کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2515540 1118530 2007 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Agonist-stimulated reactive oxygen species formation regulates β2-adrenergic receptor signal transduction
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی داروشناسی
پیش نمایش صفحه اول مقاله
Agonist-stimulated reactive oxygen species formation regulates β2-adrenergic receptor signal transduction
چکیده انگلیسی

Generation of reactive oxygen species (ROS) can occur upon agonist stimulation of surface receptors to modulate downstream signaling processes. Here, we show that activation of the β2 adrenergic receptor (β2AR) by stimulation with the agonist isoproterenol leads to generation of ROS that is required for β2AR signal transduction. Specifically, we show that inhibition of NADPH oxidase with diphenyliodonium chloride, inhibition of the small GTPase Rac1 with NSC23766, and inhibition of formed ROS with the antioxidant N-acetyl-l-cysteine decreases β2AR-mediated cAMP formation, protein kinase A activation, and receptor phosphorylation and internalization, but does not impact ligand binding. The results also show that inhibition of ROS attenuates active β2AR-mediated binding of GTP to α subunits of heterotrimeric G proteins. Based on these results, we propose that agonist-dependent ROS formation is needed for β2AR signal transduction, perhaps through stabilization of active receptor conformers by redox-mediated modification of receptor and/or Gα proteins cysteine residues.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 74, Issue 1, 30 June 2007, Pages 64–73
نویسندگان
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