Glucan Phosphate Attenuates Cardiac Dysfunction and Inhibits Cardiac Mif Expression and Apoptosis in Septic Mice.
From: Dept. of Surgery, East Tennessee State Univ., Campus Box 70575, Johnson City, TN 37614-0575, USA.
American journal of physiology. Heart and circulatory physiology
- Publish Date: Oct 2006
- ISSN: 0363-6135
- Volume: 291
- Issue: 4
- Pages: H1910-8
- Medium: Print
- Language: English
- Citation (JAMA): Ha Tuanzhu, Hua Fang, Grant Daniel, et al. Glucan Phosphate Attenuates Cardiac Dysfunction and Inhibits Cardiac Mif Expression and Apoptosis in Septic Mice.. Am. J. Physiol. Heart Circ. Physiol. Oct 2006;291:H1910-8
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.
Mesh Headings (Keywords): 1-Phosphatidylinositol 3-Kinase, Animals, Apoptosis, Gene Expression Regulation, Glucans, Heart, Intramolecular Oxidoreductases, Macrophage Migration-Inhibitory Factors, Male, Mice, Mice, Inbred ICR, Myocardium, Proto-Oncogene Proteins c-akt, Proto-Oncogene Proteins c-bcl-2, Sepsis, Signal Transduction, Ventricular Dysfunction, Left
Check for Full Text / PubMed Unique Identifier (PMID): 16766637
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.