Browse > Article

Cadmium-induced COX-2 Expression in Cerebrovascular Endothelial Cells  

Park Dong-Hyun (Department of Physiology, Ajou University School of Medicine)
Kim Young-Chae (Department of Physiology, Ajou University School of Medicine)
Moon Chang-Kiu (College of Pharmacy, Seoul National University)
Jung Yi-Sook (Department of Physiology, Ajou University School of Medicine)
Baik Eun-Joo (Department of Physiology, Ajou University School of Medicine)
Moon Chang-Hyun (Department of Physiology, Ajou University School of Medicine)
Lee Soo-Hwan (Department of Physiology, Ajou University School of Medicine)
Publication Information
Environmental Analysis Health and Toxicology / v.21, no.3, 2006 , pp. 275-282 More about this Journal
Abstract
In order to get insight into the mechanism of cadmium (Cd)-induced brain injury, we investigated the effects of Cd on the induction of COX-2 in bEnd.3 mouse brain endothelial cells. Cd induced COX-2 expression and $PGE_2$ release, which were attenuated by thiol-reducing antioxidant N-acetylcysteine (NAC) indicating oxidative components might contribute to these events. Indeed, Cd increased cellular reactive oxygen species (ROS) level and DNA binding activity of nuclear factor-kB (NF-kB), an oxidative stress sensitive transcription factor. Cd-induced $PGE_2$ production and COX-2 expression were significantly attenuated by Bay 11 7082, a specific inhibitor of NF-kB and by SB203580, a specific inhibitor of p38 mitogen activated protein kinase (MAPK). These data suggest that Cd induces COX-2 expression through activation of NF-kB and p38 MAPK, the oxidative stress-sensitive signaling molecules, in brain endothelial cells.
Keywords
cadmium; brain endothelial cell; cyclooxygenase-2; oxidative stress;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Andersson H, Petersson-Grawe K, Lindqvist E, Luthman J, Oskarsson A and Olson L. Low level cadmium exposure of lactating rats causes alterations in brain serotonin levels in the offspring. Neurotoxicol. Teratol. 1997; 19: 105-115   DOI   ScienceOn
2 Berglund M, Akesson A, Bjellerup P and Vahter M. Metalbone interactions. Toxicol. Lett. 2000; 15: 112-113:219-225
3 Elliott P, Arnold R, Cockings S, Eaton N, Jarup L, Jones J, Quinn M, Rosato M, Thornton I, Toledano M, Tristan E and Wakefield J. Risk of mortality, cancer incidence, and stroke in a population potentially exposed to cadmium. Occup. Environ. Med. 2000; 57(2): 94-97   DOI
4 Fang X, Moore AS, Nwankwo JO, Weintraub LN, Oberley WL, Snyder DG and Spector AA. Induction of cyclooxygenase-2 by overexpression of the human catalase gene in cerebral microvascular endothelial cells. J. Neurochem. 2000; 75(2): 614-623   DOI
5 Jeong EM, Moon CH, Kim CS, Lee SH, Baik E.J, Moon CK and Jung YS. Cadmium stimulates the expression of ICAM-1 via NF-B activation in cerebrovascular endothelial cells. Biochem. Biophys. Res. Commun. 2004; 320: 887-892   DOI   ScienceOn
6 Kim SJ, Im DS, Kim SH, Ryu JH, Hwang SG, Seong JK, Shun CH and Chun JS. Beta-catenin regulates expression of cyclooxygenase-2 in articular chondrocytes. Biochem. Biophys. Res Commun. 2002; 296(1): 221-226   DOI   ScienceOn
7 Minghetti L. Cyclooxygenase-2 (COX-2) in inflammatory and degenerative brain diseases. J. Neuropathol. Exp. Neurol. 2004; 63: 901-910   DOI
8 Nogawa S, Zhang F, Ross ME and Iadecola C. Cyclooxygenase- 2 gene expression in neuronscon-tributes to ischemic brain damage. J. Neurosci. 1997; 17: 2746-2755   DOI
9 Rockwell P, Martinez J, Papa L and Gomes E. Redox regulates COX-2 upregulation and cell death in the neuronal response to cadmium. Cell Signal. 2004; 16: 343-353   DOI   ScienceOn
10 Zhang F, Hackett NR, Lam G, Cheng J, Pergolizzi R, Luo L, Shmelkov SV, Edelberg J, Crystal RG and Rafii S. Green fluorescent protein selectively induces HSP70-mediated up-regulation of COX-2 expression in endothelial cells. Blood 2003; 102(6): 2115-2121   DOI   ScienceOn
