early juvenile development, endotherms must balance energy allocation between growth and heat production. Failure to either match the ATP demand of growing tissue or produce heat at the correct developmental stage will lead to damage of the organism. We tested the hypothesis that AMP-activated protein kinase (AMPK) is involved in the regulation of energy metabolism and heat production during development in the chicken (Gallus gallus). We show that mRNA concentrations of regulatory and catalytic AMPK subunits, AMPK total protein, and AMPK phosphorylation increase during development [3 days (-3 days) and one day (-1 day) before hatching, and +1 day and +8 days after hatching] in liver, and to a lesser extent in skeletal muscle. Chronic stimulation with 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) significantly increases AMPK phosphorylation in skeletal muscle and in liver. This increase was paralleled by significant increases in heat production, glucose utilization, and liver and skeletal muscle mitochondrial capacity (
citrate synthase
activity). The effects of AMPK are likely to be mediated by inhibition of acetyl CoA carboxylase (ACC) after hatching, when ACC protein concentration increases significantly, and by a significant AMPK-induced increase in PGC-1alpha mRNA concentration (at +1 day), but not in NRF-1 mRNA concentration. AMPK phosphorylation is under the control of thyroid hormone, and AMPK phosphorylation decreases significantly following the induction of
hypothyroidism
. We propose AMPK as a principal regulatory mechanism during the transition from ectothermy to endothermy in birds, and show that AMPK function in birds is similar to that observed in mammals.
...
PMID:AMP-activated protein kinase controls metabolism and heat production during embryonic development in birds. 2080 19
Hypothyroidism
(
Hypo
) is a risk factor for cardiovascular diseases, including heart failure.
Hypo
rapidly induces Ca
2+
mishandling and contractile dysfunction (CD), as well as atrophy and ventricular myocytes (VM) remodeling.
Hypo
decreases SERCA-to-phospholamban ratio (SERCA/PLB), and thereby contributes to CD. Nevertheless, detailed spatial and temporal Ca
2+
cycling characterization in VM is missing, and contribution of other structural and functional changes to the mechanism underlying Ca
2+
mishandling and CD, as transverse tubules (T-T) remodeling, mitochondrial density (D
mit
) and energy availability, is unclear. Therefore, in a rat model of
Hypo
, we aimed to characterize systolic and diastolic Ca
2+
signaling, T-T remodeling, D
mit
,
citrate synthase
(CS) activity and high-energy phosphate metabolites (ATP and phosphocreatine). We confirmed a decrease in SERCA/PLB (59%), which slowed SERCA activity (48%), reduced SR Ca
2+
(19%) and blunted Ca
2+
transient amplitude (41%). Moreover, assessing the rate of SR Ca
2+
release (dRel/dt), we found that early and maximum dRel/dt decreased, and this correlated with staggered Ca
2+
transients. However, dRel/dt persisted during Ca
2+
transient relaxation due to abundant late Ca
2+
sparks. Isoproterenol significantly up-regulated systolic Ca
2+
cycling. T-T were unchanged, hence, cannot explain staggered Ca
2+
transients and altered dRel/dt. Therefore, we suggest that these might be caused by RyR2 clusters desynchronization, due to diminished Ca
2+
-dependent sensitivity of RyR2, which also caused a decrease in diastolic SR Ca
2+
leak. Furthermore, D
mit
was unchanged and CS activity slightly decreased (14%), however, the ratio phosphocreatine/ATP did not change, therefore, energy deficiency cannot account for Ca
2+
and contractility dysregulation. We conclude that decreased SR Ca
2+
, due to slower SERCA, disrupts systolic RyR2 synchronization, and this underlies CD.
...
PMID:Underlying mechanism of the contractile dysfunction in atrophied ventricular myocytes from a murine model of hypothyroidism. 2974 31
<< Previous
1
2
