Glutathione depletion resulting in selective mitochondrial complex I inhibition in dopaminergic cells is via an NO-mediated pathway not involving peroxynitrite: implications for Parkinson's disease.

Abstract:

:An early biochemical change in the Parkinsonian substantia nigra (SN) is reduction in total glutathione (GSH + GSSG) levels in affected dopaminergic neurons prior to depletion in mitochondrial complex I activity, dopamine loss, and cell death. We have demonstrated using dopaminergic PC12 cell lines genetically engineered to inducibly down-regulate glutathione synthesis that total glutathione depletion in these cells results in selective complex I inhibition via a reversible thiol oxidation event. Here, we demonstrate that inhibition of complex I may occur either by direct nitric oxide (NO) but not peroxinitrite-mediated inhibition of complex I or through H2O2-mediated inhibition of the tricarboxylic acid (TCA) cycle enzyme alpha-ketoglutarate dehydrogenase (KGDH) which supplies NADH as substrate to the complex; activity of both enzymes are reduced in PD. While glutathione depletion causes a reduction in spare KGDH enzymatic capacity, it produces a complete collapse of complex I reserves and significant effects on mitochondrial function. Our data suggest that NO is likely the primary agent involved in preferential complex I inhibition following acute glutathione depletion in dopaminergic cells. This may have major implications in terms of understanding mechanisms of dopamine cell death associated with PD especially as they relate to complex I inhibition.

journal_name

J Neurochem

authors

Hsu M,Srinivas B,Kumar J,Subramanian R,Andersen J

doi

10.1111/j.1471-4159.2004.02929.x

keywords:

subject

Has Abstract

pub_date

2005-03-01 00:00:00

pages

1091-103

issue

5

eissn

0022-3042

issn

1471-4159

pii

JNC2929

journal_volume

92

pub_type

杂志文章
  • Highly sensitive assay for dopamine-beta-hydroxylase activity in human cerebrospinal fluid by high performance liquid chromatography-electrochemical detection: properties of the enzyme.

    abstract::This paper describes a new, sensitive assay for dopamine-beta-hydroxylase (DBH) activity in human cerebrospinal fluid (CSF), serum and brain tissues by high performance liquid chromatography (HPLC) with electrochemical detection (ED). Dopamine (DA) was used as a substrate and was incubated under optimal conditions. No...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1981.tb00454.x

    authors: Matsui H,Kato T,Yamamoto C,Fujita K,Nagatsu T

    更新日期:1981-08-01 00:00:00

  • Myt1 family recruits histone deacetylase to regulate neural transcription.

    abstract::The myelin transcription factor 1 (Myt1) gene family is comprised of three zinc finger genes [Myt1, Myt1L (Myt1-Like) and NZF3] of the structurally unique CCHHC class that are expressed predominantly in the developing CNS. To understand the mechanism by which this family regulates neural differentiation, we searched f...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2005.03131.x

    authors: Romm E,Nielsen JA,Kim JG,Hudson LD

    更新日期:2005-06-01 00:00:00

  • Regulation of transmitter gamma-aminobutyric acid (GABA) synthesis and metabolism illustrated by the effect of gamma-vinyl GABA and hypoglycemia.

    abstract::The effect of different treatments on amino acid levels in neostriatum was studied to throw some light on the synthesis and metabolism of gamma-aminobutyric acid (GABA). Irreversible inhibition of GABA transaminase by microinjection of gamma-vinyl GABA (GVG) led to a decrease in aspartate, glutamate, and glutamine lev...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1988.tb10586.x

    authors: Paulsen RE,Fonnum F

    更新日期:1988-04-01 00:00:00

  • Selective linkage of mitochondrial enzymes to intracellular calcium stores differs between human-induced pluripotent stem cells, neural stem cells, and neurons.

