کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8479196 | 1551295 | 2014 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
3,5,4â²-Trihydroxy-6,7,3â²-trimethoxyflavone protects astrocytes against oxidative stress via interference with cell signaling and by reducing the levels of intracellular reactive oxygen species
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کلمات کلیدی
CREBAchillea fragrantissima2′7′-dichlorofluorescein diacetateDPPHDCF-DACAAHSQCABAPERKTTFnuclear magnetic resonance - رزونانس مغناطیسی هستهایMAPK - MAPKMitogen activated protein kinase kinase - Mitogen فعال پروتئین کیناز کینازROS - ROSSAPK/JNK - SAPK / JNKHydrogen peroxide - آب اکسیژنهstress-activated protein kinase/c-Jun N-terminal kinase - استنتاج پروتئین کیناز / c-Jun N-terminal kinaseNMR - تشدید مغناطیسی هستهای CNS - دستگاه عصبی مرکزیcentral nervous system - سیستم عصبی مرکزیextracellular signal regulated kinase - سیگنال خارج سلولی kinase را تنظیم می کندHeteronuclear single quantum coherence spectroscopy - طیف سنجی تک هسته ای تک هسته ای کوانتومیcorrelation spectroscopy - طیف سنجی همبستگیheteronuclear multiple-bond correlation spectroscopy - طیف سنجی همبستگی چند باند هترونیکی هسته ایCellular antioxidant activity - فعالیت آنتی اکسیدانی سلولیMEK - مجاهدین خلقHMBC یا Heteronuclear Multiple Bond Correlation - همبستگی پیوند چندگانه ناجورهستهH2O2 - هیدروژن پراکسیدcyclic AMP response element-binding protein - پروتئین اتصال دهنده عنصر Response Cyclic AMPmitogen-activated protein kinase - پروتئین کیناز فعال با mitogenCOSY - کثیفReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Oxidative stress is tightly involved in various neurodegenerative diseases such as Parkinson's and Alzheimer's diseases, and conditions such as ischemia. Astrocytes, the most abundant glial cells in the brain, protect neurons from reactive oxygen species (ROS) and provide them with trophic support. Therefore, any damage to astrocytes will affect neuronal survival. In a previous study we have demonstrated that an extract prepared from the plant Achillea fragrantissima (Af) prevented the oxidative stress-induced death of astrocytes and attenuated the intracellular accumulation of ROS in astrocytes under oxidative stress. In the present study, using activity guided fractionation, we have purified from this plant the active compound, determined to be a flavonoid named 3,5,4â²-trihydroxy-6,7,3â²-trimethoxyflavone (TTF). The effects of TTF in any biological system have not been studied previously, and this is the first study to characterize the anti-oxidant and protective effects of this compound in the context of neurodegenerative diseases. Using primary cultures of astrocytes we have found that TTF prevented the hydrogen peroxide (H2O2)-induced death of astrocytes, and attenuated the intracellular accumulation of ROS following treatment of these cells with H2O2 or the peroxyl radicals generating molecule 2,2â²-Azobis(amidinopropane) (ABAP). TTF also interfered with cell signaling events and inhibited the phosphorylation of the signaling proteins stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), extracellular signal regulated kinase (ERK 1/2) and mitogen activated protein kinase kinase (MEK1) and the phosphorylation of the transcription factor cyclic AMP response element-binding protein (CREB). The mechanism of the protective effect of TTF against H2O2-cytotoxicity could not be attributed to a direct H2O2 scavenging but rather to the scavenging of free radicals as was shown in cell free systems. Thus, TTF might be a therapeutic candidate for the prevention/treatment of neurodegenerative diseases where oxidative stress is part of the pathophysiology.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurochemistry International - Volume 78, December 2014, Pages 67-75
Journal: Neurochemistry International - Volume 78, December 2014, Pages 67-75
نویسندگان
Anat Elmann, Alona Telerman, Sharon Mordechay, Hilla Erlank, Miriam Rindner, Rivka Ofir, Yoel Kashman,