Nitric oxide (NO) is believed to be an effector molecule that mediates interleuMn (IL)-1β-induced destruction and dysfunction of pancreatic β-cells. We have demonstrated that both exogenous NO and NO generated endogenously by IL-1β brought about apoptosis of isolated rat pancreatic islet cells as well as pancreatic β-cell tumorderived cell line HIT. This apoptosis was characterized by cleavage of DNA into nucleosomal fragments of 180–200 bp and morphologically by nuclear shrinkage, chromatic condensation, and apoptotic body formation. The EL-1β-induced internucleosomal DNA cleavage occurred in a time- and dose-dependent manner. Actinomycin D, cycloheximide, and nitric oxide synthase inhibitors inhibited the DNA cleavage, which was correlated with the amount of NO produced, indicating that NO produced by HIT cells themselves could mediate the apoptosis. Furthermore, in the presence of tumor necrosis factor (TNF)-α, large amounts of NO were produced by IL-1β and DNA cleavage occurred more noticeably, although TNF-β alone did not generate NO. Streptozotocin (STZ), a diabetogenic reagent containing a nitroso moiety, also released NO and induced internucleosomal DNA cleavage in HIT cells. These results suggest that NO-induced internucleosomal DNA cleavage is an important initial step in the destruction and dysfunction of pancreatic (β-cells induced by inflammatory stimulation or treatment with STZ.
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Original Articles|
July 01 1995
Apoptotic Cell Death Triggered by Nitric Oxide in Pancreatic β-Cells
Hideaki Kaneto;
Hideaki Kaneto
Department of Internal Medicine, Osaka University School of Medicine
Osaka
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Junichi Fujii;
Junichi Fujii
Department of Biochemistry, Osaka University School of Medicine
Osaka
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Han Geuk Seo;
Han Geuk Seo
Department of Biochemistry, Osaka University School of Medicine
Osaka
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Keiichiro Suzuki;
Keiichiro Suzuki
Department of Biochemistry, Osaka University School of Medicine
Osaka
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Taka-aki Matsuko;
Taka-aki Matsuko
Department of Internal Medicine, Osaka University School of Medicine
Osaka
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Nakamura Masahiro;
Nakamura Masahiro
Department of Anatomy, Sapporo Medical College
Sapporo, Japan
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Haruyuki Tatsumi;
Haruyuki Tatsumi
Department of Biochemistry, Osaka University School of Medicine
Osaka
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Yoshimitsu Yamasaki;
Yoshimitsu Yamasaki
Department of Internal Medicine, Osaka University School of Medicine
Osaka
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Takenobu Kamada;
Takenobu Kamada
Department of Internal Medicine, Osaka University School of Medicine
Osaka
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Naoyuki Taniguchi
Naoyuki Taniguchi
Department of Biochemistry, Osaka University School of Medicine
Osaka
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Address correspondence and reprint requests to Naoyuki Taniguchi, Osaka University School of Medicine, 2–2 Yamadaoka, Suita, Osaka 565, Japan.
Diabetes 1995;44(7):733–738
Article history
Received:
September 06 1994
Revision Received:
March 23 1995
Accepted:
March 23 1995
PubMed:
7540572
Citation
Hideaki Kaneto, Junichi Fujii, Han Geuk Seo, Keiichiro Suzuki, Taka-aki Matsuko, Nakamura Masahiro, Haruyuki Tatsumi, Yoshimitsu Yamasaki, Takenobu Kamada, Naoyuki Taniguchi; Apoptotic Cell Death Triggered by Nitric Oxide in Pancreatic β-Cells. Diabetes 1 July 1995; 44 (7): 733–738. https://doi.org/10.2337/diab.44.7.733
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