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Pharmacological and ischemic preconditioning of the human myocardium: mitoK(ATP) channels are upstream and p38MAPK is downstream of PKC.

Loubani M, Galiñanes M - BMC Physiol. (2002)

Bottom Line: Similar protection was obtained with alpha1 agonist phenylephrine, adenosine and IP and their combination did not afford additional cardioprotection.Furthermore, the protection induced by PMA was abolished by SB203580 but not by 5-hydroxydecanoate, whereas the protection induced by anisomycin was unaffected by either 5-hydroxydecanoate or chelerythrine.Opening of mitoK(ATP) 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 mitoK(ATP) channels and upstream of p38MAPK activation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Integrative Human Cardiovascular Physiology and Functional Genomics, Division of Cardiac Surgery, University of Leicester, Glenfield Hospital, Groby Road, Leicester. mahmoud.loubani@ntlworld.com

ABSTRACT

Background: These studies investigate the role of mitoK(ATP) channels, protein kinase C (PKC) and Mitogen activated protein kinase (p38MAPK) on the cardioprotection of ischemic (IP) and pharmacological preconditioning (PP) of the human myocardium and their sequence of activation.

Results: Right atrial appendages from patients undergoing elective cardiac surgery were equilibrated for 30 min and then subjected to 90 min of simulated ischemia followed by 120 min reoxygenation. At the end of each protocol creatinine kinase leakage (CK U/g wet wt) and the reduction of MTT to formazan dye (mM/g wet wt) were measured. Similar protection was obtained with alpha1 agonist phenylephrine, adenosine and IP and their combination did not afford additional cardioprotection. Blockade of mitoK(ATP) channels with 5-hydroxydecanoate, PKC with chelerythrine, or p38MAPK with SB203580 abolished the protection of IP and of PP. In additional studies, the stimulation of mitoK(ATP) channels with diazoxide or activation of PKC with PMA or p38MAPK with anisomycin induced identical protection to that of IP and PP. The protection induced by diazoxide was abolished by blockade of PKC and by blockade of p38MAPK. Furthermore, the protection induced by PMA was abolished by SB203580 but not by 5-hydroxydecanoate, whereas the protection induced by anisomycin was unaffected by either 5-hydroxydecanoate or chelerythrine.

Conclusions: Opening of mitoK(ATP) 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 mitoK(ATP) channels and upstream of p38MAPK activation.

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Creatine Kinase (CK) leakage into the media (A) during the 120 min reoxygenation period and MTT reduction by the slices (B) at the end of the reoxygenation period in human atrial myocardium subjected to various protocols (see Figure 1) to investigate the efficacy of preconditioning via α1-adrenoreceptors or adenosine receptors alone and in combination with IP (Study 1). Data are expressed as mean ± SEM of six experiments. *p < 0.05 vs SI/R alone group.
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Figure 4: Creatine Kinase (CK) leakage into the media (A) during the 120 min reoxygenation period and MTT reduction by the slices (B) at the end of the reoxygenation period in human atrial myocardium subjected to various protocols (see Figure 1) to investigate the efficacy of preconditioning via α1-adrenoreceptors or adenosine receptors alone and in combination with IP (Study 1). Data are expressed as mean ± SEM of six experiments. *p < 0.05 vs SI/R alone group.

Mentions: Figures 4A and 4B demonstrate that SI/R alone resulted in a significant increase in CK leakage and decrease in MTT reduction when compared to the aerobic controls. They also show that PP with phenylephrine or adenosine administered prior to SI/R is as protective as IP and that their use in combination does not result in additive protection.


Pharmacological and ischemic preconditioning of the human myocardium: mitoK(ATP) channels are upstream and p38MAPK is downstream of PKC.

Loubani M, Galiñanes M - BMC Physiol. (2002)

Creatine Kinase (CK) leakage into the media (A) during the 120 min reoxygenation period and MTT reduction by the slices (B) at the end of the reoxygenation period in human atrial myocardium subjected to various protocols (see Figure 1) to investigate the efficacy of preconditioning via α1-adrenoreceptors or adenosine receptors alone and in combination with IP (Study 1). Data are expressed as mean ± SEM of six experiments. *p < 0.05 vs SI/R alone group.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC117790&req=5

Figure 4: Creatine Kinase (CK) leakage into the media (A) during the 120 min reoxygenation period and MTT reduction by the slices (B) at the end of the reoxygenation period in human atrial myocardium subjected to various protocols (see Figure 1) to investigate the efficacy of preconditioning via α1-adrenoreceptors or adenosine receptors alone and in combination with IP (Study 1). Data are expressed as mean ± SEM of six experiments. *p < 0.05 vs SI/R alone group.
Mentions: Figures 4A and 4B demonstrate that SI/R alone resulted in a significant increase in CK leakage and decrease in MTT reduction when compared to the aerobic controls. They also show that PP with phenylephrine or adenosine administered prior to SI/R is as protective as IP and that their use in combination does not result in additive protection.

Bottom Line: Similar protection was obtained with alpha1 agonist phenylephrine, adenosine and IP and their combination did not afford additional cardioprotection.Furthermore, the protection induced by PMA was abolished by SB203580 but not by 5-hydroxydecanoate, whereas the protection induced by anisomycin was unaffected by either 5-hydroxydecanoate or chelerythrine.Opening of mitoK(ATP) 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 mitoK(ATP) channels and upstream of p38MAPK activation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Integrative Human Cardiovascular Physiology and Functional Genomics, Division of Cardiac Surgery, University of Leicester, Glenfield Hospital, Groby Road, Leicester. mahmoud.loubani@ntlworld.com

ABSTRACT

Background: These studies investigate the role of mitoK(ATP) channels, protein kinase C (PKC) and Mitogen activated protein kinase (p38MAPK) on the cardioprotection of ischemic (IP) and pharmacological preconditioning (PP) of the human myocardium and their sequence of activation.

Results: Right atrial appendages from patients undergoing elective cardiac surgery were equilibrated for 30 min and then subjected to 90 min of simulated ischemia followed by 120 min reoxygenation. At the end of each protocol creatinine kinase leakage (CK U/g wet wt) and the reduction of MTT to formazan dye (mM/g wet wt) were measured. Similar protection was obtained with alpha1 agonist phenylephrine, adenosine and IP and their combination did not afford additional cardioprotection. Blockade of mitoK(ATP) channels with 5-hydroxydecanoate, PKC with chelerythrine, or p38MAPK with SB203580 abolished the protection of IP and of PP. In additional studies, the stimulation of mitoK(ATP) channels with diazoxide or activation of PKC with PMA or p38MAPK with anisomycin induced identical protection to that of IP and PP. The protection induced by diazoxide was abolished by blockade of PKC and by blockade of p38MAPK. Furthermore, the protection induced by PMA was abolished by SB203580 but not by 5-hydroxydecanoate, whereas the protection induced by anisomycin was unaffected by either 5-hydroxydecanoate or chelerythrine.

Conclusions: Opening of mitoK(ATP) 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 mitoK(ATP) channels and upstream of p38MAPK activation.

Show MeSH
Related in: MedlinePlus