Oxidation and cytotoxicity of 6-OHDA are mediated by reactive intermediates of COX-2 overexpressed in PC12 cells.


:Parkinson's disease is characterized by a progressive loss of dopaminergic neurons, likely associated with dysregulation of oxidation of catechols, such as dopamine (DA) and 6-hydroxydopamine (6-OHDA), and resulting in oxidative stress. The involvement of cyclooxygenase-2 (COX-2) in pathogenesis of Parkinson's disease has been suggested. However, specific COX-2 triggered mechanisms participating in catalysis of DA oxidation and enhanced catechol-induced cytotoxicity remain poorly characterized. Here, we demonstrate that in a model biochemical system, recombinant heme-reconstituted COX-2 induced oxidation of 6-OHDA in the course of its peroxidase (H(2)O(2)-dependent) and cyclooxygenase (arachidonic acid (AA)-dependent) catalytic half-cycles. Similarly, COX-2 was able to stimulate 6-OHDA oxidation during its peroxidase- and cyclooxygenase half-cycles and caused oxidative stress in homogenates of PC12 cells stably overexpressing the enzyme (but not in mock-transfected cells). In addition, the increased levels of COX-2 were associated with enhanced cytotoxicity of 6-OHDA in stably transfected PC12 cells. Finally, co-oxidation of 6-OHDA by COX-2 triggered production of superoxide radicals critical for both propagation of 6-OHDA oxidation and induction of oxidative stress in COX-2 overexpressing cells. Thus, we conclude that both peroxidase and cyclooxygenase half-cycles of COX-2-catalyzed reactions are essential for COX-2-dependent activation of 6-OHDA oxidation, oxygen radical production, oxidative stress, and cytotoxicity.


Brain Res


Brain research


Tyurina YY,Kapralov AA,Jiang J,Borisenko GG,Potapovich AI,Sorokin A,Kochanek PM,Graham SH,Schor NF,Kagan VE




Has Abstract


2006-06-06 00:00:00














  • Vasopressin and glucoprivic-feeding behavior: a new perspective on an 'old' peptide.

    abstract::The feeding responses induced by systemic administration of 2-deoxy-D-glucose (2-DG) and paraventricular hypothalamic injection of norepinephrine were assessed in Brattleboro rats deficient in vasopressin (VP). Controlling for the non-specific complications of diabetes insipidus, it was found that Brattleboro rats hav...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Aravich PF,Sladek CD

    更新日期:1986-10-22 00:00:00

  • Organization of efferent projections of the subthalamic nucleus in the squirrel monkey as revealed by retrograde labeling methods.

    abstract::The cellular origin and degree of collateralization of the subthalamostriatal, subthalamonigral and subthalamopallidal projections in the squirrel monkey (Saimiri sciureus) were studied using lectin-conjugated horseradish peroxidase (WGA-HRP), Nuclear yellow (NY) and Fast blue (FB) as retrograde tracers. In a first ex...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Parent A,Smith Y

    更新日期:1987-12-15 00:00:00

  • Effects of monocular enucleation at different stages of development on the uncrossed retinocollicular projection in the opossum.

    abstract::Pouch young opossums aged from 5 to 34 days underwent unilateral eye enucleation and the projection from the remaining eye to the superior colliculus (SC) was explored at maturity by anatomical and physiological methods. The results were compared to data from normal or adult enucleated animals. Analysis of the experim...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Méndez-Otero R,Rocha-Miranda CE,Carvalho-Dias E

    更新日期:1986-06-01 00:00:00

  • Neural evidence of a role for spatial response selection in the learning of spatial sequences.

    abstract::Despite over 20 years of behavioral research, considerable disagreement remains regarding the locus of the cognitive mechanisms (e.g., stimulus encoding, response selection or response production) responsible for the acquisition and expression of learned sequences. Functional neuroimaging may prove invaluable for reso...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Schwarb H,Schumacher EH

    更新日期:2009-01-09 00:00:00

  • ‬The expression of purinergic P2X4 and P2X7 receptors in selected mesolimbic structures during morphine withdrawal in rats.

    abstract::Morphine is one of the most potent analgesics used in medicine and it's long-term use is associated with the risk of the state of dependence. The cessation of chronic morphine administration leads to withdrawal signs which are associated with neurotransmitter dysregulations within mesolimbic system. Adenosine 5'-triph...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Metryka E,Gutowska I,Kupnicka P,Tarnowski M,Tkacz M,Listos J,Talarek S,Barczak K,Chlubek D,Baranowska-Bosiacka I

