Delayed cardioprotection is associated with the sub-cellular relocalisation of ventricular protein kinase C epsilon, but not p42/44MAPK

S Wilson, W Song, K Karoly, T Ravingerova, A Vegh, J Papp, S Tomisawa, J R Parratt, N J Pyne

Research output: Contribution to journalArticle

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Abstract

Both noradrenaline administration to rats and rapid cardiac pacing in dogs induces delayed protection of the heart against ischaemia-induced ventricular arrhythmias. In an attempt to establish molecular mechanisms underlying the delayed cardioprotection, we have examined the potential role of two kinases, PKC epsilon and p42/44MAPK. These protein kinases are expressed in the ventricles of the heart and are characterised by their ability to regulate ion-flux and gene transcription. In the rat p42MAPK is predominantly localised in the high-speed supernatant fraction of the ventricle homogenate, whereas p44MAPK is enriched in the nuclear low speed pellet. A small proportion of the p42MAPK is activated even in hearts from control animals. However, neither kinase is relocalised or activated by noradrenaline administration and this provides preliminary evidence the p42/44MAPK may not play a significant role in delayed protection in this species. In contrast, noradrenaline does induce the translocation of PKC epsilon to cell membranes, a response that is sustained for up to 4 h. However, PKC epsilon is down-regulated from the cytoplasm after 24 h post noradrenaline treatment. PKC epsilon is also translocated to the membrane in dogs that have been classically pre-conditioned and cardiac paced. In the latter case, translocation of PKC epsilon from the cytoplasm to the cell membrane is evident 24 h after pacing. These results indicate that the release of endogenous mediators may either inhibit down-regulation or elicit an increase in PKC epsilon mRNA expression. Therefore, in dog heart the subcellular relocalisation of PKC epsilon persists into the 'second window' and may play a central role in the molecular mechanism governing delayed cardioprotection. It is important in the future to identify either the gene products that are induced or the target protein(s) that are phosphorylated by PKC epsilon.
LanguageEnglish
Pages225-230
Number of pages6
JournalMolecular and Cellular Biochemistry
Volume160-161
DOIs
Publication statusPublished - 1996

Fingerprint

Protein Kinase C-epsilon
Norepinephrine
Dogs
Cell membranes
Rats
Cytoplasm
Phosphotransferases
Genes
Cell Membrane
Transcription
Protein Kinases
Heart Ventricles
Cardiac Arrhythmias
Animals
Down-Regulation
Ischemia
Ions
Fluxes
Membranes
Messenger RNA

Keywords

  • animals
  • calcium-calmodulin-dependent protein kinases
  • dogs
  • enzyme activation
  • heart
  • heart rate
  • isoenzymes
  • male
  • mitogen-activated protein kinase 1
  • myocardium
  • norepinephrine
  • protein kinase C
  • protein kinase C-epsilon
  • protein-tyrosine kinases
  • rats
  • rats, sprague-dawley
  • subcellular fractions

Cite this

Wilson, S ; Song, W ; Karoly, K ; Ravingerova, T ; Vegh, A ; Papp, J ; Tomisawa, S ; Parratt, J R ; Pyne, N J. / Delayed cardioprotection is associated with the sub-cellular relocalisation of ventricular protein kinase C epsilon, but not p42/44MAPK. In: Molecular and Cellular Biochemistry. 1996 ; Vol. 160-161. pp. 225-230.
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abstract = "Both noradrenaline administration to rats and rapid cardiac pacing in dogs induces delayed protection of the heart against ischaemia-induced ventricular arrhythmias. In an attempt to establish molecular mechanisms underlying the delayed cardioprotection, we have examined the potential role of two kinases, PKC epsilon and p42/44MAPK. These protein kinases are expressed in the ventricles of the heart and are characterised by their ability to regulate ion-flux and gene transcription. In the rat p42MAPK is predominantly localised in the high-speed supernatant fraction of the ventricle homogenate, whereas p44MAPK is enriched in the nuclear low speed pellet. A small proportion of the p42MAPK is activated even in hearts from control animals. However, neither kinase is relocalised or activated by noradrenaline administration and this provides preliminary evidence the p42/44MAPK may not play a significant role in delayed protection in this species. In contrast, noradrenaline does induce the translocation of PKC epsilon to cell membranes, a response that is sustained for up to 4 h. However, PKC epsilon is down-regulated from the cytoplasm after 24 h post noradrenaline treatment. PKC epsilon is also translocated to the membrane in dogs that have been classically pre-conditioned and cardiac paced. In the latter case, translocation of PKC epsilon from the cytoplasm to the cell membrane is evident 24 h after pacing. These results indicate that the release of endogenous mediators may either inhibit down-regulation or elicit an increase in PKC epsilon mRNA expression. Therefore, in dog heart the subcellular relocalisation of PKC epsilon persists into the 'second window' and may play a central role in the molecular mechanism governing delayed cardioprotection. It is important in the future to identify either the gene products that are induced or the target protein(s) that are phosphorylated by PKC epsilon.",
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author = "S Wilson and W Song and K Karoly and T Ravingerova and A Vegh and J Papp and S Tomisawa and Parratt, {J R} and Pyne, {N J}",
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Delayed cardioprotection is associated with the sub-cellular relocalisation of ventricular protein kinase C epsilon, but not p42/44MAPK. / Wilson, S; Song, W; Karoly, K; Ravingerova, T; Vegh, A; Papp, J; Tomisawa, S; Parratt, J R; Pyne, N J.

