Transcriptional and translational regulation of COX-2 expression by cadmium in C6 glioma cells

  • Authors:
    • Yu-Kyoung Park
    • Hua Hong
    • Byeong-Churl Jang
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  • Published online on: July 3, 2012     https://doi.org/10.3892/ijmm.2012.1052
  • Pages: 960-966
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Abstract

High exposure to cadmium is a risk factor for many neuronal diseases. Overexpression of cyclooxygenase (COX)-2 is linked to many neuroinflammatory and neoplastic diseases. We, herein, investigated the effect of cadmium on the expression of COX-2 in C6 rat glioma cells. Treatment with cadmium sulfate (cadmium) increased the expression of COX-2 mRNA. Remarkably, cadmium treatment further increased expression of not only the N-glycosylated COX-2 protein of 72 kDa but also the unglycosylated COX-2 of 66 kDa, as assessed by the unglycosylated COX-2 induced by tunicamycin or glucosamine, known inhibitors of COX-2 N-glycosylation. Of note, when translation was blocked in the presence of cycloheximide (CHX), levels of both N-glycosylated and unglycosylated COX-2 proteins induced by cadmium rapidly declined but the decline was prevented by MG132, a 26S proteasomal inhibitor. However, in the absence of CHX, cadmium induced and maintained expression of the unglycosylated COX-2 proteins. Pharmacological inhibition studies importantly demonstrated that the cadmium-mediated COX-2 transcriptional upregulation in C6 cells was not shown by exogenous glutathione (GSH) supplementation or treatment with inhibitors of extracellular signal-regulated protein kinase-1/2 (ERK-1/2), p38 MAPK and c-Jun N-terminal protein kinase-1/2 (JNK-1/2), respectively. Expression of COX-2 was not noted in C6 cells exposed to other heavy metals (cobalt or manganese). These results demonstrate that cadmium specifically induces expression of COX-2 through both transcriptional and co-translational (N-glycosylation) regulation in C6 cells in which the cadmium-induced COX-2 transcriptional upregulation is closely related to oxidative stress-dependent activation of the family of MAPKs and the cadmium-induced expression of both N-glycosylated and unglycosylated COX-2 proteins is proteasome- and translation-dependent.
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October 2012
Volume 30 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Park Y, Hong H and Jang B: Transcriptional and translational regulation of COX-2 expression by cadmium in C6 glioma cells. Int J Mol Med 30: 960-966, 2012
APA
Park, Y., Hong, H., & Jang, B. (2012). Transcriptional and translational regulation of COX-2 expression by cadmium in C6 glioma cells. International Journal of Molecular Medicine, 30, 960-966. https://doi.org/10.3892/ijmm.2012.1052
MLA
Park, Y., Hong, H., Jang, B."Transcriptional and translational regulation of COX-2 expression by cadmium in C6 glioma cells". International Journal of Molecular Medicine 30.4 (2012): 960-966.
Chicago
Park, Y., Hong, H., Jang, B."Transcriptional and translational regulation of COX-2 expression by cadmium in C6 glioma cells". International Journal of Molecular Medicine 30, no. 4 (2012): 960-966. https://doi.org/10.3892/ijmm.2012.1052