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:2.7.11.13 (
protein kinase C
)
49,245
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The gap junction protein
connexin 43
(
Cx43
) is a key player in wound healing, and inhibitors of
Cx43
, which speed epidermal wound healing, are currently in clinical trials. Here, we provide direct
in vivo
evidence that specific phosphorylation events on
Cx43
change the physiological response during wound healing. Blocking phosphorylation, through mutation of serine residues in
Cx43
at the
protein kinase C
(
PKC
) or casein kinase 1 (CK1) sites, significantly slowed the rate of wound closure
in vivo
and
in vitro
and resulted in a thicker epidermal layer after reepithelialization. Conversely, preventing
Cx43
phosphorylation by mitogen-activated protein kinases (MAPKs) through mutation significantly increased the rate of wound closure
in vivo
Defects in migration, but not proliferation, in all mutants were partially rescued
in vitro
by changing serine residues to aspartic or glutamic acid
.
These data prove that specific
Cx43
phosphorylation events play an important role at different stages of wound healing. Thus, a clear physiological understanding of the spatiotemporal regulation of kinase activation and consequent effects on gap junctions could lead to a more targeted approach to modulating
Cx43
expression during wound healing.
...
PMID:Phosphorylation of connexin 43 at MAPK, PKC or CK1 sites each distinctly alter the kinetics of epidermal wound repair. 3142 27
Ischemic postconditioning (IPoC) reduces reperfusion arrhythmias but the antiarrhythmic mechanisms remain unknown. The aim of this study was to analyze IPoC electrophysiological effects and the role played by adenosine A
1
, A
2A
and A
3
receptors,
protein kinase C
, ATP-dependent potassium (K
ATP
) channels, and
connexin 43
. IPoC reduced reperfusion arrhythmias (mainly sustained ventricular fibrillation) in isolated rat hearts, an effect associated with a transient delay in epicardial electrical activation, and with action potential shortening. Electrical impedance measurements and Lucifer-Yellow diffusion assays agreed with such activation delay. However, this delay persisted during IPoC in isolated mouse hearts in which
connexin 43
was replaced by connexin 32 and in mice with conditional deletion of
connexin 43
. Adenosine A
1
, A
2A
and A
3
receptor blockade antagonized the antiarrhythmic effect of IPoC and the associated action potential shortening, whereas exogenous adenosine reduced reperfusion arrhythmias and shortened action potential duration. Protein kinase C inhibition by chelerythrine abolished the protective effect of IPoC but did not modify the effects on action potential duration. On the other hand, glibenclamide, a K
ATP
inhibitor, antagonized the action potential shortening but did not interfere with the antiarrhythmic effect. The antiarrhythmic mechanisms of IPoC involve adenosine receptor activation and are associated with action potential shortening. However, this action potential shortening is not essential for protection, as it persisted during
protein kinase C
inhibition, a maneuver that abolished IPoC protection. Furthermore, glibenclamide induced the opposite effects. In addition, IPoC delays electrical activation and electrical impedance recovery during reperfusion, but these effects are independent of
connexin 43
.
...
PMID:Ischemic Postconditioning Reduces Reperfusion Arrhythmias by Adenosine Receptors and Protein Kinase C Activation but Is Independent of K
ATP
Channels or Connexin 43. 3177 76
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