Protein phosphorylation on tyrosine restores expression and glycosylation of cyclooxygenase-2 by 2-deoxy-D-glucose-caused endoplasmic reticulum stress in rabbit articular chondrocyte

Abstract

2-deoxy-D-glucose(2DG)-caused endoplasmic reticulum (ER)stress inhibits protein phosphorylation at tyrosine residues. However, the accurate regulatory mechanisms, which determine the inflammatory response of chondrocytes to ER stress via protein tyrosine phosphorylation, have not been systematically evaluated. Thus, in this study, we examined whether protein phosphorylation at tyrosine residues can modulate the expression and glycosylation of COX-2, which is reduced by 2DG-induced ER stress. We observed that protein tyrosine phosphatase (PTP) inhibitors, sodium orthovanadate (SOV), and phenylarsine oxide (PAO) significantly decreased expression of ER stress inducible proteins, glucose-regulated protein 94 (GRP94), and CCAAT/ enhancer-binding-protein-related gene (GADD153), which was induced by 2DG. In addition, we demonstrated that SOV and PAO noticeably restored the expression and glycosylation of COX-2 after treatment with 2DG. These results suggest that protein phosphorylation of tyrosine residues plays an important role in the regulation of expression and glycosylation during 2DG-induced ER stress in rabbit articular chondrocytes. [BMB reports 2012; 45(5): 317-322]

Aucubin prevents interleukin-1 beta induced inflammation and cartilage matrix degradation via inhibition of NF-κB signaling pathway in rat articular chondrocytes

“…c o m / l o c a t e / i n t i m p cytokine IL-1β is crucial for inflammatory process and articular tissue destruction in that it releases such inflammatory mediators as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) [5]. COX-2 is a rate-limiting enzyme for generation of prostaglandin E 2 (PGE 2 ) metabolites, an important mediator of inflammation and the anabolic/catabolic process linked to OA [6]. iNOS has been demonstrated to catalyze the oxidation to generate amounts of nitric oxide (NO) within the joint fluid of osteoarthritis chondrocytes, leading to cartilage destruction [7].…”

Sestrin-Mediated Inhibition of Stress-Induced Intervertebral Disc Degradation Through the Enhancement of Autophagy

“…Various intracellular and extracellular stimuli can affect the functions of the ER, leading to so-called ER stress. ER stress comprises stimuli that regulate a wide range of cellular responses including apoptosis, proliferation, inflammation, and differentiation in mammalian cells [35]. Many studies have shown that activation of the ER stress-induced apoptosis pathway contributes to various degenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and osteoarthritis [12, 13, 36].…”

“…Many studies have shown that activation of the ER stress-induced apoptosis pathway contributes to various degenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and osteoarthritis [12, 13, 36]. 2-DG is well known to induce ER stress by inhibiting glycolysis and N-glycosylation of proteins [35, 37]. In the present study, we used 2-DG to induce ER stress and observed its effects on cell apoptosis and the ECM degradation of human cultured NP cells.…”

Histone H2B Monoubiquitination Is Involved in Regulating the Dynamics of Microtubules during the Defense Response to Verticillium dahliae Toxins in Arabidopsis

“…Protein Tyr phosphorylation is controlled through the coordinated actions of PTKs and PTPs. However, typical Tyr kinases have not been predicted in any plants; only protein kinases with dual specificity have been reported in plant species (Sugiyama et al, 2008;Yu and Kim 2012;Nito et al, 2013). PTPs have been characterized from higher plants and are critical regulators of signal transduction in plant cells.…”