    更新日期:2019-09-15 00:00:00

  • A glial blood-brain barrier in elasmobranchs.

    abstract::The blood-brain interface in elasmobranchs was examined using physiological and anatomical techniques. Electrolyte analyses of plasma and cerebrospinal fluid (CSF) in control fish and in fish with elevated plasma cation concentration (Ca, Mg or K) demonstrated homeostasis of CSF calcium and magnesium concentrations in...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Bundgaard M,Cserr H

    更新日期:1981-12-07 00:00:00

  • Region-specific alterations in glutamate receptor expression and subcellular distribution following extinction of cocaine self-administration.

    abstract::A role for glutamatergic signaling in the nucleus accumbens (NA) in both the expression and extinction of cocaine seeking has been suggested. The effects of extinction following cocaine self-administration on the expression and synaptosomal distribution of GluR1 and NMDAR1 glutamate receptor subunits in the NA shell a...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Ghasemzadeh MB,Vasudevan P,Mueller CR,Seubert C,Mantsch JR

    更新日期:2009-04-24 00:00:00

  • Suprachiasmatic nucleus ablation abolishes circadian rhythms in rat brain neurotransmitter receptors.

    abstract::The effect of suprachiasmatic nucleus (SCN) ablation on rhythms in brain neurotransmitter receptors was studied. In control animals, the rhythms in the number of alpha-adrenergic and benzodiazepine receptors were circadian, whereas the rhythms in beta-adrenergic and acetylcholine receptors were ultradian. SCN ablation...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Kafka MS,Marangos PJ,Moore RY

    更新日期:1985-02-18 00:00:00

  • Unmyelinated primary afferents from adjacent spinal nerves intermingle in the spinal dorsal horn: a possible mechanism contributing to neuropathic pain.

    abstract::Peripheral nerve injury in animals can cause neuropathic pain often expressed in the form of hyperalgesia and allodynia. Spinal nerve ligation, in which the fifth and sixth lumbar (L5 and L6) or only the L5 spinal nerve is ligated and cut, is a model commonly used to produce neuropathic pain. The purpose of the presen...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Shehab SA,Al-Marashda K,Al-Zahmi A,Abdul-Kareem A,Al-Sultan MA

    更新日期:2008-05-07 00:00:00

  • Multiple brain systems generating the rat auditory evoked potential. II. Dissociation of auditory cortex and non-lemniscal generator systems.

    abstract::This study addressed the issue of multiple parallel auditory processing systems and their relationship to the skull-recorded auditory evoked potentials (AEPs) in the unanesthetized, unrestrained rat. In the preceding paper (Brain Res., 602 (1993) 240-250) it has been shown that auditory cortex activity does not contri...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Simpson GV,Knight RT

    更新日期:1993-02-05 00:00:00

  • Method of administration determines the effect of naloxone on pain.

    abstract::The opiate antagonist, naloxone, produces dose-dependent biphasic changes in clinical pain. The mechanism of the analgesia produced by low dose naloxone is unknown. To study the analgesic effect of naloxone, we have used a programmable infusion pump, which eliminates placebo-induced endorphin-mediated analgesia, to ad...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Levine JD,Gordon NC

    更新日期:1986-02-19 00:00:00

  • Regulation of AQP4 protein expression in rat brain astrocytes: role of P2X7 receptor activation.

    abstract::ATP has been recognized as an important extracellular signaling molecule and P2X receptors are membrane ion channels activated by the binding of extracellular ATP. Since both AQP4 and P2X7 receptor (P2X7R) are known to be present in astrocytes, we examined whether P2X7R activation plays a role in the regulation of AQP...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Lee M,Lee SJ,Choi HJ,Jung YW,Frøkiaer J,Nielsen S,Kwon TH

    更新日期:2008-02-21 00:00:00

  • Neural control of the daily rhythm of sexual behavior in the male golden hamster.

    abstract::Circadian and neural mechanisms important for the organization of reproductive behavior in the male golden hamster were examined. The sexual behavior of male hamsters exhibits diel variations; males are quicker to initiate copulation and to ejaculate in the dark phase than in the light phase of a daily light-dark cycl...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Eskes GA

    更新日期:1984-02-13 00:00:00

  • Long-term administration of estrogen or tamoxifen to ovariectomized rats affords neuroprotection to hippocampal neurons by modulating the expression of Bcl-2 and Bax.

