HSC73-tubulin complex formation during low-flow ischemia in the canine myocardium.
Canine myocardium was exposed to bouts of low-flow ischemia to identify the interactions that develop between the microtubule-based cytoskeleton and the heat shock protein 70 (HSP70) family of heat shock proteins in viable cardiomyocytes. "Moderate" or "severe" low-flow ischemia was produced in chronically instrumented dogs by reducing circumflex coronary flow by 50% for 2 h or by 75% for 5 h followed by reperfusion for 2 and 24 h, respectively. Electron and immunofluorescence microscopy demonstrated either partial or nearly complete depolymerization of the intermyofibrillar microtubules in areas of myofibril disruption and partial dissolution of the perinuclear microtubule girdle. In contrast, centrosomal tubulin arrays appeared to remain intact following low-flow ischemia. In cardiomyocytes displaying myofibril disruption, constitutively expressed HSP73 (HSC73) colocalized with intact but not disrupted microtubules and with perinuclear and centrosomal tubulin following moderate ischemia. Microtubule depolymerization and high molecular weight tubulin-HSC73 complexes were present in more severely ischemic tissue. These results suggest that HSC73 directly interacts with tubulin and may protect selected elements of the microtubule network and limit myofibril disruption during reversible low-flow ischemia.
Decker
Robert S
RS
Feinberg Cardiovascular Research Institute, Northwestern University, The Feinberg School of Medicine, Chicago, Illinois 60611-3008, USA. r-decker@northwestern.edu
Decker
Marlene L
ML
Nakamura
Sakie
S
Zhao
Yu-Sheng
YS
Hedjbeli
Sascha
S
Harris
Kathleen R
KR
Klocke
Francis J
FJ
D000818:Animals; D003326:Coronary Circulation / Q000502:physiology; D004285:Dogs; D005260:Female; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000032:analysis / Q000378:metabolism*; D008297:Male; D016253:Microscopy, Immunoelectron; D008870:Microtubules / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009210:Myofibrils / Q000378:metabolism; D014404:Tubulin / Q000032:analysis / Q000378:metabolism*
D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D014404:Tubulin