Effects of COX-2 overexpression on hippocampal neuronal damage induced by aluminum in rat

Abstract

Abstract: AIM: To study the relationship between COX-2 overexpression and hippocampal neuronal damage induced by aluminum. METHODS: Neonatal SD rats less than 24 h were used to establish the model of primary cultured hippocampal neuron treated aluminum overload(200 μmol/L). The primary cultured hippocampal neurons were transfected by adenovirus over expressing COX-2.The expression of COX-2 protein in hippocampal neurons was measured by Western Blot. The SOD and LDH activities and MDA contents were detected respectively. The cell viability was measured by MTT.The fluorescence detection was used to observe the change of neuronal pathomorphology. RESULTS: The transfection of adenovirus overexpressing COX-2 significantly increased the expression of COX-2 protein(P<0.01),without effects on neuronal pathomorphology, cell viability, the SOD activity and MDA content. However, it remarkably increased damage to neurons induced by aluminum overload.CONCLUSION: Acertain degree of COX-2 overexpression may not cause serious injury of neurons, but can increase the damage susceptibility of neurons undergoing aluminum overload.

Key words: COX-2 overexpression, Aluminum, Neuronal damage

CLC Number:

R965.2

WU Ke, XIE Ling-Yao, YANG Jun-qin. Effects of COX-2 overexpression on hippocampal neuronal damage induced by aluminum in rat[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(9): 967-971.

References

[1] Aïd S, Bosetti F.Targeting cyclooxygenases-1 and -2 in neuroinflammation: Therapeutic implications[J]. Biochimie,2011,93(1):46-51.
[2] Sang N, Yun Y, Yao GY,et al.SO2-induced neurotoxicity is mediated by cyclooxygenases-2-derived prostaglandin E2 and its downstream signaling pathway in rat hippocampal neurons[J]. Toxicol Sci,2011,124(2):400-413.
[3] Wu T, Wu H, Wang J,et al . Expression and cellular localization of cyclooxygenases and prostaglandin E synthases in the hemorrhagic brain[J]. J Neuroinflammation,2011,8:22.
[4] Ikeda-Matsuo Y, Hirayama Y, Ota A,et al . Microsomal prostaglandin E synthase-1 and cyclooxygenase-2 are both required for ischaemic excitotoxicity[J]. Br J Pharmacol,2010,159(5):1174-1186.
[5] Choi DW, Kolh JY.Quantitive determination of glutame mediated cortical neuronal injury in cell culture by lactate dehydrogenase efflux assay[J]. J Neurosci Methods, 1987, 5: 83-90.
[6] 江千里, 王健民, 温丽敏,等. 批量快速测定法测定标志基因为GFP 的重组病毒滴度[J]. 第二军医大学学报, 2002, 23(9): 4301-5301.
[7] Crapper DG, Krishnan S, Dakton AJ.Brain aluminum distribution in Alzheimer's diseaseand experimental neuro fibrillary degeneration[J]. Science, 1973, 180: 511-513.
[8] Mohamd EM, Ahmed HH, Estefan SF, et al . Windows into estradiol effects in Alzheimer's disease therapy[J]. Eur Rev Med Pharmacol Sci,2011,15(10):1131-1140.
[9] Kumar V, Bal A, Gill KD.Aluminium-induced oxidative DNA damage recognition and cell-cycle disruption in different regions of rat brain[J]. Toxicology,2009,264(3):137-144.
[10] 傅洪军, 董胜璋,林忠宁,等. JNK阻断剂CEP211004对铝诱导的大鼠皮层神经元凋亡的保护作用[J]. 中国药理学与毒理学杂志, 2003, 17(2): 106-110.
[11] Cuello AC, Ferretti MT, Leon WC,et al . Early-stage inflammation and experimental therapy in transgenic models of the Alzheimer-like amyloid pathology[J]. Neurodegener Dis,2010,7(1/2/3):96-98.
[12] Hoozemans JJ, Briickner MK,Rozemuller AJ, et a1. Cyelin D1 and cyclin E are colocalized with cyclooxygenase2 (COX-2) in pyramidal neurons in Alzheimer disease temporal cortex[J]. Neuropathol Exp Neurol, 2002, 61(8): 678-688.
[13] Strass KI, Barbe MF, Marshall RM, et al.Prolonged cyclooxygenase-2 induction in neurons and glia following traumatic brain injury in the rat[J]. J Neurotrauma, 2000, 17(8): 695-711.