    abstract::Mitochondria and releasable endoplasmic reticulum (ER) calcium modulate neuronal calcium signaling, and both change in Alzheimer's disease (AD). The releasable calcium stores in the ER are exaggerated in fibroblasts from AD patients and in multiple models of AD. The activity of the alpha-ketoglutarate dehydrogenase co...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/jnc.15160

    authors: Chen H,Cross AC,Thakkar A,Xu H,Li A,Paull D,Noggle SA,Kruger L,Denton TT,Gibson GE

    更新日期:2020-08-31 00:00:00

  • Injury-induced "switch" from GTP-regulated to novel GTP-independent isoform of tissue transglutaminase in the rat spinal cord.

    abstract::We recently found that alternative transcripts of tissue transglutaminase (tTG or TG2) were present in hippocampal brain regions of Alzheimer's disease (AD), but not in control, non-demented, age-matched brains. Since antecedent non-severe trauma has been implicated in AD and other neurodegenerative diseases, such as ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.2002.00850.x

    authors: Festoff BW,SantaCruz K,Arnold PM,Sebastian CT,Davies PJ,Citron BA

    更新日期:2002-05-01 00:00:00

  • Characterization and developmental expression of lactotriosylceramide:galactosyltransferase for the synthesis of neolactotetraosylceramide in the nervous system.

    abstract::Neolactoglycolipids are derived from neolactotetraosylceramide (nLcOse4Cer). They are found during the embryonic and neonatal developmental periods in the rat cerebral cortex and disappear shortly after birth. These glycolipids are, however, abundant in the adult cerebellum. Lactotriosylceramide (LcOse3Cer):galactosyl...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1994.62010307.x

    authors: Chou DK,Jungalwala FB

    更新日期:1994-01-01 00:00:00

  • Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain.

    abstract::Converging lines of evidence implicate the beta-amyloid peptide (Ass) as causative in Alzheimer's disease. We describe a novel class of compounds that reduce A beta production by functionally inhibiting gamma-secretase, the activity responsible for the carboxy-terminal cleavage required for A beta production. These mo...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.2001.00012.x

    authors: Dovey HF,John V,Anderson JP,Chen LZ,de Saint Andrieu P,Fang LY,Freedman SB,Folmer B,Goldbach E,Holsztynska EJ,Hu KL,Johnson-Wood KL,Kennedy SL,Kholodenko D,Knops JE,Latimer LH,Lee M,Liao Z,Lieberburg IM,Motter RN,

    更新日期:2001-01-01 00:00:00

  • Hydrophobic protein that copurifies with human brain acetylcholinesterase: amino acid sequence, genomic organization, and chromosomal localization.

    abstract::The mechanism of attachment of acetylcholinesterase (AChE) to neuronal membranes in interneuronal synapses is poorly understood. We have isolated, sequenced, and cloned a hydrophobic protein that copurifies with AChE from human caudate nucleus and that we propose forms a part of a complex of membrane proteins attached...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.2000.0742146.x

    authors: Navaratnam DS,Fernando FS,Priddle JD,Giles K,Clegg SM,Pappin DJ,Craig I,Smith AD

    更新日期:2000-05-01 00:00:00

  • Syntaxin 1B regulates synaptic GABA release and extracellular GABA concentration, and is associated with temperature-dependent seizures.

    abstract::De novo heterozygous mutations in the STX1B gene, encoding syntaxin 1B, cause a familial, fever-associated epilepsy syndrome. Syntaxin 1B is an essential component of the pre-synaptic neurotransmitter release machinery as a soluble N-ethylmaleimide-sensitive factor attachment protein receptor protein that regulates th...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/jnc.15159

    authors: Mishima T,Fujiwara T,Kofuji T,Saito A,Terao Y,Akagawa K

    更新日期:2020-08-28 00:00:00

  • Role of external and internal calcium on heterocarrier-mediated transmitter release.

    abstract::Release-regulating heterocarriers exist on brain nerve endings. We have investigated in this study the mechanisms involved in the neurotransmitter release evoked by GABA heterocarrier activation. GABA increased the basal release of [3H]acetylcholine and [3H]noradrenaline from rat hippocampal synaptosomes and of [3H]do...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1996.66041468.x

    authors: Fassio A,Bonanno G,Fontana G,Usai C,Marchi M,Raiteri M

    更新日期:1996-04-01 00:00:00

  • Early stress and chronic methylphenidate cross-sensitize dopaminergic responses in the adolescent medial prefrontal cortex and nucleus accumbens.

