کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6021890 | 1580654 | 2014 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The BCL-2 family protein Bid is critical for pro-inflammatory signaling in astrocytes
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کلمات کلیدی
IKKSMI-32Inhibitor of kappaB kinaseBH3-only proteinSOD1G93ABcl-2 Family ProteinAPAF1NOD1IFNγNF-κBSOD1IL-1βGFAPPNDNEMOBH3 Interacting Domain Death Agonist - BH3 تعامل دامنه آگونیست مرگIba-1 - IBA-1Astrocyte - آستروسیتamyotrophic lateral sclerosis - اسکلروز جانبی آمیوتروفیکinterferon-γ - اینترفرون-γInterleukin-1β - اینترلوکین-1βALS - بیماری اسکلروز جانبی آمیوتروفیکTransgenic - تراریختهmotoneuron degeneration - دژنراسیون مونئورونpost-natal day - روز بعد از تولدsuperoxide dismutase 1 - سوپر اکسید دیسموتاز 1apoptotic protease activating factor 1 - عامل فعال آپوپتوز پروتئاز 1nuclear factor-kappaB - فاکتور هسته ای - kappaBnuclear factor-κB - فاکتور هسته ای κBionized calcium-binding adapter molecule 1 - ملکول آداپتور اتصال دهنده کلسیم یونیزه 1wild-type - نوع وحشیGlial fibrillary acidic protein - پروتئین اسیدی فیبریلاسیون گلایالBID - پیشنهاد
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
عصب شناسی
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چکیده انگلیسی
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motoneurons in the spinal cord, brainstem and motor cortex. Mutations in the superoxide dismutase 1 (SOD1) gene represent a frequent genetic determinant and recapitulate a disease phenotype similar to ALS when expressed in mice. Previous studies using SOD1G93A transgenic mice have suggested a paracrine mechanism of neuronal loss, in which cytokines and other toxic factors released from astroglia or microglia trigger motoneuron degeneration. Several pro-inflammatory cytokines activate death receptors and may downstream from this activate the Bcl-2 family protein, Bid. We here sought to investigate the role of Bid in astrocyte activation and non-cell autonomous motoneuron degeneration. We found that spinal cord Bid protein levels increased significantly during disease progression in SOD1G93A mice. Subsequent experiments in vitro indicated that Bid was expressed at relatively low levels in motoneurons, but was enriched in astrocytes and microglia. Bid was strongly induced in astrocytes in response to pro-inflammatory cytokines or exposure to lipopolysaccharide. Experiments in bid-deficient astrocytes or astrocytes treated with a small molecule Bid inhibitor demonstrated that Bid was required for the efficient activation of transcription factor nuclear factor-κB in response to these pro-inflammatory stimuli. Finally, we found that conditioned medium from wild-type astrocytes, but not from bid-deficient astrocytes, was toxic when applied to primary motoneuron cultures. Collectively, our data demonstrate a new role for the Bcl-2 family protein Bid as a mediator of astrocyte activation during neuroinflammation, and suggest that Bid activation may contribute to non-cell autonomous motoneuron degeneration in ALS.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 70, October 2014, Pages 99-107
Journal: Neurobiology of Disease - Volume 70, October 2014, Pages 99-107
نویسندگان
Hans-Georg König, Karen S. Coughlan, Sinéad Kinsella, Bridget A. Breen, Jochen H.M. Prehn,