scholarly journals The Calcium Component of Gonadotropin-Releasing Hormone-Stimulated Luteinizing Hormone Subunit Gene Transcription Is Mediated by Calcium/Calmodulin-Dependent Protein Kinase Type II

Endocrinology ◽  
2003 ◽  
Vol 144 (6) ◽  
pp. 2409-2416 ◽  
Author(s):  
Daniel J. Haisenleder ◽  
Heather A. Ferris ◽  
Margaret A. Shupnik
Keyword(s):  
Protein Kinase ◽  
Gene Transcription ◽  
Calcium Influx ◽  
Critical Role ◽  
Type Ii ◽  
Subunit Gene ◽  
Dependent Protein Kinase ◽  
Α Subunit ◽  
Calcium Calmodulin Dependent ◽  
Dependent Protein

Abstract Calcium influx plays a critical role in GnRH regulation of rat LH subunit gene transcription, but the site(s) of action are undefined. We investigated the potential of GnRH acting through calcium to activate calcium/calmodulin-dependent protein kinase type II (Ca/CaMK II) in mouse gonadotrope-derived LβT2 cells. GnRH stimulated Ca/CaMK II β subunit activity 3-fold 2 min after treatment and returned to control values by 45 min. The Ca/CaMK II response to GnRH was blocked by administration of the Ca/CaMK II-specific inhibitor, KN-93. The calcium channel activator Bay K 8644 stimulated a 3-fold increase in Ca/CaMK II activity, similar to GnRH. Blocking calcium influx with nimodipine or depleting intracellular calcium storage pools with thapsigargin each resulted in a partial suppression of GnRH-induced activation of Ca/CaMK II, and in combination, completely suppressed the Ca/CaMK II response to GnRH. KN-93 and nimodipine also suppressed α-subunit and LHβ promoter responses to GnRH by 40–60%. LHβ promoter constructs containing either proximal or proximal and distal GnRH-responsive regions were sensitive to inhibition. These data show for the first time that Ca/CaMK II activation plays an important role in the transmission of GnRH signals from the plasma membrane to the LH subunit genes.

P6344Volume overload-triggered pathological myocardial remodeling occurs in the absence of calcium/calmodulin-dependent protein kinase type II delta

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Elkenani ◽  
B A Mohamed ◽  
E Buchholz ◽  
D Lbik ◽  
M Schnelle ◽  
...  
Keyword(s):  
Heart Failure ◽  
Protein Kinase ◽  
Heart Weight ◽  
Type Ii ◽  
Myocardial Remodeling ◽  
Dependent Protein Kinase ◽  
Mortality Pattern ◽  
Calcium Calmodulin Dependent ◽  
Dependent Protein ◽  
The Impact

Abstract Background Calcium/calmodulin-dependent protein kinase type II delta (CamKIIδ), the predominant cardiac CaMKII isoform, has been implicated in the progression of myocardial infarction- and pressure overload-induced pathological remodeling and heart failure, but its role in volume overload (VO) has not been defined. We have previously reported an activation of CamKII during transition to HF in VO. Purpose Here, we analyzed the impact of CamKIIδ deletion in VO-triggered myocardial remodeling and heart failure development. Methods CaMKIIδ knockout (CaMKIIδ-KO) and wild-type (WT) littermates were exposed to aorto-caval shunt-induced VO, and the progression of myocardial remodeling was assessed by serial echocardiography, histological and molecular analyses. Results CaMKIIδ-KO and WT littermates exhibited similar mortality pattern in response to VO. Serial echocardiographic measurements showed a comparable eccentric myocardial remodeling, altered left ventricle geometry and perturbed ventricular function after shunt. At 12 weeks post-shunt both CaMKIIδ-KO and WT mice experienced comparable increases in relative heart weight, cardiomyocyte diameter, cardiac apoptosis, and hypertrophic genes expression. Conclusion We therefore conclude that CaMKIIδ signaling is dispensable for the progression of pathological cardiac remodeling induced by VO. This should be considered before CaMKII inhibition is approved therapeutically for HF treatment.

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