    abstract::Methylphenidate (MP) is widely used to treat attention deficit/hyperactivity disorder in children. However, basic research has been mainly focused on MP treatment in adult, behaviorally normal rodents. Here we analyzed MP-evoked changes of dopamine (DA) release in the limbic system of juvenile rodents with hyperactive...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2007.04927.x

    authors: Jezierski G,Zehle S,Bock J,Braun K,Gruss M

    更新日期:2007-12-01 00:00:00

  • Activation of Rho GTPases by synaptic transmission in the hippocampus.

    abstract::Ras-related GTPases of the Rho family, such as RhoA and RhoB, are well-characterised mediators of morphological change in peripheral tissues via their effects on the actin cytoskeleton. We tested the hypothesis that Rho family GTPases are involved in synaptic transmission in the CA1 region of the hippocampus. We show ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.2003.02102.x

    authors: O'Kane EM,Stone TW,Morris BJ

    更新日期:2003-12-01 00:00:00

  • The effect of Cyclin-dependent kinase 5 on voltage-dependent calcium channels in PC12 cells varies according to channel type and cell differentiation state.

    abstract::Cyclin-dependent kinase 5 (Cdk5) is a Ser/Thr kinase that plays an important role in the release of neurotransmitter from pre-synaptic terminals triggered by Ca(2+) influx into the pre-synaptic cytoplasm through voltage-dependent Ca(2+) channels (VDCCs). It is reported that Cdk5 regulates L-, P/Q-, or N-type VDCC, but...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/jnc.12746

    authors: Furusawa K,Asada A,Saito T,Hisanaga S

    更新日期:2014-08-01 00:00:00

  • Effect of unilateral perinatal hypoxic-ischemic brain injury in the rat on dopamine D1 and D2 receptors and uptake sites: a quantitative autoradiographic study.

    abstract::The effect of a unilateral perinatal hypoxic-ischemic brain injury on dopamine D1 and D2 receptors and uptake sites was investigated in rats by using in vitro quantitative binding autoradiography, 2-3 weeks after the insult. We observed significant decreases in the Bmax and KD for [3H]SCH 23390-labeled D1 and in the B...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1991.tb06409.x

    authors: Przedborski S,Kostic V,Jackson-Lewis V,Cadet JL,Burke RE

    更新日期:1991-12-01 00:00:00

  • Arachidonic acid increases choline acetyltransferase activity in spinal cord neurons through a protein kinase C-mediated mechanism.

    abstract::Arachidonic acid (AA) plays an important role as a signaling factor in the CNS. Therefore, exposure to AA may affect cholinergic neurons in the spinal cord. To test this hypothesis, mRNA expression and activity of choline acetyltransferase (ChAT) was measured in cultured spinal cord neurons treated with increasing con...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2004.02535.x

    authors: Chalimoniuk M,King-Pospisil K,Pedersen WA,Malecki A,Wylegala E,Mattson MP,Hennig B,Toborek M

    更新日期:2004-08-01 00:00:00

  • CDK5 protects from caspase-induced Ataxin-3 cleavage and neurodegeneration.

    abstract::Spinocerebellar ataxia type 3 (SCA3) is one of at least nine inherited neurodegenerative diseases caused by an expansion of a polyglutamine tract within corresponding disease-specific proteins. In case of SCA3, mutation of Ataxin-3 results in aggregation of misfolded protein, formation of intranuclear as well as cytos...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/jnc.12684

    authors: Liman J,Deeg S,Voigt A,Voßfeldt H,Dohm CP,Karch A,Weishaupt J,Schulz JB,Bähr M,Kermer P

    更新日期:2014-06-01 00:00:00

  • A monoclonal antibody raised against plasma membrane of cholinergic nerve terminals of the Torpedo inhibits choline acetyltransferase activity and acetylcholine release.

