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Autophagy in cardiac myocytes
Abstract:
The fetal mouse heart (FMH) in organ culture continues to beat for a period of weeks, but degenerative changes occur. Electron microscopy revealed formation of autophagic vacuoles containing damaged organelles in some cells after the first day, indicating focal cytoplasmic injury. This process was accelerated by transient deprivation of oxygen and glucose followed by resupply of oxygen and glucose. FMHs were maintained for up to four hours in glucose-free media in an atmosphere of 95% N/5% CO2 followed by resupply of O2 and glucose. Twenty-four hours later, many cells recovered without residual injury. Many others revealed autophagic vacuoles ranging from those in which organelles were readily identified to those characteristic of residual bodies. It appears that focal injury stimulates the endoplasmic reticulum to enclose the damaged components, permitting localized lysosomal digestion without causing injury to the entire cell. Autophagy has not been emphasized as an important mechanism in transient ischemia in adult myocytes, but it may play a role in repair of sublethal injury. The FMH organ culture provides an excellent model for studying the sequential autophagic changes in a system in which these events can be accelerated.
Insights
Fetal mouse hearts in organ culture show that autophagy repairs sublethal injury. This process, involving the endoplasmic reticulum and lysosomes, helps cells recover from transient ischemia.
Area of Science:
- Cardiovascular Biology
- Cellular Biology
- Developmental Biology
Background:
- Fetal mouse hearts (FMH) in organ culture exhibit sustained beating but undergo degenerative changes.
- Early signs of injury include the formation of autophagic vacuoles containing damaged organelles.
Purpose of the Study:
- To investigate the role of autophagy in repairing sublethal injury in the fetal mouse heart.
- To characterize the sequential autophagic changes following transient ischemia and resupply.
Main Methods:
- Organ culture of fetal mouse hearts.
- Transient deprivation of oxygen and glucose followed by reoxygenation and glucose resupply.
- Electron microscopy to observe cellular and organelle changes, particularly autophagic vacuoles.
Main Results:
- Transient ischemia accelerated the formation of autophagic vacuoles.
- Following reoxygenation and glucose resupply, many FMH cells recovered without residual injury.
- Other cells showed autophagic vacuoles in various stages, from organelle identification to residual bodies, suggesting localized repair mechanisms.
Conclusions:
- Focal injury stimulates the endoplasmic reticulum to enclose damaged components for localized lysosomal digestion.
- Autophagy may play a significant role in the repair of sublethal injury in cardiac myocytes, particularly following transient ischemia.
- The FMH organ culture system is an effective model for studying accelerated autophagic changes.