Glucan phosphate attenuates cardiac dysfunction and inhibits cardiac MIF expression and apoptosis in septic mice.

Abstract

Myocardial dysfunction is a major consequence of septic shock and contributes to the high mortality of sepsis. We have previously reported that glucan phosphate (GP) significantly increased survival in a murine model of cecal ligation and puncture (CLP)-induced sepsis. In the present study, we examined the effect of GP on cardiac dysfunction in CLP-induced septic mice. GP was administered to ICR/HSD mice 1 h before induction of CLP. Sham surgically operated mice served as control. Cardiac function was significantly decreased 6 h after CLP-induced sepsis compared with sham control. In contrast, GP administration prevented CLP-induced cardiac dysfunction. Macrophage migration inhibitory factor (MIF) has been implicated as a major factor in cardiomyocyte apoptosis and cardiac dysfunction during septic shock. CLP increased myocardial MIF expression by 88.3% (P < 0.05) and cardiomyocyte apoptosis by 7.8-fold (P < 0.05) compared with sham control. GP administration, however, prevented CLP-increased MIF expression and decreased cardiomyocyte apoptosis by 51.2% (P < 0.05) compared with untreated CLP mice. GP also prevented sepsis-caused decreases in phospho-Akt, phospho-GSK-3beta, and Bcl-2 levels in the myocardium of septic mice. These data suggest that GP treatment attenuates cardiovascular dysfunction in fulminating sepsis. GP administration also activates the phosphoinositide 3-kinase/Akt pathway, decreases myocardial MIF expression, and reduces cardiomyocyte apoptosis.

• Authors: Tuanzhu Ha, Fang Hua, Daniel Grant, Yeling Xia, Jing Ma, Xiang Gao, Jim Kelley, David L Williams, John Kalbfleisch, I William Browder, Race L Kao, Chuanfu Li
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 291 Issue 4 Pg. H1910-8 (Oct 2006) ISSN: 0363-6135 [Print] United States
• PMID: 16766637 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Glucans
• Macrophage Migration-Inhibitory Factors
• Proto-Oncogene Proteins c-bcl-2
• glucan phosphate
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• Intramolecular Oxidoreductases
• Mif protein, mouse

Topics

• Animals
• Apoptosis (drug effects, physiology)
• Gene Expression Regulation (drug effects, physiology)
• Glucans (pharmacology)
• Heart (drug effects, physiopathology)
• Intramolecular Oxidoreductases
• Macrophage Migration-Inhibitory Factors (genetics, metabolism)
• Male
• Mice
• Mice, Inbred ICR
• Myocardium (metabolism, pathology)
• Phosphatidylinositol 3-Kinases (genetics, metabolism)
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
• Sepsis (metabolism, pathology, physiopathology)
• Signal Transduction (physiology)
• Ventricular Dysfunction, Left (pathology, physiopathology, prevention & control)