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:2.7.11.17 (
CaMKII
)
4,029
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Overstimulation of the renin-angiotensin system (RAS) has been implicated in the pathogenesis of various cardiovascular diseases. Alamandine is a peptide newly identified as a protective component of the RAS; however, the mechanisms involved in its beneficial effects remain elusive. By using a well-characterized rat model of hypertension, the
TGR
(mREN2)27, we show that mREN ventricular myocytes are prone to contractile enhancement mediated by short-term alamandine (100 nmol/L) stimulation of Mas-related G protein-coupled receptor member D (MrgD) receptors, while Sprague-Dawley control cells showed no effect. Additionally, alamandine prevents the Ca
2+
dysregulation classically exhibited by freshly isolated mREN myocytes. Accordingly, alamandine treatment of mREN myocytes attenuated Ca
2+
spark rate and enhanced Ca
2+
reuptake to the sarcoplasmic reticulum. Along with these findings, KN-93 fully inhibited the alamandine-induced increase in Ca
2+
transient magnitude and phospholamban (PLN) phosphorylation at Thr17, indicating
CaMKII
as a downstream effector of the MrgD signaling pathway. In mREN ventricular myocytes, alamandine treatment induced significant nitric oxide (NO) production. Importantly, NO synthase inhibition prevented the contractile actions of alamandine, including PLN-Thr17 phosphorylation at the
CaMKII
site, thereby indicating that NO acts upstream of
CaMKII
in the alamandine downstream signaling. Altogether, our results show that enhanced contractile responses mediated by alamandine in cardiomyocytes from hypertensive rats occur through a NO-dependent activation of
CaMKII
.
...
PMID:Alamandine enhances cardiomyocyte contractility in hypertensive rats through a nitric oxide-dependent activation of CaMKII. 3191 3