    abstract::Monoclonal antibodies were raised against the synaptosomal plasma membranes (SPMs) purified from the electric organ of the Torpedo. One antibody that reacts preferentially with SPMs rather than with other membrane fractions isolated from this tissue was previously found to inhibit hydrophilic and amphiphilic choline-O...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1989.tb08533.x

    authors: Eder-Colli L,Briand PA,Pellegrinelli N,Dunant Y

    更新日期:1989-11-01 00:00:00

  • Manganese exposure is cytotoxic and alters dopaminergic and GABAergic neurons within the basal ganglia.

    abstract::Manganese is an essential nutrient, integral to proper metabolism of amino acids, proteins and lipids. Excessive environmental exposure to manganese can produce extrapyramidal symptoms similar to those observed in Parkinson's disease (PD). We used in vivo and in vitro models to examine cellular and circuitry alteratio...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2009.06145.x

    authors: Stanwood GD,Leitch DB,Savchenko V,Wu J,Fitsanakis VA,Anderson DJ,Stankowski JN,Aschner M,McLaughlin B

    更新日期:2009-07-01 00:00:00

  • Iron trafficking inside the brain.

    abstract::Iron, an essential element for all cells of the body, including those of the brain, is transported bound to transferrin in the blood and the general extracellular fluid of the body. The demonstration of transferrin receptors on brain capillary endothelial cells (BCECs) more than 20 years ago provided the evidence for ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章,评审

    doi:10.1111/j.1471-4159.2007.04976.x

    authors: Moos T,Rosengren Nielsen T,Skjørringe T,Morgan EH

    更新日期:2007-12-01 00:00:00

  • CSF proteomic analysis reveals persistent iron deficiency-induced alterations in non-human primate infants.

    abstract::Iron deficiency (ID) anemia during infancy results in long-term neurological consequences, yet the mediating mechanisms remain unclear. Infant monkeys often become naturally anemic during the first 6 months of life, presenting an opportunity to determine the effect of developmental iron deficiency. After weaning, anim...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2007.05113.x

    authors: Geguchadze RN,Coe CL,Lubach GR,Clardy TW,Beard JL,Connor JR

    更新日期:2008-04-01 00:00:00

  • Bradykinin induces interleukin-6 expression in astrocytes through activation of nuclear factor-kappaB.

    abstract::Bradykinin, a mediator of inflammation, is produced in the brain during trauma and stroke. It is thought to open the blood-brain barrier, although the mechanism is unclear. We have investigated, therefore, the effect of bradykinin on the expression of interleukin-6 (IL-6), a putative modulator of the blood-brain barri...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1999.0731461.x

    authors: Schwaninger M,Sallmann S,Petersen N,Schneider A,Prinz S,Libermann TA,Spranger M

    更新日期:1999-10-01 00:00:00

  • Noninvasive in vivo demonstration of 2-fluoro-2-deoxy-D-glucose metabolism beyond the hexokinase reaction in rat brain by 19F nuclear magnetic resonance spectroscopy.

    abstract::The metabolism of 2-fluoro-2-deoxy-D-glucose (FDG) in vivo was observed noninvasively in rat brain using 19F nuclear magnetic resonance (NMR) spectroscopy following an intravenous injection of FDG (400 mg/kg). At 3 h after infusion, four resonances with discrete chemical shifts were resolved. Chemical shift analysis o...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1986.tb12945.x

    authors: Nakada T,Kwee IL,Conboy CB

    更新日期:1986-01-01 00:00:00

  • Changes in NMDA receptor subunit expression in response to contusive spinal cord injury.

    abstract::Differential assembly of N-methyl-D-aspartate (NMDA) receptor subunits determines their functional characteristics. Using in situ hybridization, we found a selective increase of the subunits NR1 and NR2A mRNA at 24 h in ventral motor neurons (VMN) caudal to a standardized spinal cord contusion injury (SCI). Other neur...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.2000.0750174.x

    authors: Grossman SD,Wolfe BB,Yasuda RP,Wrathall JR

    更新日期:2000-07-01 00:00:00

  • Bovine P2 protein: sequence at the NH2-terminal of the protein.

