scholarly journals A 14-3-3 Mode-1 Binding Motif Initiates Gap Junction Internalization During Acute Cardiac Ischemia

Traffic ◽  
2014 ◽  
Vol 15 (6) ◽  
pp. 684-699 ◽  
Author(s):  
James W. Smyth ◽  
Shan-Shan Zhang ◽  
Jose M. Sanchez ◽  
Samy Lamouille ◽  
Jacob M. Vogan ◽  
...  
Keyword(s):  
Gap Junction ◽  
Cardiac Ischemia ◽  
Binding Motif ◽  
Acute Cardiac Ischemia

Abstract 336: A 14-3-3 Mode-1 Binding Motif Promotes Gap Junction Internalization During Acute Cardiac Ischemia

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
James W Smyth ◽  
Jose M Sanchez ◽  
Samy Lamouille ◽  
Ting-Ting Hong ◽  
Jacob M Vogan ◽  
...  
Keyword(s):  
Gap Junction ◽  
Protein Trafficking ◽  
Connexin 43 ◽  
Electrical Coupling ◽  
Acute Ischemia ◽  
Binding Motif ◽  
Wild Type ◽  
Gap Junction Coupling ◽  
Junction Coupling ◽  
Cell Cell

During each heartbeat, robust cell-cell electrical coupling via connexin 43 (Cx43) gap junctions allows billions of individual cardiomyocytes to contract in synchrony. Cx43 turns over rapidly, and altered Cx43 trafficking during disease contributes to the arrhythmias of sudden cardiac death. The overall phosphorylation status of the Cx43 protein is known to regulate gap junction coupling, but the role of many residue specific phosphorylation events remains unknown. One such residue, Ser373, forms a mode-1 14-3-3 binding motif upon phosphorylation. Given that 14-3-3 proteins are known to regulate protein trafficking, we hypothesized a role for Cx43 Ser373 phosphorylation in regulation of Cx43 gap junction coupling. Using Langendorff-perfused mouse hearts we find robust phosphorylation of Cx43 at Ser373 and Ser368 after 30 min of no-flow ischemia. In human cell lines, a S373A mutation ablated Cx43/14-3-3 complexing and 35 S pulse-chase revealed Cx43 S373A also experiences a longer half-life than wild-type Cx43. Previous reports have implicated phosphorylation of Cx43 Ser368 in PKC mediated Cx43 internalization. We find that upon activation of PKC, the Cx43 S373A mutant undergoes lower and more transient levels of phosphorylation at Ser368 than wild-type Cx43. Consistent with these data, siRNA-mediated ablation of 14-3-3 expression results in enlargement of gap junction plaque formation at cell-cell borders. In conclusion, we propose that phosphorylation of Cx43 Ser373 results in 14-3-3 binding which promotes and maintains phosphorylation of Cx43 Ser368 and the subsequent internalization of gap junction channels. These results identify for the first time a specific role for 14-3-3 proteins in regulation of Cx43 internalization during acute ischemia and contribute to the development of therapies aimed at preserving or enhancing gap junction coupling in the heart.

Resolution of an Acute Cardiac Ischemia After the Removal of a Surgical Drain in Mitral and Tricuspid Valve Repair

2011 ◽  
Vol 91 (6) ◽  
pp. e94 ◽  
Author(s):  
Giuseppe Iaci ◽  
Alessandro Castiglioni ◽  
Andrea Fumero ◽  
Mauro Carlino ◽  
Alberto Margonato ◽  
...  
Keyword(s):  
Tricuspid Valve ◽  
Cardiac Ischemia ◽  
Tricuspid Valve Repair ◽  
Valve Repair ◽  
Acute Cardiac Ischemia ◽  
Surgical Drain

Diagnosis of acute cardiac ischemia

2003 ◽  
Vol 21 (1) ◽  
pp. 27-59 ◽  
Author(s):  
J.Hector Pope ◽  
Harry P Selker
Keyword(s):  
Cardiac Ischemia ◽  
Acute Cardiac Ischemia

Central apnea and acute cardiac ischemia in a sheep model of epileptic sudden death

1997 ◽  
Vol 42 (4) ◽  
pp. 588-594 ◽  
Author(s):  
S. Claiborne Johnston ◽  
Ralf Siedenberg ◽  
Jeffrey K. Min ◽  
E. Heidi Jerome ◽  
Kenneth D. Laxer
Keyword(s):  
Sudden Death ◽  
Cardiac Ischemia ◽  
Central Apnea ◽  
Sheep Model ◽  
Acute Cardiac Ischemia

Missed Diagnoses of Acute Cardiac Ischemia in the Emergency Department

2000 ◽  
Vol 342 (16) ◽  
pp. 1163-1170 ◽  
Author(s):  
J. Hector Pope ◽  
Tom P. Aufderheide ◽  
Robin Ruthazer ◽  
Robert H. Woolard ◽  
James A. Feldman ◽  
...  
Keyword(s):  
Emergency Department ◽  
Cardiac Ischemia ◽  
Acute Cardiac Ischemia ◽  
Missed Diagnoses
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