title: 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.affiliation: Dept. of Surgery, East Tennessee State Univ., Campus Box 70575, Johnson City, TN 37614-0575, USA.
authors.forename: Tuanzhu
authors.initials: T
authors.lastname: Ha
authors.forename: Fang
authors.initials: F
authors.lastname: Hua
authors.forename: Daniel
authors.initials: D
authors.lastname: Grant
authors.forename: Yeling
authors.initials: Y
authors.lastname: Xia
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.forename: Jim
authors.initials: J
authors.lastname: Kelley
authors.forename: David L
authors.initials: DL
authors.lastname: Williams
authors.forename: John
authors.initials: J
authors.lastname: Kalbfleisch
authors.forename: I William
authors.initials: IW
authors.lastname: Browder
authors.forename: Race L
authors.initials: RL
authors.lastname: Kao
authors.forename: Chuanfu
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D005936:Glucans / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D019746:Intramolecular Oxidoreductases; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D018805:Sepsis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology; D018487:Ventricular Dysfunction, Left / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control
chemical_list: D005936:Glucans; D008263:Macrophage Migration-Inhibitory Factors; D019253:Proto-Oncogene Proteins c-bcl-2; C480175:glucan phosphate; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse