کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10748398 | 1050273 | 2016 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The oxindole Syk inhibitor OXSI-2 blocks nigericin-induced inflammasome signaling and pyroptosis independent of potassium efflux
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کلمات کلیدی
LPSIL-1βNLRP3MrOSROS - ROSInflammasome - التهابinflammation - التهاب( توروم) Interleukin-1 beta - اینترلوکین-1 بتاTyrosine kinase - تیروزین کینازlipopolysaccharide - لیپوپلی ساکاریدPotassium - پتاسیمpyroptosis - پریپتوزیسmitochondrial reactive oxygen species - گونه های اکسیژن واکنش پذیر میتوکندریReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The inflammasome is a caspase-1-activating complex that is implicated in a growing number of acute and chronic pathologies. Interest has increased in identifying small molecular inhibitors of inflammasome signaling because of its role in clinically relevant diseases. It was recently reported that the protein tyrosine kinase, Syk, regulates pathogen-induced inflammasome signaling by phosphorylating a molecular switch on the adapter protein ASC. However, several aspects of the role of Syk in inflammasome signaling and the effects of its inhibition remain unclear. The aim of the present study is to explore in detail the effects of the oxindole Syk inhibitor OXSI-2 on various aspects of nigericin-induced inflammasome signaling. Our results indicate that OXSI-2 inhibits inflammasome assembly, caspase-1 activation, IL-1β processing and release, mitochondrial ROS generation, and pyroptotic cell death. Using a novel live cell potassium sensor we show that Syk inhibition with OXSI-2 has no effect on potassium efflux kinetics and that blockade of potassium efflux with extracellular potassium alters Syk phosphorylation. The effects of OXSI-2 identified in this study provide context for the role of Syk in inflammasome signaling and demonstrate its importance in oxidative signaling upstream of inflammasome activation and downstream of ion flux.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 472, Issue 3, 8 April 2016, Pages 545-550
Journal: Biochemical and Biophysical Research Communications - Volume 472, Issue 3, 8 April 2016, Pages 545-550
نویسندگان
Jordan R. Yaron, Mounica Y. Rao, Sandhya Gangaraju, Liqiang Zhang, Xiangxing Kong, Fengyu Su, Yanqing Tian, Honor L. Glenn, Deirdre R. Meldrum,