Myocardial preconditioning against ischemia-induced apoptosis and necrosis in man.

Abstract

BACKGROUND:

Ischemic preconditioning (IPC) protects against apoptosis and necrosis but the contribution of the two forms of cell death and whether the beneficial effects are mediated by similar or different signal transduction pathways remains unclear. Here we have investigated the effect of IPC on the type of cell death in the human heart and whether the inhibition of apoptosis and necrosis by IPC requires the opening of mitoK(ATP) channels and the activation of PKC and p38MAPK.

MATERIALS AND METHODS AND RESULTS:

Free-hand tissue sections (n = 6/group) obtained from the right atrium of patients at the time of coronary bypass surgery were subjected to 90-min simulated ischemia followed by 120-min reoxygenation (SI/R) with or without IPC (5 min SI/5 min R) prior to SI/R. IPC reduced apoptosis from 30.0 +/- 3.8 to 11.0 +/- 1.5% (P < 0.05) by TUNEL technique and necrosis from 11.6 +/- 2.4 to 4.2 +/- 1.7% (P < 0.05) by propidium iodide staining. When inhibitors of mitoKATP channels (1 mm 5-hydroxydecanoate), PKC (10 microm chelerythrine), and p38MAPK (10 microm SB203580) were added for 10 min before SI, the protection against necrosis was abolished. However, whereas 5-hydroxydecanoate and chelerythrine also abolished the protection of IPC against apoptosis, SB203580 did not. The activation of mitoKATP channels (100 microm diazoxide), PKC (1 microm PMA), and p38MAPK (1 nm anisomycin) were a mirror image of the findings with blockers.

CONCLUSIONS:

IPC protects the human myocardium against both apoptosis and necrosis. The anti-necrotic effect is mediated by the opening of mitoKATP channels and activation of PKC and p38MAPK; however, the anti-apoptotic effect requires opening of the mitoKATP channels and PKC activation but is p38MAPK-independent.

• Authors: Hunaid A Vohra, Manuel Galiñanes
• Journal: The Journal of surgical research (J Surg Res) Vol. 134 Issue 1 Pg. 138-44 (Jul 2006) ISSN: 0022-4804 [Print] United States
• PMID: 16488439 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Potassium Channels
• mitochondrial K(ATP) channel
• Protein Kinase C
• p38 Mitogen-Activated Protein Kinases
• Creatine Kinase

Topics

• Apoptosis
• Creatine Kinase (metabolism)
• Humans
• Ischemic Preconditioning, Myocardial
• Male
• Myocardium (pathology)
• Necrosis
• Potassium Channels (physiology)
• Protein Kinase C (physiology)
• p38 Mitogen-Activated Protein Kinases (physiology)