INTRACELLULAR CALCIUM, DNASE ACTIVITY AND MYOCYTE APOPTOSIS IN AGING FISCHER 344 RATS

Abstract Myocyte apoptosis increases with age in Fischer 344 rats, but the multiple molecular events implicated in this phenomenon remain to be identified. Several defects involving Ca 2+ homeostasis, pH, and the expression of p53 and genes of the Bcl-2 protein family may contribute to the activation of myocyte death. Therefore, changes in intracellular pH, cytosolic Ca 2+ , DNase I and DNase II were measured in myocytes isolated by enzymatic digestion from rats of different ages. Moreover, the expression of p53, Bcl-2 and Bax in these cells was determined. Measurements of intracellular pH by BCECF fluorescence at 3, 12 and 24 months showed that this parameter did not change with age: 3 months, 7.20±0.05; 12 months, 7.21±0.07; 24 months, 7.18±0.09. In contrast, diastolic Ca 2+ determined by the Fura 2-AM method increased progressively from 99.8±1.9 n m at 3 months to 136.3±9.6 n m at 24 months ( P P