title: Unilateral upregulation of cyclooxygenase-2 following cerebral, cortical photothrombosis in the rat: suppression by MK-801 and co-distribution with enzymes involved in the oxidative stress cascade.
abstract: Cyclooxygenase-2 (COX-2) is an essential enzyme for prostaglandin synthesis from arachidonic acid, during which considerable amounts of superoxide are produced. During pathological conditions, superoxide and nitric oxide (NO) rapidly form peroxynitrite, a potent cytotoxin, causing symptoms referred to as oxidative stress response. Superoxide is controlled by enzymes such as manganese- or copper-zinc-dependent superoxide dismutase (Mn-SOD, CuZn-SOD), glutathione peroxidase (GPx) and antioxidants derived from heme oxygenase (HO) activity such as biliverdin and bilirubin. NO derives from 3 NO-synthases (NOS I-III) from which the calcium-dependent NOS-I and III are activated rapidly due to hyperexcitation. We studied the induction of COX-2 by immunohistochemistry at days 1, 2 and 5 following cortical photothrombosis in normal and MK-801 treated rats. The results showed a weak constitutive, neuronal expression of COX-2 in cortex and amygdala. Layers II+III contained considerably more COX-2 than infragranular layers. One and 2 days following injury COX-2 was highly upregulated in the supragranular layers of the whole injured hemisphere compared with sham-operated animals and compared to the contralateral unlesioned hemisphere, whereas at day 5 COX-2 levels had returned to baseline. MK-801 treatment caused a reduction in COX-2 upregulation at day one and by day 2 no significant differences between injured and contralateral hemisphere were measurable. COX-2 positive neurons were found in close association with NOS-I containing neurons and their fibers but were not colocalized. In addition, codistribution of COX-2 was found with HO-1, CuZn-SOD and GPx containing cells, whereas COX-2 was colocalized with HO-2 and/or MnSOD in cortical neurons.
authors: C.&O. Vogt Institute of Brain Research, Building 22.03.05, Heinrich-Heine-University, Moorenstrasse. 5, D-40225 Düsseldorf, Germany. hjb@hirn.uni-duesseldorf.de
authors: H J
authors: HJ
authors: Bidmon
authors: E
authors: E
authors: Oermann
authors: K
authors: K
authors: Schiene
authors: M
authors: M
authors: Schmitt
authors: K
authors: K
authors: Kato
authors: K
authors: K
authors: Asayama
authors: O W
authors: OW
authors: Witte
authors: K
authors: K
authors: Zilles
mesh_terms: D000679:Amygdala / Q000201:enzymology; D000818:Animals; D051546:Cyclooxygenase 2; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D020767:Intracranial Thrombosis / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D018691:Excitatory Amino Acid Antagonists; D007527:Isoenzymes; D009569:Nitric Oxide; D016291:Dizocilpine Maleate; D005979:Glutathione Peroxidase; D006419:Heme Oxygenase (Decyclizing); D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D013482:Superoxide Dismutase