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Intracellular calcium, DNase activity and myocyte apoptosis in aging Fischer 344 rats.
J Mol Cell Cardiol. 1998 Mar; 30(3):519-35.JM

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 Ca2+ 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 Ca2+, 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 Ca2+ determined by the Fura 2-AM method increased progressively from 99.8+/-1.9 nm at 3 months to 136.3+/-9.6 nm at 24 months (P<0.001). Concurrently, DNase I activity evaluated by plasmid digestion assay in myocytes increased 3.2-fold from 3 to 24 months (P<0.02). Conversely, pH-dependent-DNase II remained essentially constant with age. Western blotting performed on ventricular myocytes did not detect significant changes in p53, Bax and Bcl-2 proteins with age. Similarly, immunocytochemically, the fraction of myocytes labeled by p53, Bax and Bcl-2 did not change from 3 to 24 months. In conclusion, myocyte aging is characterized by an increase in diastolic calcium which may activate DNase I triggering apoptosis, independently from the expression of p53, Bax and Bcl-2 in the cells.

Authors+Show Affiliations

Department of Medicine, New York Medical College, Valhalla, NY, 10595, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9515029

Citation

Nitahara, J A., et al. "Intracellular Calcium, DNase Activity and Myocyte Apoptosis in Aging Fischer 344 Rats." Journal of Molecular and Cellular Cardiology, vol. 30, no. 3, 1998, pp. 519-35.
Nitahara JA, Cheng W, Liu Y, et al. Intracellular calcium, DNase activity and myocyte apoptosis in aging Fischer 344 rats. J Mol Cell Cardiol. 1998;30(3):519-35.
Nitahara, J. A., Cheng, W., Liu, Y., Li, B., Leri, A., Li, P., Mogul, D., Gambert, S. R., Kajstura, J., & Anversa, P. (1998). Intracellular calcium, DNase activity and myocyte apoptosis in aging Fischer 344 rats. Journal of Molecular and Cellular Cardiology, 30(3), 519-35.
Nitahara JA, et al. Intracellular Calcium, DNase Activity and Myocyte Apoptosis in Aging Fischer 344 Rats. J Mol Cell Cardiol. 1998;30(3):519-35. PubMed PMID: 9515029.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intracellular calcium, DNase activity and myocyte apoptosis in aging Fischer 344 rats. AU - Nitahara,J A, AU - Cheng,W, AU - Liu,Y, AU - Li,B, AU - Leri,A, AU - Li,P, AU - Mogul,D, AU - Gambert,S R, AU - Kajstura,J, AU - Anversa,P, PY - 1998/5/9/pubmed PY - 1998/5/9/medline PY - 1998/5/9/entrez SP - 519 EP - 35 JF - Journal of molecular and cellular cardiology JO - J Mol Cell Cardiol VL - 30 IS - 3 N2 - 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 Ca2+ 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 Ca2+, 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 Ca2+ determined by the Fura 2-AM method increased progressively from 99.8+/-1.9 nm at 3 months to 136.3+/-9.6 nm at 24 months (P<0.001). Concurrently, DNase I activity evaluated by plasmid digestion assay in myocytes increased 3.2-fold from 3 to 24 months (P<0.02). Conversely, pH-dependent-DNase II remained essentially constant with age. Western blotting performed on ventricular myocytes did not detect significant changes in p53, Bax and Bcl-2 proteins with age. Similarly, immunocytochemically, the fraction of myocytes labeled by p53, Bax and Bcl-2 did not change from 3 to 24 months. In conclusion, myocyte aging is characterized by an increase in diastolic calcium which may activate DNase I triggering apoptosis, independently from the expression of p53, Bax and Bcl-2 in the cells. SN - 0022-2828 UR - https://www.unboundmedicine.com/medline/citation/9515029/Intracellular_calcium_DNase_activity_and_myocyte_apoptosis_in_aging_Fischer_344_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-2828(97)90616-7 DB - PRIME DP - Unbound Medicine ER -