Effects of burn injury on myocardial signaling and cytokine secretion: Possible role of PKC.

Abstract

This study examined the effects of major burn injury on the cellular distribution of several PKC isoforms in adult rat hearts and examined the hypothesis that PKC plays a regulatory role in cardiomyocyte cytokine secretion. Burn trauma was given over 40% total body surface area in Sprague-Dawley rats. An in vitro model of burn injury included addition of burn serum, 10% by volume, to primary cardiomyocyte cultures (collagen perfusion). In vivo burn injury produced redistribution of PKCdelta, PKCepsilon, and PKCalpha from the cytosol (soluble) to the membrane (particulate) component of the myocardium. This activation of the PKC isoforms was evident 2 h after burn injury and progressively increased over 24 h postburn. Addition of burn serum to isolated myocytes produced similar PKC isoform redistribution from the soluble to the particulate compartment, promoted myocyte Ca2+ and Na+ loading, and promoted robust myocyte secretion of inflammatory cytokines similar to that reported after in vivo burn injury. Pretreating cardiomyocytes with either calphostin or PKCepsilon inhibitory peptide, a potent inhibitor of PKCepsilon, prevented burn serum-related redistribution of the PKCepsilon isoform and prevented burn serum-related cardiomyocyte secretion of TNF-alpha, IL-1beta, IL-6, and IL-10. These data suggest that the PKCepsilon isoform plays a pivotal role in myocardial inflammatory response to injury, altering cardiac function by modulating cardiomyocyte inflammatory cytokine response to injury.

• Authors: Jing Tan, David L Maass, D Jean White, Jureta W Horton
• Journal: American journal of physiology. Regulatory, integrative and comparative physiology (Am J Physiol Regul Integr Comp Physiol) Vol. 292 Issue 2 Pg. R887-96 (Feb 2007) ISSN: 0363-6119 [Print] United States
• PMID: 16990486 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Cytokines
• Enzyme Inhibitors
• Isoenzymes
• Muscle Proteins
• Naphthalenes
• calphostin complex
• Sodium
• Protein Kinase C
• Protein Kinase C-alpha
• Protein Kinase C-delta
• Protein Kinase C-epsilon
• Calcium

Topics

• Animals
• Blotting, Western
• Burns (blood, physiopathology)
• Calcium (metabolism, physiology)
• Cell Membrane (metabolism)
• Cell Separation
• Cells, Cultured
• Cytokines (metabolism)
• Cytosol (metabolism)
• Enzyme Inhibitors (pharmacology)
• Heart (physiopathology)
• Isoenzymes (physiology)
• Male
• Muscle Proteins (biosynthesis, physiology)
• Myocardium (enzymology, metabolism)
• Myocytes, Cardiac (metabolism, physiology)
• Naphthalenes (pharmacology)
• Protein Kinase C (antagonists & inhibitors, biosynthesis, physiology)
• Protein Kinase C-alpha (physiology)
• Protein Kinase C-delta (physiology)
• Protein Kinase C-epsilon (physiology)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (physiology)
• Sodium (metabolism, physiology)