    abstract::Recently we reported that chronic treatment with 17beta-estradiol (E2) or tamoxifen (TAM) regulates the ovariectomy-induced downregulation of the key molecules linked to hippocampal synaptic plasticity and signal transduction pathway. We now report modulation of the antiapoptotic (Bcl-2) and proapoptotic (Bax) protein...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Sharma K,Mehra RD

    更新日期:2008-04-14 00:00:00

  • The dopamine D-1 receptor antagonist SCH 23390 injected into the dorsolateral bed nucleus of the stria terminalis decreased cocaine reinforcement in the rat.

    abstract::The effects of bilateral intracranial injections of the D-1 dopamine receptor antagonist SCH 23390 HCl (0, 0.8, 1.6, 3.2, and 6.4 microgram total bilateral dose) administered into the dorsolateral bed nucleus of the stria terminalis (dlBNST) immediately prior to a 3 h intravenous cocaine self-administration session we...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Epping-Jordan MP,Markou A,Koob GF

    更新日期:1998-02-16 00:00:00

  • Effects of enkephalin and 5-hydroxytryptamine on solitary tract neurones involved in respiration and respiratory reflexes.

    abstract::Both enkephalin and 5-hydroxytryptamine (5-HT) have been implicated in neural mechanisms underlying the central control of respiration. In view of the role of the nuclei tractus solitarii (NTS) in respiratory regulation, we carried out a study in artificially ventilated, chloralose-anaesthetized cats of the effects of...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Sessle BJ,Henry JL

    更新日期:1985-02-18 00:00:00

  • Response of rat brain to calcitonin alteration.

    abstract::Endogenous calcitonin was altered in rats by thyroparathyroidectomy, followed by supplementation with thyroxine and calcium. As a result, a reduction in the content of 5-hydroxytryptamine in the brain together with an increase in the concentration of tryptophan in the plasma were observed. The changes were accompanied...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Nakhla AM,Latif A

    更新日期:1982-04-29 00:00:00

  • Ketogenic diet prevents clusterin accumulation induced by kainic acid in the hippocampus of male ICR mice.

    abstract::We investigated the effect of ketogenic diet (KD) on clusterin accumulation in the kainic acid (KA)-induced seizure model. Two days after KA administration, strong clusterin-like immunoreactivity (IR) was detected in the hippocampus in the normal diet (ND)-fed mice. But in the KD-fed mice, few clusterin-like IR was de...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Noh HS,Kim DW,Kang SS,Cho GJ,Choi WS

    更新日期:2005-04-25 00:00:00

  • Evidence for the existence of cAMP-dependent protein kinase phosphorylation system associated with specific phosphoproteins in stable microtubules from rat cerebral cortex.

    abstract::Cyclic AMP is a second messenger by which different extracellular signals are transduced into biological responses. Within the cell, most of the effects of cAMP are mediated through the cAMP protein kinase which appears to be localized in specific compartments of the cell near to their substrate proteins. In the prese...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Perez J,Tinelli D,Cagnoli C,Pecin P,Brunello N,Racagni G

    更新日期:1993-01-29 00:00:00

  • Modulation of brown adipose tissue-mediated thermogenesis by lesions to the nucleus tractus solitarius in the rat.

    abstract::Given that relatively little is known regarding the central control of brown adipose tissue (BAT)-mediated thermogenesis the present study assessed whether the direct pharmacological stimulation of beta- or alpha-adrenergic receptors located on the brown adipocytes would result in a typical thermogenic response follow...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Fyda DM,Cooper KE,Veale WL

    更新日期:1991-04-19 00:00:00

  • Vocalization-related stapedius muscle activity in different age chickens (Gallus gallus), and its role in vocal development.

    abstract::The stapedius muscle activity associated with vocalization was analyzed in young and adult roosters. Our results show that remarkable differences in the behavior of vocalization-related stapedius muscle activity exist between these two ages. Unlike young roosters, electrical stimulation in the midbrain of adult cocks ...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Grassi S,Ottaviani F,Bambagioni D

    更新日期:1990-10-08 00:00:00

  • Vicia villosa lectin-positive neurones in human cerebral cortex. Loss in Alzheimer-type dementia.

    abstract::Frontal and temporal sections of 4 normal human brains and 3 brains from patients with a diagnosis of Alzheimer-type dementia (ATD) were stained with Vicia villosa lectin conjugated to biotin to localize glycoproteins containing terminal N-acetylgalactosamine. These lectin binding sites were localized at the surface o...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Kobayashi K,Emson PC,Mountjoy CQ

