Monophosphoryl lipid A protects adult rat cardiac myocytes with induction of the 72-kD heat shock protein: a cellular model of pharmacologic preconditioning.
We examined the in vitro preconditioning effect of non-toxic derivative of endotoxin, monophosphoryl lipid A (MLA) in adult rat cardiac myocytes. Cultured 5-7-day-old myocytes were preconditioned for 4 h by treatment with 200 ng/ml MLA. Twenty h later, cells were subjected to simulated ischemia by incubation in 0.75 mm sodium hydrosulfite, 12 mM KCl, 20 mM dl-lactic acid and 10 mM 2-deoxy-D-glucose (pH 6.5) for 2 h. MLA caused a significant reduction in the levels of LDH from 286+/-8 units/l in controls to 165+/-5 units/l (mean+/-s.e.m.; P<0.0001). Similarly, CK significantly decreased from 104+/-3.1 in controls to 85+/-1.4 U/l (P<0.001). Western blot analysis indicated a significant accumulation of 72 kD heat shock protein in MLA treated as compared to control cells. No changes in 27, 32, and 90 kD heat shock proteins were discernible in the MLA treated group. These data suggest a significant "anti-ischemic" effect of MLA in myocytes that is accompanied by induction of 72 kD heat shock protein.
Nayeem
M A
MA
Eric Lipman Laboratories of Molecular and Cellular Cardiology, Division of Cardiology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298, USA.
Elliott
G T
GT
Shah
M R
MR
Hastillo-Hess
S L
SL
Kukreja
R C
RC
D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects*; D050884:HSP72 Heat-Shock Proteins; D006321:Heart / Q000187:drug effects*; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D019157:Ischemic Preconditioning, Myocardial; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology; D017202:Myocardial Ischemia / Q000235:genetics / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D051381:Rats
D002317:Cardiovascular Agents; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D008050:Lipid A; C048436:monophosphoryl lipid A