کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2514683 1118478 2007 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Requirement for protein kinase R in interleukin-1α-stimulated effects in cartilage
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی داروشناسی
پیش نمایش صفحه اول مقاله
Requirement for protein kinase R in interleukin-1α-stimulated effects in cartilage
چکیده انگلیسی

Interleukin-1 (IL-1) has pleiotropic effects in cartilage. The interferon-induced, double stranded RNA-activated protein kinase PKR that phosphorylates eukaryotic initiation factor 2 (eIF2) α has been implicated in cytokine effects in chondrocytes. A compound was recently identified that potently suppresses PKR autophosphorylation (IC50 approximately 200 ηM) and partially restores PKR-inhibited translation in a cell-free system with significant effect in the nanomolar range. The objectives of this study were to exploit this potent PKR inhibitor to assess whether PKR kinase activity is required for catabolic and proinflammatory effects of IL-1α in cartilage and to determine whether IL-1α causes an increase in eIF2α phosphorylation that is antagonized by the PKR inhibitor. Cartilage explants were incubated with the PKR inhibitor and IL-1α. Culture media were assessed for sulfated glycosaminoglycan as an indicator of proteoglycan degradation and for prostaglandin E2. Cartilage extracts were analyzed by Western blot for cyclooxygenase-2 and phosphorylated signaling molecules. Nanomolar concentrations of the PKR inhibitor suppressed proteoglycan degradation and cyclooxygenase-2 accumulation in IL-1α-activated cartilage. The PKR inhibitor stimulated or inhibited PGE2 production with a biphasic dose response relationship. IL-1α increased the phosphorylation of both PKR and eIF2α, and nanomolar concentrations of PKR inhibitor suppressed the IL-1α-induced changes in phosphorylation. The results strongly support PKR involvement in pathways activated by IL-1α in chondrocytes.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 74, Issue 11, 3 December 2007, Pages 1636–1641
نویسندگان
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