Cyclical mechanical stretch-induced apoptosis in myocytes from young rats but necrosis in myocytes from old rats.
Mechanical load as stimulus for apoptosis and necrosis could be responsible for the loss of cardiomyocytes. Ventricular myocytes from young (3 mo) and old (14-24 mo) rats underwent cyclical mechanical stretch (CMS; 5% elongation, 1 Hz) for 24 h. Spontaneous apoptosis was in myocytes from young rats 0.33 +/- 0.12% and from old rats 1.05 +/- 0.35% [Tdt-mediated dUTP nick-end labeling (TUNEL) assay]; associated with a decrease of Bcl-2. CMS increased the apoptosis to 0.58 +/- 0.18% in myocytes from young rats. Western blot analysis showed that CMS reduced Bcl-2 and increased p53 (young rats). Bax was not changed by CMS. These were confirmed by cytochrome c release (31 +/- 13%) and by the enrichment of cytosolic nucleosomes (11 +/- 8%). CMS did not influence the apoptosis in myocytes from old rats (TUNEL assay, Bcl-2, Bax, or p53). CMS did not cause necrosis in myocytes from young rats. CMS increased the number of necrotic cells by showing the cell membrane rupture in myocytes from old rats (50 +/- 13% 5-hexadecanoylaminofluorescein-positive and 38 +/- 6% propidium iodide-positive cells) as well as by measuring the lactate dehydrogenase release. The results suggest that CMS-induced apoptosis in myocytes of young rats but necrosis in myocytes from old rats, which could be attributed to more stress sensitivity of cells from old rats.
Husse
B
B
Department of Physiology, Martin-Luther-University Halle/Wittenberg, 6 Magdeburger St., D-06097 Halle, Germany. britta.husse@medizin.uni-halle.de
Sopart
A
A
Isenberg
G
G
D000375:Aging / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D003574:Cytochrome c Group / Q000378:metabolism; D006352:Heart Ventricles; D032383:Myocytes, Cardiac / Q000473:pathology* / Q000502:physiology*; D009336:Necrosis; D010507:Periodicity; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D013314:Stress, Mechanical; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D003574:Cytochrome c Group; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53