کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9015258 | 1127147 | 2005 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Chloroquine induces the expression of inducible nitric oxide synthase in C6 glioma cells
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کلمات کلیدی
NF-κBl-NACPC-PLCATF-2PKCFCSpKaiNOSLPSDMEMDulbecco's modified Eagle Medium - Eagle Medium اصلاح شده DulbeccoMAPK - MAPKMAPK/ERK kinase - MAPK / ERK kinasep38 MAPK - P38 MAPKROS - ROSfetal calf serum - سرم گوساله جنینC6 glioma cells - سلولهای گلیوما C6inducible nitric oxide synthase - سنتاز اکسید نیتریک القاییnuclear factor kappa B - فاکتور هسته ای کاپا BPhosphatidylcholine-specific phospholipase C - فسفاتیدیل کولین خاص فسفولیپاز Cactivating transcription factor 2 - فعال کردن عامل رونویسی 2lipopolysaccharide - لیپوپلی ساکاریدMEK - مجاهدین خلقNitric oxide - نیتریک اکسیدprotein kinase A - پروتئین کیناز AProtein kinase C - پروتئین کیناز سیmitogen-activated protein kinase - پروتئین کیناز فعال با mitogenChloroquine - کلروکین Reactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
داروشناسی
پیش نمایش صفحه اول مقاله
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چکیده انگلیسی
Chloroquine, a well-known lysosomotropic agent, has long been used for the treatment of malaria and rheumatologic disorders. However, therapeutic doses of chloroquine are known to cause behavioral side effects. In the present study, we investigated whether chloroquine stimulates inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) synthesis in C6 glioma cells. Chloroquine caused dose-dependent increase in iNOS protein expression and NO production in C6 glioma cells. A tyrosine kinase inhibitor (genistein), a protein kinase C (PKC) inhibitor (Ro 31-8220), and a p38 mitogen-activated protein kinase (MAPK) inhibitor (SB 203580) all respectively suppressed chloroquine-induced iNOS expression and NO release from C6 glioma cells. Chloroquine activates p38 MAPK and stimulates PKC-α and -δ translocation from the cytosol to the membrane in C6 glioma cells. Chloroquine-stimulated p38 MAPK activation was blocked by genistein (20 μM), Ro 31-8220 (3 μM), and SB 203580 (10 μM). Incubation of lipopolysaccharide (LPS)-stimulated cells with chloroquine at non-toxic concentrations (10-100 μM) for 48 h increased iNOS expression, and led to a significant loss of adherent cells. Induction of DNA fragmentation in floating cells indicated that the C6 glioma cells were undergoing apoptosis. Taken together, our data suggest that chloroquine may activate tyrosine kinase and/or PKC to induce p38 MAPK activation, which in turn induces iNOS expression and NO production.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Pharmacological Research - Volume 51, Issue 4, April 2005, Pages 329-336
Journal: Pharmacological Research - Volume 51, Issue 4, April 2005, Pages 329-336
نویسندگان
Tso-Hsiao Chen, Po-Chiao Chang, Mon-Chiu Chang, Yuan-Fong Lin, Horng-Mo Lee,