Abstract A rat fibroblastic cell line (rat-1/myc-ERtrade mark) was treated with different concentration of Antimycin A, a metabolic poison that affects mitochondrial respiratory chain complex III. The modes of cell death were analyzed by time-lapse videomicroscopy, in situ end-labeling (ISEL) technique, and ultrastructural analysis. Intracellular ATP levels were also measured in order to detect whether the energetic stores were determinant for the type of cell death. It was found that while apoptosis was the prevalent cell death in the fibroblasts treated with low doses, 100 or 200 microM Antimycin A, a new type of cell demise that shared dynamic, molecular, and morphological features with both apoptosis and necrosis represents the most common cell death when the cells were exposed to high doses, 300 or 400 microM, of the hypoxic stimulus. This new type of cell death has been chimerically termed aponecrosis. The inhibition of caspase 3, an enzyme critical for the apoptotic DNA degradation, caused a clear shift from aponecrosis to necrosis in the cell culture, suggesting that this new type of cell death could account for an incomplete execution of the apoptotic program and the following degeneration in necrosis. After being treated with higher doses, i.e., 1000 microM Antimycin A, almost all of the cells died by true necrosis. The analysis of the cellular energetic stores showed that the levels of ATP were a primary determinant in directing toward active cell death (apoptosis), aponecrosis, or necrosis. We conclude that chemically induced hypoxia produces different types of cell death depending on the intensity of the insult and on the ATP availability of the cell, and that the classic apoptosis and necrosis may represent only two extremes of a continuum of intermediate forms of cell demise.

Aponecrosis: morphologic and biochemical exploration of a syncretic process of cell death sharing apoptosis andnecrosis / Formigli L.; Papucci L.; Tani A.; Schiavone N.; Tempestini A.; Orlandini G. E.; Capaccioli S.; Zecchi Orlandini S.. - In: JOURNAL OF CELLULAR PHYSIOLOGY. - ISSN 0021-9541. - STAMPA. - 181:(2000), pp. 41-49. [10.1002/(SICI)1097-4652(200001)182:1<41::AID-JCP5>3.0.CO;2-7]

Aponecrosis: morphologic and biochemical exploration of a syncretic process of cell death sharing apoptosis andnecrosis.

FORMIGLI, LUCIA;PAPUCCI, LAURA;TANI, ALESSIA;SCHIAVONE, NICOLA;TEMPESTINI, ALESSIO;ORLANDINI, GIOVANNI;CAPACCIOLI, SERGIO;ZECCHI, SANDRA
2000

Abstract

Abstract A rat fibroblastic cell line (rat-1/myc-ERtrade mark) was treated with different concentration of Antimycin A, a metabolic poison that affects mitochondrial respiratory chain complex III. The modes of cell death were analyzed by time-lapse videomicroscopy, in situ end-labeling (ISEL) technique, and ultrastructural analysis. Intracellular ATP levels were also measured in order to detect whether the energetic stores were determinant for the type of cell death. It was found that while apoptosis was the prevalent cell death in the fibroblasts treated with low doses, 100 or 200 microM Antimycin A, a new type of cell demise that shared dynamic, molecular, and morphological features with both apoptosis and necrosis represents the most common cell death when the cells were exposed to high doses, 300 or 400 microM, of the hypoxic stimulus. This new type of cell death has been chimerically termed aponecrosis. The inhibition of caspase 3, an enzyme critical for the apoptotic DNA degradation, caused a clear shift from aponecrosis to necrosis in the cell culture, suggesting that this new type of cell death could account for an incomplete execution of the apoptotic program and the following degeneration in necrosis. After being treated with higher doses, i.e., 1000 microM Antimycin A, almost all of the cells died by true necrosis. The analysis of the cellular energetic stores showed that the levels of ATP were a primary determinant in directing toward active cell death (apoptosis), aponecrosis, or necrosis. We conclude that chemically induced hypoxia produces different types of cell death depending on the intensity of the insult and on the ATP availability of the cell, and that the classic apoptosis and necrosis may represent only two extremes of a continuum of intermediate forms of cell demise.
181
41
49
Formigli L.; Papucci L.; Tani A.; Schiavone N.; Tempestini A.; Orlandini G. E.; Capaccioli S.; Zecchi Orlandini S.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2158/356840
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