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: UNIPROT:P20020 (
adenosine triphosphatase
)
3,299
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Increased sarcoplasmic reticulum (SR) Ca
2+
leak via the cardiac ryanodine receptor (
RyR2
) has been suggested to play a mechanistic role in the development of heart failure (HF) and cardiac arrhythmia. Mice treated with a selective
RyR2
stabilizer, rycal S36, showed normalization of SR Ca
2+
leak and improved survival in pressure overload (PO) and myocardial infarction (MI) models. The development of HF, measured by echocardiography and molecular markers, showed no difference in rycal S36- versus placebo-treated mice. Reduction of SR Ca
2+
leak in the PO model by the rycal-unrelated
RyR2
stabilizer dantrolene did not mitigate HF progression. Development of HF was not aggravated by increased SR Ca
2+
leak due to
RyR2
mutation (R2474S) in volume overload, an SR Ca
2+
leak-independent HF model. Arrhythmia episodes were reduced by rycal S36 treatment in PO and MI mice in vivo and ex vivo in Langendorff-perfused hearts. Isolated cardiomyocytes from murine failing hearts and human ventricular failing and atrial nonfailing myocardium showed reductions in delayed afterdepolarizations, in spontaneous and induced Ca
2+
waves, and in triggered activity in rycal S36 versus placebo cells, whereas the Ca
2+
transient, SR Ca
2+
load, SR Ca
2+
adenosine triphosphatase
function, and action potential duration were not affected. Rycal S36 treatment of human induced pluripotent stem cells isolated from a patient with catecholaminergic polymorphic ventricular tachycardia could rescue the leaky
RyR2
receptor. These results suggest that SR Ca
2+
leak does not primarily influence contractile HF progression, whereas rycal S36 treatment markedly reduces ventricular arrhythmias, thereby improving survival in mice.
...
PMID:Sarcoplasmic reticulum calcium leak contributes to arrhythmia but not to heart failure progression. 3062 13
Hypothyroidism is associated with profound left ventricular dysfunction. Triiodothyronine (T
3
) supplementation may improve cardiac function after ischemic reperfusion (I/R) injury. In the present study, the effect of T
3
on major calcium cycling proteins and high-energy phosphate content during I/R was evaluated. Isolated perfused rat hearts were divided into 5 groups: Sham Control (Sham, n=10), Control (n=8), T
3
10 nM (T
3
-10, n=10), T
3
25 nM (T
3
-25, n=10) and T
3
50 nM (T
3
-50, n=10). T
3
was administrated for 60 min before 30 min of ischemia and 120 min of reperfusion. The protein contents of Ca
2+
-release channels (
RyR2
), Ca
2+
-
adenosine triphosphatase
(SERCA2a), phospholamban (PLB), sarcolemmal Ca
2+
-
adenosine triphosphatase
(PMCA) and sodium-calcium exchanger (NCX), as well as the high-energy phosphate content in heart tissues were measured by western blot analysis. The results revealed that T
3
improved the contractile recovery (left ventricular developed pressure; +dP/dt, -dP/dt) after I/R. Western blotting assays demonstrated that I/R depressed the contents of RYR2, SERCA2a and phosphorylated RYR2 and PLB; there were no effects on the contents of PLB, PMCA and NCX. T
3
reversed I/R-induced degradation of
RyR2
and SERCA2a, restored the phosphorylation of
RyR2
and PLB, and preserved the high-energy phosphate contents of ATP and creatine phosphate. T
3
supplementation protected the heart against I/R injury via the preservation of Ca
2+
-cycling proteins and high-energy phosphate content.
...
PMID:Cardioprotective effects of triiodothyronine supplementation against ischemia reperfusion injury by preserving calcium cycling proteins in isolated rat hearts. 3179 15
