Influence of agents that alter lysosomal function on fetal mouse hearts recovering from anoxia and substrate depletion.
Recovery of fetal mouse heart myocytes from oxygen and substrate deprivation for 1 h is accompanied by complicated lysosomal and non-lysosomal vacuolar responses which can be subdivided temporally into four distinct phases that include production of lysosomal dense bodies; segregation of damaged subcellular organelles into vacuoles that initially lack lysosomal enzymes; delivery of lysosomal enzymes to these vacuoles through fusion with dense bodies, transforming them into lysosomal autophagic vacuoles and degradation of the sequestered organelles. These events are normally completed within 6 h of the resupply of oxygen and substrate. The progression of these events is influenced significantly by pharmacological interventions that alter lysosomal properties. Chloroquine inhibits all aspects of the lysosomally-related processes as well as the sequestration phase during recovery. Leupeptin delays the lysosomal degradation, presumably by slowing proteolysis. Hydrocortisone permits the engulfment phase and the appearance of lysosomal dense bodies but appears to prevent or postpone the delivery of lysosomal enzymes to many of the large vacuoles and to delay the degradation of sequestered organelles. These observations reveal that segregation of damaged organelles and lysosomally-mediated degradation of these subcellular structures are important events during recovery from ischemic-like injury, and that agents that interfere with normal lysosomal function can prevent or delay some or all of the lysosomal responses that are involved in the recovery process.
D000818:Animals; D002738:Chloroquine / Q000494:pharmacology*; D005260:Female; D005333:Fetus; D006854:Hydrocortisone / Q000494:pharmacology*; D000860:Hypoxia / Q000473:pathology*; D007700:Kinetics; D007976:Leupeptins / Q000494:pharmacology*; D008247:Lysosomes / Q000187:drug effects / Q000648:ultrastructure*; D051379:Mice; D008854:Microscopy, Electron; D009206:Myocardium / Q000648:ultrastructure*; D009842:Oligopeptides / Q000494:pharmacology*; D009924:Organ Culture Techniques; D011247:Pregnancy; D014617:Vacuoles / Q000187:drug effects / Q000648:ultrastructure
D007976:Leupeptins; D009842:Oligopeptides; D002738:Chloroquine; C032854:leupeptin; D006854:Hydrocortisone