I kappa B overexpression in cardiomyocytes prevents NF-kappa B translocation and provides cardioprotection in trauma.
This study examined the effects of either IkappaBalpha overexpression (transgenic mice) or N-acetyl-leucinyl-leucinyl-norleucinal (ALLN) administration (proteosome inhibitor in wild-type mice) on cardiomyocyte secretion of tumor necrosis factor-alpha (TNF-alpha) and on cardiac performance after burn trauma. Transgenic mice were divided into four experimental groups. IkappaBalpha overexpressing mice were given a third-degree scald burn over 40% of the total body surface area or wild-type littermates were given either a scald or sham burn to provide appropriate controls. Pharmacological studies included ALLN (20 mg/kg) administration in either burned wild-type mice or wild-type shams. Burn trauma in wild-type mice promoted nuclear factor-kappaB (NF-kappaB) nuclear translocation, cardiomyocyte secretion of TNF-alpha, and impaired cardiac performance. IkappaBalpha overexpression or ALLN treatment of burn trauma prevented NF-kappaB activation in cardiac tissue, prevented cardiomyocyte secretion of TNF-alpha, and ablated burn-mediated cardiac contractile dysfunction. These data suggest that NF-kappaB activation and inflammatory cytokine secretion play a significant role in postburn myocardial abnormalities.
Carlson
Deborah L
DL
Department of Surgery, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9160, USA.
White
D Jean
DJ
Maass
David L
DL
Nguyen
Robin C
RC
Giroir
Brett
B
Horton
Jureta W
JW
D000818:Animals; D002056:Burns / Q000188:drug therapy / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000627:therapeutic use; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D005260:Female; D020672:I-kappa B Proteins / Q000096:biosynthesis* / Q000235:genetics; D007976:Leupeptins / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009200:Myocardial Contraction / Q000187:drug effects / Q000235:genetics; D032383:Myocytes, Cardiac / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism; D014947:Wounds and Injuries / Q000188:drug therapy / Q000378:metabolism*
D015853:Cysteine Proteinase Inhibitors; D016207:Cytokines; D020672:I-kappa B Proteins; D007976:Leupeptins; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D014409:Tumor Necrosis Factor-alpha; C063261:acetylleucyl-leucyl-norleucinal; D000072000:NF-KappaB Inhibitor alpha