Cytotoxicity of Peroxynitrite in Rat Pancreatic Acinar AR4–2J Cells
作者:
Naohiro Sata,
Hanne Klonowski-Stumpe,
Bing Han,
Dieter Haussinger,
Claus Niederau,
期刊:
Pancreas
(OVID Available online 1997)
卷期:
Volume 15,
issue 3
页码: 278-284
ISSN:0885-3177
年代: 1997
出版商: OVID
关键词: Peroxynitrite;AR4–2J;Glutathione;Ebselen;Apoptosis;Wild-type P53
数据来源: OVID
摘要:
Peroxynitrite (0.5–50 μM) induced dose-dependent cytotoxic effects in rat pancreatic acinar AR4–2J cells. Glutathione (2 mM) and ebselen (10 μM) partially reduced the cytotoxicity caused by 1–10 μMconcentrations of peroxynitrite. Higher concentrations (10–50 μM) of peroxynitrite induced DNA smear suggestive of necrosis, while lower concentrations (2–5 μM) induced DNA fragmentations suggestive of apoptosis. The effects of peroxynitrite on [Ca2+]ishowed a similar dose dependency. Peroxynitrite concentrations >10 μMrapidly increased [Ca2+]iin a dose-dependent manner, while concentrations <5 μMdid not affect [Ca2+]i. In contrast, the presentation of wild-type P53 was accelerated at lower concentrations of peroxynitrite (≤10 μM) but not at higher concentrations (50 μM). The present study suggests that peroxynitrite at lower concentrations (2–5 μM) induces wild-type P53 and apoptosis, which is potentially a protective response toward the DNA damage caused by peroxynitrite. On the other hand, higher concentrations of peroxynitrite (10–50 μM) rapidly increase [Ca2+]iand eventually induce necrosis.
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