11 Zimmerhackl LB, Momn F, Wiegele G and Brandis M. Cadmium is more toxic to LLC-PKl cells than to MDCK cells acting on the cadherine-catenin complex. Am. J. Physiology 1998; 275 (1 Pt 2): F143-154
12 Seok SM, Park DH, Kim YC, Moon CH, Jung YS, Baik EJ, Moon CK and Lee SH. COX-2 is associated with cadmium-induced ICAM-1 expression in cerebrovas-cular endothelial cells. Toxicol. Lett. 2006; 165: 212-220   DOI   ScienceOn
13 Hart RP, Rose CS and Hamer RM. Neuropsychological effects of occupational exposure to cadmium. J. Clin. Exp. Neuropsychol. 1989; 11: 933-943   DOI
14 Iadecola C and Alexander M. Cerebral ischemia and inflammation. Curr. Opin. Neurol. 2001; 14: 89-94   DOI   ScienceOn
15 Pourahmad J and O′Brien PJ. A comparison of hepatocyte cytotoxic mechanisms for $Cu^{2+}$ and $Cd^{2+}$. Toxicology 2000; 143: 263-273   DOI   ScienceOn
16 Wyss-Coray T and Mucke L. Inflammation in neurodegenerative disease-a double-edged sword. Neuron 2002; 35: 419-432   DOI   ScienceOn
17 Qanungo S, Wang M and Nieminen AL. N-Acetyl-Lcysteine enhances apoptosis through inhibition of nuclear $factor\;-{\kappa}B$ in hypoxic murine embryonic fibroblasts. J. Biol. Chem. 2004; 279(48): 50455-50464   DOI   ScienceOn
18 Romare A and Lundholm CE. Cadmium-induced calcium release and prostaglandin E2 production in neonatal mouse calvaria are dependent on COX-2 induction and protein kinase C activation. Arch. Toxicol. 1999; 73: 223-228   DOI
19 Stohs SJ, Bagchi D, Hassoun E and Bagchi M. Oxidative mechanisms in the toxicity of chromium and cadmium ions. J. Environ. Pathol. Toxicol. Oncol. 2000; 19: 201-213
20 Bush KT, Goldberg AL and Nigam SK. Proteaspme inhibition leads to a heat-shock response, induction of endoplasmic reticulum chaperones, and thermotolerance. J. Biol. Chem. 1997; 272(14): 9086-9092   DOI   ScienceOn
21 Laporte JD, Moore PE. Lahiri T, Schwartzman IN, Panettieri RA Jr and Shore SA. p38 MAP kinase regulates IL-1 beta responses in cultured airway smooth muscle cells. Am. J. Physiol. Lung Cell Mol. Physiol. 2000; 279(5): L932-941
22 Figueiredo-Pereira ME, Li Z, Jasen M and Rockwell P. N-acetylcysteine and celecoxib lessen cadmium cytotoxicity which is associated with cyclooxygenase-2 upregulation in mouse neuronal cells. J. Biol. Chem. 2002; 277: 25283-25289   DOI   ScienceOn
23 Iadecola C, Niwa K, Nogawa S, Zhao X, Nagayama M, Araki E, Morham S and Ross ME. Reduced susceptibility to ischemic brain injury and NMDA-mediated neurotoxicity in cyclooxygense deficient mice. Proc. Natl. Acad. Sci. USA. 2001; 98: 1294-1299
24 Xu J, Maki D and Stapleton SR. Mediation of cadmiuminduced oxidative damage and glucose-6-phosphate dehydrogenase expression through glutathione depletion. J. Biochem. Mol. Toxicol. 2003; 17: 67-75   DOI   ScienceOn
25 Gallois C, Habib A, Tao J, Moulin S, Maclouf J, Mallat A and Lotersztajn S. Role of $NF-{\kappa}B$ in the antiproliferative effect of endothelin-1 and tumor nectosis $factor-{\alpha}$ in human hepatic stellate cells. J. Biol. Chem. 1998; 273(36): 23183-23190   DOI   ScienceOn
26 Shukla A, Shukla GS and Srimal RC. Cadmium-induced alterations in blood-brain barrier permeability and its possible correlation with decreased microvessel antioxidant potential in rat. Hum. Exp. Toxicol. 1996; 15: 400-405   DOI
27 Okuda B, Iwamoto Y, Tachibana H and Sugita M. Parkinsonism after acute cadmium poisoning. Clin. Neurol. Neurosurg. 1997; 99: 263-265   DOI   ScienceOn
28 Ramirez DC and Gimenez MS. Induction of redox changes, inducible nitric oxide synthase and cyclooxygenase-2 by chronic cadmium exposure in mouse peritoneal macrophages. Toxicol. Lett. 2003; 145: 121-132   DOI   ScienceOn