Isoproterenol-induced redistribution of endosomes in cardiac myocytes.
During myocardial infarction, it is well known that the cytoplasm of cardiac myocytes becomes more acidic due to lactate accumulation. The resulting necrosis is believed to result, at least in part, from the leakage of lysosomal enzymes into the cytoplasm. In addition, it has previously been shown that cytoplasm acidification in tissue culture cells can cause the redistribution of late endosomes and tubular lysosomes. In the present study, we have investigated whether lysosomal/endosomal structures were affected during isoproterenol-induced infarct-like myocardial necrosis in rat heart in vivo. In parallel, we treated rat primary myocyte cultures with a high dose of isoproterenol or low pH. We followed the fate of lysosomal enzymes, a lysosomal membrane glycoprotein and the cation-independent mannose 6-phosphate receptor. Lysosomes were intact until irreversible injury became evident suggesting that the lysosomal enzyme release concomitant with the leakage of cytoplasmic enzymes is merely a consequence of cell death. During the early phase of injury, when the myocyte cytoplasm was mildly acidified, late endosomes showed fragmentation and microtubule-dependent movement towards the periphery, while the subcellular distribution of lysosomes was unchanged. Both processes were also observed after mild artificial acidification of the cytoplasm. Our data show that late endosomes and lysosomal trafficking are affected early during isoproterenol-induced myocardial injury causing a pH-dependent redistribution of late endosomes.
Marjomäki
V
V
Department of Biology, University of Jyväskylä, Finland.
Ritamäki
V
V
Gruenberg
J
J
D000818:Animals; D002478:Cells, Cultured; D011992:Endosomes / Q000187:drug effects*; D005629:Frozen Sections; D006321:Heart / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D007545:Isoproterenol / Q000494:pharmacology*; D008247:Lysosomes / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology*; D009206:Myocardium / Q000648:ultrastructure*; D009336:Necrosis; D051381:Rats; D017208:Rats, Wistar
D007545:Isoproterenol