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Published on: September 7, 2018
HSC73-tubulin complex formation during low-flow ischemia in the canine myocardium
Robert S Decker1, Marlene L Decker, Sakie Nakamura
1Feinberg Cardiovascular Research Institute, Northwestern University, The Feinberg School of Medicine, Chicago, Illinois 60611-3008, USA. r-decker@northwestern.edu
Insights
Heat shock protein 73 (HSC73) interacts with tubulin, protecting microtubules in canine heart cells during low-flow ischemia. This interaction helps limit cellular damage in viable cardiomyocytes.
Area of Science:
- Cardiovascular Biology
- Cellular Biology
- Biochemistry
Background:
- The microtubule cytoskeleton is crucial for cardiomyocyte structure and function.
- Heat shock proteins, including HSP70 family members, play roles in cellular stress response.
- Understanding these interactions is key to protecting the heart during ischemic events.
Purpose of the Study:
- To investigate the interplay between the microtubule cytoskeleton and heat shock protein 70 (HSP70) in cardiomyocytes during low-flow ischemia.
- To identify the specific roles of HSP70 family members, particularly HSP73 (HSC73), in maintaining microtubule integrity.
Main Methods:
- Induction of moderate (50% flow reduction for 2h) and severe (75% flow reduction for 5h) low-flow ischemia in canine myocardium, followed by reperfusion.
- Utilized electron microscopy and immunofluorescence microscopy to assess microtubule structure and protein localization.
- Analyzed the colocalization of HSC73 with tubulin and microtubule structures.
Main Results:
- Low-flow ischemia caused partial to near-complete depolymerization of intermyofibrillar microtubules and dissolution of the perinuclear microtubule girdle.
- Centrosomal tubulin arrays remained intact.
- HSC73 colocalized with intact microtubules and perinuclear/centrosomal tubulin in moderately ischemic cells.
- Microtubule depolymerization and tubulin-HSC73 complexes were observed in severely ischemic tissue.
Conclusions:
- HSC73 directly interacts with tubulin in cardiomyocytes.
- HSC73 may protect specific microtubule network elements during reversible low-flow ischemia.
- This interaction potentially limits myofibril disruption and preserves cardiomyocyte viability under ischemic stress.
Abstract:
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.
