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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2010.1
- 수록면
- 777 - 786 (10page)
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Endoplasmic reticulum (ER) stress regulates a wide range of cellular responses including apoptosis, proliferation,inflammation, and differentiation in mammalian cells. In this study, we observed the role of 2-deoxy-D-glucose (2DG) on inflammation of chondrocytes.
2DG is well known as an inducer of ER stress,via inhibition of glycolysis and glycosylation. Treatment of 2DG in chondrocytes considerably induced ER stress in a dose- and time-dependent manner, which was demonstrated by a reduction of glucose regulated protein of 94 kDa (grp94), an ER stress-inducible protein,as determined by a Western blot analysis. In addition,induction of ER stress by 2DG led to the expression of COX-2 protein with an apparent molecular mass of 66-70kDa as compared with the normally expressed 72-74 kDa protein. The suppression of ER stress with salubrinal (Salub), a selective inhibitor of eif2-alpha dephosphorylation, successfully prevented grp94 induction and efficiently recovered 2DGmodified COX-2 molecular mass and COX-2 activity might be associated with COX-2 N-glycosylation. Also,treatment of 2DG increased phosphorylation of Src in chondrocytes. The inhibition of the Src signaling pathway with PP2 (Src tyrosine kinase inhibitor) suppressed grp94 expression and restored COX-2 expression,N-glycosylation, and PGE2 production, as determined by a Western blot analysis and PGE2assay. Taken together, our results indicate that the ER stress induced by 2DG results in a decrease of the transcription level, the molecular mass, and the activity of COX-2 in rabbit articular chondrocytes via a Src kinase-dependent pathway.
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참고문헌 (25)
참고문헌 신청
Archer CW / 1990 / Phenotypic modulation in sub-populations of human articular chondrocytes in vitro / J Cell Sci 97 : 361 ~ 371
Aridor M / 1999 / Integration of endoplasmic reticulum signaling in health and disease / Nat Med 5 : 745 ~ 751
Brandt KD / 1998 / The importance of nonpharmacologic approaches in management of osteoarthritis / Am J Med 105 : 39S ~ 44S
Chandrasekhar S / 1988 / Interleukin-1-induced alterations in proteoglycan metabolism and matrix assembly / Arch Biochem Biophys 265 : 294 ~ 301
Chen W / 2001 / Role of p38 MAP kinases and ERK in mediating ultraviolet-B induced cyclooxygenase-2 gene expression in human keratinocytes / Oncogene 20 : 3921 ~ 3926
Aridor M / 1999 / Integration of endoplasmic reticulum signaling in health and disease / Nat Med 5 : 745 ~ 751
Brandt KD / 1998 / The importance of nonpharmacologic approaches in management of osteoarthritis / Am J Med 105 : 39S ~ 44S
Chandrasekhar S / 1988 / Interleukin-1-induced alterations in proteoglycan metabolism and matrix assembly / Arch Biochem Biophys 265 : 294 ~ 301
Chen W / 2001 / Role of p38 MAP kinases and ERK in mediating ultraviolet-B induced cyclooxygenase-2 gene expression in human keratinocytes / Oncogene 20 : 3921 ~ 3926
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