PKC-ε is upstream and PKC-α is downstream of mitoKATP channels in the signal transduction pathway of ischemic preconditioning of human myocardium

  title={PKC-$\epsilon$ is upstream and PKC-$\alpha$ is downstream of mitoKATP channels in the signal transduction pathway of ischemic preconditioning of human myocardium},
  author={Ashraf Hamed Hassouna and Bashir Mnene Matata and Manuel Gali{\~n}anes},
  journal={American Journal of Physiology-cell Physiology},
Protein kinase C (PKC) is involved in the process of ischemic preconditioning (IPC), although the precise mechanism is still a subject of debate. Using specific PKC inhibitors, we investigated whic... 

Diazoxide acts more as a PKC‐ɛ activator, and indirectly activates the mitochondrial KATP channel conferring cardioprotection against hypoxic injury

This work aimed to clarify the role of PKC isoforms and the relationship between the PKCISO forms and the mitoKATP channel in diazoxide‐induced cardioprotection.

Mitochondrial ATP-sensitive potassium channels and mitochondrial protein kinase C: sometimes it's good to have a close neighbor.

  • G. Grover
  • Biology
    American journal of physiology. Heart and circulatory physiology
  • 2006
The fine study by Jiang et al. is an important milestone in the ongoing studies on the role of the mitochondrial ATP-sensitive K+ (mitoKATP) channels in myocardial ischemia.

Signaling pathways involved in postconditioning-induced cardioprotection of human myocardium, in vitro

In conclusion, PKC activation, opening of mitoKATP channels and p38 MAPK activation in early reoxygenation induced the postconditioning of human myocardium, in vitro.

Signaling Mechanisms in Ischemic Preconditioning: Interaction of PKCε and MitoKATP in the Inner Membrane of Mitochondria

IPC is a process in which brief periods of ischemia improves the ability of the heart to tolerate subsequent prolonged ischemic periods, and the opening of a mitochondrial channel is believed to be critical for the induction of IPC.

Functional Analysis of Regulatory Phosphorylation Events in Cardiac KATP Channel Subunits in Ischaemia

It was found that PKC activator, Phorbol 12-Myristate 13-Acetate (PMA), inhibited pinacidil-activated Kir 6.1/SUR2A and Kir6.1-containing KATP channels using the whole cell patch clamp technique and the inhibitory effect of PKC was abolished in this mutant.

The Interaction of Isoflurane and Protein Kinase C-Activators on Sarcolemmal KATP Channels

It is found that exposure of isolated guinea pig cardiomyocytes to 1 mM of isoflurane after phorbol ester stimulation of PKC facilitates the induction of larger (P ≤ 0.05) sarcolemmal KATP channel currents (IKATP) during cell dialysis with 0.5, compared to 1.0, mM of ATP in the pipette.

Phospholipase C as a potential target for cardioprotection during oxidative stress.

The historical and current information on PLC-mediated signal transduction mechanisms in I/R are reviewed, as well as outlining future directions that should be addressed to extend knowledge of ischemic heart disease and improve its therapy.



Opening of mitochondrial KATP channel occurs downstream of PKC-ε activation in the mechanism of preconditioning

We examined whether the mitochondrial ATP-sensitive K channel (KATP) is an effector downstream of protein kinase C-e (PKC-e) in the mechanism of preconditioning (PC) in isolated rabbit hearts. PC w...

Protein Kinase C- ξ is Responsible for the Protection of Preconditioning in Rabbit Cardiomyocytes

It is indicated that PKC-epsilon alone is responsible for the early phase of PC's protection in rabbit cardiomyocytes and this study uses novel peptide inhibitors which correspond to part of the amino acid sequence from the isozyme-specific RACK-binding site on the PKC molecule.

Downregulation of Protein Kinase C Inhibits Activation of Mitochondrial KATP Channels by Diazoxide

It is suggested that PKC activation is required for the opening of mitoKATP channels during protection against ischemia and that this effect is linked to isoform-specific translocation of PKC-&dgr; to the mitochondria.

Implication of protein kinase C-alpha, delta, and epsilon isoforms in ischemic preconditioning in perfused rat hearts.

The ischemic preconditioning significantly improved the recovery of left ventricular developed pressure (LVDP) during reperfusion following 20 min of ischemia and the translocation of PKC-alpha, delta, epsilon isoforms suggest that one or more of these three isoforms ofPKC is involved in ischeic preconditionsing by phosphorylating membrane proteins.

Role of protein kinase C-alpha in activation of ecto-5'-nucleotidase in the preconditioned canine myocardium.

It is concluded that ischemic preconditioning activates PKC-alpha, and thus ecto-5'-nucleotidase, in the preconditionsed myocardium and this enhancement was blunted by GF109203X.

PKC-δ inhibition does not block preconditioning-induced preservation in mitochondrial ATP synthesis and infarct size reduction in rats

It is demonstrated, using a luciferase-based assay to determine the rate of ATP synthesis and state of mitochondrial bioenergetics, that IPC preserves ATP synthesis in the ischemic myocardium and that this preservation is attenuated by the isoform non-selective PKC inhibitor, chelerythrine, but not by the δ- selective antagonist, rottlerin.

Roles of mitochondrial ATP-sensitive K channels and PKC in anti-infarct tolerance afforded by adenosine A1 receptor activation.

Pharmacological and ischemic preconditioning of the human myocardium: mitoKATP channels are upstream and p38MAPK is downstream of PKC

Opening of mitoKATP channels and activation of PKC and p38MAPK are obligatory steps in the signal transduction cascade of IP and PP of the human myocardium with PKC activation being downstream of the opening of mkinase kinase channels and upstream of p38 MAPK activation.

Preconditioning of isolated rat heart is mediated by protein kinase C.

The results suggest that PKC is an effector of preconditioning in the isolated rat heart and transient ischemia and alpha 1-adrenergic receptor-induced preconditionsing is inhibited by protein kinase C (PKC) antagonists.

Signal transduction of flumazenil-induced preconditioning in myocytes.

Flumazenil mimics preconditioning to reduce cell death in cardiomyocytes and oxygen radicals activate mitochondrial K(ATP) channels via PKC during the process.