    更新日期:1989-09-25 00:00:00

  • Sex-related hemispheric lateralization of electrical potentials evoked by arousing negative stimuli.

    abstract::Recent studies suggest that both sex and cerebral hemisphere influence brain mechanisms associated with emotional memory. Here we used evoked potentials to examine the influence of sex and hemisphere on brain responses to emotional stimuli. Given that the P300 component of the event-related brain potential (ERP) is co...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Gasbarri A,Arnone B,Pompili A,Pacitti F,Pacitti C,Cahill L

    更新日期:2007-03-23 00:00:00

  • Characterization of electrophysiological properties of intracellularly recorded neurons in the neocortex of awake cats: a comparison of the response to injected current in spike overshoot and undershoot neurons.

    abstract::Intracellular recordings were obtained from 212 neurons of the coronal pericruciate cortex of 7 awake, untrained cats. Glass microelectrodes, filled with K+ citrate alone or K+ citrate with either cyclic GMP or 5'-GMP were used for recording and for injecting steady depolarizing and hyperpolarizing currents intracellu...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Woody CD,Gruen E

    更新日期:1978-12-15 00:00:00

  • Central angiotensin III-induced dipsogenicity in rats and gerbils.

    abstract::Previous findings from our laboratory demonstrated [125I]angiotensin II (AII) binding to plasma membranes from rat but not gerbil circumventricular organs (CVOs), the presumed location of brain receptors for angiotensin-induced dipsogenicity. Since members of both species drink to intracranially applied AII, a degrada...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Wright JW,Morseth S,Mana MJ,LaCrosse E,Petersen EP,Harding JW

    更新日期:1984-03-12 00:00:00

  • Feeding induced by microinjections of NMDA and AMPA-kainate receptor antagonists into ventral striatal and ventral pallidal areas of the pigeon.

    abstract::The participation of glutamatergic circuits of the ventral basal ganglia in feeding-related regulatory mechanisms has been extensively indicated in primate and rodent species. In avian species, it has been shown that ICV injections of MK-801 or of CNQX increase food intake and reduce the latency of feeding initiation ...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Da Silva AA,Marino-Neto J,Paschoalini MA

    更新日期:2003-03-14 00:00:00

  • Expression of c-fos-like immunoreactivity in the feline brainstem in response to isometric muscle contraction and baroreceptor reflex changes in arterial pressure.

    abstract::This study compared whether activation of muscle ergoreceptor afferents caused by isometric muscle contraction, activation of baroreceptor afferents induced by i.v. infusion of phenylephrine, or baroreceptor afferent inactivation, caused by carotid artery occlusion, elicit similar patterns of c-Fos induction in brains...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Williams CA,Loyd SD,Hampton TA,Hoover DB

    更新日期:2000-01-10 00:00:00

  • Altered expression of preproenkephalin and prodynorphin mRNA in a genetic model of paroxysmal dystonia.

    abstract::The dtsz mutant hamster represents a model of primary paroxysmal dystonia, in which dystonic episodes occur in response to stress. Previous examinations demonstrated striatal dysfunctions in dtsz hamsters. In the present study, in situ hybridization was used to examine preproenkephalin and prodynorphin expression as p...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Nobrega JN,Parkes JH,Wong P,Raymond R,Richter A

    更新日期:2004-07-23 00:00:00

  • Selective stimulation of kainate but not quisqualate or NMDA receptors in substantia nigra evokes limbic motor seizures.

    abstract::Bilateral microinjection of kainic acid (30-117 pmol) into the substantia nigra induced convulsive seizures resembling those elicited from limbic system structures. The convulsive seizures, which consisted of facial and forelimb clonus with rearing and falling, developed after a latency of more than 30 min and were pr...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Maggio R,Liminga U,Gale K

    更新日期:1990-10-01 00:00:00

  • Recovery of consummatory feeding behavior after bilateral lesions of the cerebral-buccal connectives in Aplysia californica.

    abstract::In the sea hare, Aplysia californica, consummatory feeding behavior is selectively abolished by bilateral crushes of the cerebral-buccal connectives and recovers by postlesion day 13. Recovered biting responses are initially weak and increase in magnitude gradually with time. The lesions do not affect appetitive feedi...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Scott ML,Kirk MD

    更新日期:1992-07-10 00:00:00