    abstract::Sequence data from key fragments of the P2 protein established the order of cyanogen bromide (CNBr) peptides in the structure of the protein and the primary structure for approximately one-half of the molecule. Data were obtained from the three tryptic peptides of blocked NH2-terminal CNBr peptide (CN3), the large CNB...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1980.tb06276.x

    authors: Weise MJ,Hsieh DL,Levit S,Brostoff SW

    更新日期:1980-08-01 00:00:00

  • Increased glutaminyl cyclase activity in brains of Alzheimer's disease individuals.

    abstract::Glutaminyl cyclases (QC) catalyze the formation of neurotoxic pGlu-modified amyloid-β peptides found in the brains of people with Alzheimer's disease (AD). Reports of several-fold increases in soluble QC (sQC) expression in the brain and peripheral circulation of AD individuals has prompted the development of QC inhib...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/jnc.15114

    authors: Gunn AP,Wong BX,McLean C,Fowler C,Barnard PJ,Duce JA,Roberts BR,AIBL Research Group.

    更新日期:2020-07-02 00:00:00

  • D-aspartate in human brain.

    abstract::The presence of the biologically uncommon D-aspartic acid (D-aspartate) in human brain white matter has been previously reported. The earlier study has now been expanded to include D/L-aspartate ratios from 67 normal brains. The data show that the D-aspartate content increases rapidly from 1 year to approximately 35 y...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1987.tb04122.x

    authors: Man EH,Fisher GH,Payan IL,Cadilla-Perezrios R,Garcia NM,Chemburkar R,Arends G,Frey WH 2nd

    更新日期:1987-02-01 00:00:00

  • Carrier-mediated release of serotonin by 3,4-methylenedioxymethamphetamine: implications for serotonin-dopamine interactions.

    abstract::In vivo microdialysis was used to determine whether the 3,4-methylenedioxymethamphetamine (MDMA)-induced release of serotonin (5-HT) in vivo involves a carrier-mediated process and to investigate further the state-dependent interaction between 5-HT and dopamine. MDMA produced a dose-dependent increase in the extracell...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1996.66010243.x

    authors: Gudelsky GA,Nash JF

    更新日期:1996-01-01 00:00:00

  • Changes in extracellular amino acids during soman- and kainic acid-induced seizures.

    abstract::Extracellular amino acid levels in the rat piriform cortex, an area highly susceptible to seizure-induced neuropathology, were determined by means of intracranial microdialysis. Seizures were induced by systemic administration of either soman (O-1,2,2-trimethylpropyl methylphosphonofluoridate), a potent inhibitor of a...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1987.tb02912.x

    authors: Wade JV,Samson FE,Nelson SR,Pazdernik TL

    更新日期:1987-08-01 00:00:00

  • Hexose translocation across the blood-brain interface: configurational aspects.

    abstract::The translocation of intravenously administered tritiated 3-O-methyl-D-glucopyranose (3-OMG) into brain has been studied in an intact nephrectomized rat preparation by infusing a series of hexoses into one internal carotid artery. 3-OMG rapidly penetrated into brain with peak concentrations, attained 5-8 min after inj...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1968.tb10333.x

    authors: Bidder TG

    更新日期:1968-08-01 00:00:00

  • Isolation and biochemical characterization of a neural proteoglycan expressing the L5 carbohydrate epitope.

    abstract::The monoclonal L5 antibody reacts with an N-glycosidically linked carbohydrate structure which is present on the neural cell adhesion molecule L1, neural chondroitin sulfate proteoglycans, and other not yet identified glycosylated proteins. Using this antibody, we isolated and characterized proteoglycans from adult mo...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1990.tb04931.x

    authors: Streit A,Faissner A,Gehrig B,Schachner M

    更新日期:1990-11-01 00:00:00