Nitric oxide triggers programmed cell death (apoptosis) of adult rat ventricular myocytes in culture
| Autor: | Kim E. Olson, Youping Liu, Yi Ming Yang, David J. Pinsky, Richard P. Kline, Matthias Szabolcs, Paul J. Cannon, Eleni Athan, Walif Aji |
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| Rok vydání: | 1999 |
| Předmět: |
Male
medicine.medical_specialty Programmed cell death Physiology Heart Ventricles Apoptosis Biology Nitric Oxide Nitric oxide Pathogenesis chemistry.chemical_compound Physiology (medical) Internal medicine medicine Myocyte Animals Ventricular Function Nitric Oxide Donors Rats Wistar Cells Cultured Penicillamine Cell biology Rats Endocrinology chemistry Circulatory system S-Nitroso-N-acetylpenicillamine Cardiology and Cardiovascular Medicine medicine.drug |
| Zdroj: | The American journal of physiology. 277(3) |
| ISSN: | 0002-9513 |
| Popis: | Excessive nitric oxide (NO) production within the heart is implicated in the pathogenesis of myocyte death, but the mechanism whereby NO kills cardiac myocytes is not known. To determine whether NO may trigger programmed cell death (apoptosis) of adult rat ventricular myocytes in culture, the NO donor S-nitroso- N-acetylpenicillamine (SNAP) was shown to kill purified cardiac myocytes in a dose-dependent fashion. In situ analysis of ventricular myocytes plated on chamber slides using nick-end labeling of DNA demonstrated that SNAP induces cardiac myocyte apoptosis, which was confirmed by the identification of oligonucleosomal DNA fragmentation on agarose gel electrophoresis. Similarly, treatment of cardiac myocytes with cytokines that induce inducible NO synthase was shown to cause an NO-dependent induction of apoptosis. Addition of reduced hemoglobin to scavenge NO liberated by SNAP extinguished both the increase in percentage of apoptotic cells and the appearance of DNA ladders. Treatment with SNAP (but not with N-acetylpenicillamine or SNAP + hemoglobin) not only induced apoptosis but resulted in a marked increase in p53 expression in cardiac myocytes detected by Western blotting and immunohistochemistry. These data indicate that NO has the capacity to kill cardiac myocytes by triggering apoptosis and suggest the involvement of p53 in this process. |
| Databáze: | OpenAIRE |
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