In: Molecular and Cellular Biochemistry, Vol. 160-161, 1996, p. 225-230.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Delayed cardioprotection is associated with the sub-cellular relocalisation of ventricular protein kinase C epsilon, but not p42/44MAPK

AU - Wilson, S

AU - Song, W

AU - Karoly, K

AU - Ravingerova, T

AU - Vegh, A

AU - Papp, J

AU - Tomisawa, S

AU - Parratt, J R

AU - Pyne, N J

PY - 1996

Y1 - 1996

N2 - Both noradrenaline administration to rats and rapid cardiac pacing in dogs induces delayed protection of the heart against ischaemia-induced ventricular arrhythmias. In an attempt to establish molecular mechanisms underlying the delayed cardioprotection, we have examined the potential role of two kinases, PKC epsilon and p42/44MAPK. These protein kinases are expressed in the ventricles of the heart and are characterised by their ability to regulate ion-flux and gene transcription. In the rat p42MAPK is predominantly localised in the high-speed supernatant fraction of the ventricle homogenate, whereas p44MAPK is enriched in the nuclear low speed pellet. A small proportion of the p42MAPK is activated even in hearts from control animals. However, neither kinase is relocalised or activated by noradrenaline administration and this provides preliminary evidence the p42/44MAPK may not play a significant role in delayed protection in this species. In contrast, noradrenaline does induce the translocation of PKC epsilon to cell membranes, a response that is sustained for up to 4 h. However, PKC epsilon is down-regulated from the cytoplasm after 24 h post noradrenaline treatment. PKC epsilon is also translocated to the membrane in dogs that have been classically pre-conditioned and cardiac paced. In the latter case, translocation of PKC epsilon from the cytoplasm to the cell membrane is evident 24 h after pacing. These results indicate that the release of endogenous mediators may either inhibit down-regulation or elicit an increase in PKC epsilon mRNA expression. Therefore, in dog heart the subcellular relocalisation of PKC epsilon persists into the 'second window' and may play a central role in the molecular mechanism governing delayed cardioprotection. It is important in the future to identify either the gene products that are induced or the target protein(s) that are phosphorylated by PKC epsilon.

AB - Both noradrenaline administration to rats and rapid cardiac pacing in dogs induces delayed protection of the heart against ischaemia-induced ventricular arrhythmias. In an attempt to establish molecular mechanisms underlying the delayed cardioprotection, we have examined the potential role of two kinases, PKC epsilon and p42/44MAPK. These protein kinases are expressed in the ventricles of the heart and are characterised by their ability to regulate ion-flux and gene transcription. In the rat p42MAPK is predominantly localised in the high-speed supernatant fraction of the ventricle homogenate, whereas p44MAPK is enriched in the nuclear low speed pellet. A small proportion of the p42MAPK is activated even in hearts from control animals. However, neither kinase is relocalised or activated by noradrenaline administration and this provides preliminary evidence the p42/44MAPK may not play a significant role in delayed protection in this species. In contrast, noradrenaline does induce the translocation of PKC epsilon to cell membranes, a response that is sustained for up to 4 h. However, PKC epsilon is down-regulated from the cytoplasm after 24 h post noradrenaline treatment. PKC epsilon is also translocated to the membrane in dogs that have been classically pre-conditioned and cardiac paced. In the latter case, translocation of PKC epsilon from the cytoplasm to the cell membrane is evident 24 h after pacing. These results indicate that the release of endogenous mediators may either inhibit down-regulation or elicit an increase in PKC epsilon mRNA expression. Therefore, in dog heart the subcellular relocalisation of PKC epsilon persists into the 'second window' and may play a central role in the molecular mechanism governing delayed cardioprotection. It is important in the future to identify either the gene products that are induced or the target protein(s) that are phosphorylated by PKC epsilon.

KW - animals

KW - calcium-calmodulin-dependent protein kinases

KW - dogs

KW - enzyme activation

KW - heart

KW - heart rate

KW - isoenzymes

KW - male

KW - mitogen-activated protein kinase 1

KW - myocardium

KW - norepinephrine

KW - protein kinase C

KW - protein kinase C-epsilon

KW - protein-tyrosine kinases

KW - rats

KW - rats, sprague-dawley

KW - subcellular fractions

U2 - 10.1007/BF00240053

DO - 10.1007/BF00240053

M3 - Article

VL - 160-161

SP - 225

EP - 230

JO - Molecular and Cellular Biochemistry

T2 - Molecular and Cellular Biochemistry

JF - Molecular and Cellular Biochemistry

SN - 0300-8177

ER -