کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2567452 | 1128330 | 2010 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Nitric oxide induces apoptosis in GM-CSF-treated eosinophils via caspase-6-dependent lamin and DNA fragmentation
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
پزشکی ریوی و تنفسی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Nitric oxide induces apoptosis in GM-CSF-treated eosinophils via caspase-6-dependent lamin and DNA fragmentation Nitric oxide induces apoptosis in GM-CSF-treated eosinophils via caspase-6-dependent lamin and DNA fragmentation](/preview/png/2567452.png)
چکیده انگلیسی
Asthma is characterized by accumulation of eosinophils in the lungs and delayed apoptosis may be one mechanism leading to eosinophilia. Nitric oxide (NO), present in inflamed lungs, has been shown to possess both anti- and proeosinophilic properties. We previously showed that NO induces apoptosis in the presence of survival prolonging cytokine IL-5 in human eosinophils. In the present study, we examined the intracellular mechanisms of NO-induced apoptosis in granulocyte macrophage-colony stimulating factor (GM-CSF)-treated eosinophils concentrating on the role of caspases and calpains. Eosinophils were isolated from human blood and apoptosis was determined by relative DNA fragmentation assay, morphological analysis and/or Annexin-V FITC assay. We showed that NO-donor S-nitroso-N-acetyl-d,l-penicillamine (SNAP) induced apoptosis in GM-CSF-treated eosinophils. SNAP-induced DNA fragmentation was totally prevented by an inhibitor of caspase-6 (Z-VEID-FMK). Decreased levels of caspase-6 proenzyme and increased amounts of cleaved lamin A/C in SNAP-treated cells indicated activation of caspase-6. Furthermore, SNAP-induced lamin A/C and B fragmentation was totally abolished by an inhibitor of caspase-6. According to our results, caspase-6 mediates lamin and DNA fragmentation also in spontaneously dying eosinophils. Inhibitor of calpains prevented most of DNA fragmentation related to spontaneous apoptosis but had no effect in eosinophils undergoing NO-induced apoptosis. In the present study we showed that caspase-6 is essential for the executive phase involving lamin and DNA fragmentation in both NO-induced and spontaneous eosinophil apoptosis. However, differences in the involvement of calpains suggest that the intracellular signalling in NO-induced apoptosis has specific features at the level of proteases. This study demonstrates new mechanisms for NO-induced and spontaneous apoptosis in human eosinophils.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Pulmonary Pharmacology & Therapeutics - Volume 23, Issue 4, August 2010, Pages 365-371
Journal: Pulmonary Pharmacology & Therapeutics - Volume 23, Issue 4, August 2010, Pages 365-371
نویسندگان
Pinja Ilmarinen-Salo, Eeva Moilanen, Hannu Kankaanranta,