Pharmacological preconditioning of primary rat cardiac myocytes by FK506.
Pre-treatment with the immunosuppressant FK506 is shown to protect primary cardiocytes against a subsequent severe thermal or ischaemic stress. This effect is not observed with the related compounds cyclosporin A or rapamycin. It does not involve induction of the FK506 binding, heat inducible protein hsp56 or of the other heat shock proteins. In addition over-expression of hsp56 does not protect cardiac cells from severe stress in contrast to our previous results with hsp70 and hsp90. These results suggest the FK506 is acting via a novel mechanism to protect cardiac cells against cellular ischaemia which may not be related to its immunosuppressant action.
Cumming
D V
DV
Department of Molecular Pathology, University College London Medical School, United Kingdom.
Heads
R J
RJ
Coffin
R S
RS
Yellon
D M
DM
Latchman
D S
DS
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival; D016572:Cyclosporine / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D009206:Myocardium / Q000378:metabolism*; D011090:Polyenes / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D020123:Sirolimus; D013312:Stress, Physiological / Q000378:metabolism / Q000517:prevention & control*; D016559:Tacrolimus / Q000008:administration & dosage*; D022021:Tacrolimus Binding Proteins; D014343:Trypan Blue
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D007166:Immunosuppressive Agents; D011090:Polyenes; D016572:Cyclosporine; D000469:Alkaline Phosphatase; D022021:Tacrolimus Binding Proteins; D014343:Trypan Blue; D020123:Sirolimus; D016559:Tacrolimus