Environmental Analysis Health and Toxicology

The Korean Society of Environmental Health and Toxicology (환경독성보건학회)
권호 표지

Cadmium-induced COX-2 Expression in Cerebrovascular Endothelial Cells

카드뮴이 뇌혈관 내피세포에서의 $PGE^2$ 및 COX-2 발현에 미치는 영향

  • 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)
  • Published : 2006.09.01
Download PDF
⟨ Previous Next ⟩

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

References

  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 https://doi.org/10.1016/S0892-0362(96)00218-8
  2. Berglund M, Akesson A, Bjellerup P and Vahter M. Metalbone interactions. Toxicol. Lett. 2000; 15: 112-113:219-225
  3. 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 https://doi.org/10.1074/jbc.272.14.9086
  4. 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 https://doi.org/10.1136/oem.57.2.94
  5. 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 https://doi.org/10.1046/j.1471-4159.2000.0750614.x
  6. 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 https://doi.org/10.1074/jbc.M109145200
  7. 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 https://doi.org/10.1074/jbc.273.36.23183
  8. Hart RP, Rose CS and Hamer RM. Neuropsychological effects of occupational exposure to cadmium. J. Clin. Exp. Neuropsychol. 1989; 11: 933-943 https://doi.org/10.1080/01688638908400946
  9. Iadecola C and Alexander M. Cerebral ischemia and inflammation. Curr. Opin. Neurol. 2001; 14: 89-94 https://doi.org/10.1097/00019052-200102000-00014
  10. 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
  11. 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 https://doi.org/10.1016/j.bbrc.2004.05.218
  12. 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 https://doi.org/10.1016/S0006-291X(02)00824-0
  13. 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
  14. Minghetti L. Cyclooxygenase-2 (COX-2) in inflammatory and degenerative brain diseases. J. Neuropathol. Exp. Neurol. 2004; 63: 901-910 https://doi.org/10.1093/jnen/63.9.901
  15. 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 https://doi.org/10.1523/JNEUROSCI.17-08-02746.1997
  16. Okuda B, Iwamoto Y, Tachibana H and Sugita M. Parkinsonism after acute cadmium poisoning. Clin. Neurol. Neurosurg. 1997; 99: 263-265 https://doi.org/10.1016/S0303-8467(97)00090-5
  17. Pourahmad J and O′Brien PJ. A comparison of hepatocyte cytotoxic mechanisms for $Cu^{2+}$ and $Cd^{2+}$. Toxicology 2000; 143: 263-273 https://doi.org/10.1016/S0300-483X(99)00178-X
  18. 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 https://doi.org/10.1074/jbc.M406749200
  19. 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 https://doi.org/10.1016/S0378-4274(03)00237-6
  20. 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 https://doi.org/10.1016/j.cellsig.2003.08.006
  21. 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 https://doi.org/10.1007/s002040050610
  22. 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 https://doi.org/10.1016/j.toxlet.2006.04.007
  23. 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 https://doi.org/10.1177/096032719601500507
  24. 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
  25. Wyss-Coray T and Mucke L. Inflammation in neurodegenerative disease-a double-edged sword. Neuron 2002; 35: 419-432 https://doi.org/10.1016/S0896-6273(02)00794-8
  26. 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 https://doi.org/10.1002/jbt.10062
  27. 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 https://doi.org/10.1182/blood-2003-01-0049
  28. 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