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 Neurochemjournal_title
Journal of neurochemistryauthors
Hsu M,Srinivas B,Kumar J,Subramanian R,Andersen Jdoi
10.1111/j.1471-4159.2004.02929.xkeywords:
subject
Has Abstractpub_date
2005-03-01 00:00:00pages
1091-103issue
5eissn
0022-3042issn
1471-4159pii
JNC2929journal_volume
92pub_type
杂志文章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
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journal_title:Journal of neurochemistry
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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
更新日期:2014-08-01 00:00:00
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
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更新日期:1991-12-01 00:00:00
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更新日期:2004-08-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.12684
更新日期:2014-06-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:1989-11-01 00:00:00
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...
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journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
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更新日期:1999-10-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1986.tb12945.x
更新日期:1986-01-01 00:00:00
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...
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pub_type: 杂志文章
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更新日期:2000-07-01 00:00:00
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
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更新日期:1980-08-01 00:00:00
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
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更新日期:2020-07-02 00:00:00
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
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journal_title:Journal of neurochemistry
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更新日期:1996-01-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1987.tb02912.x
更新日期:1987-08-01 00:00:00
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
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更新日期:1968-08-01 00:00:00
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
更新日期:1990-11-01 00:00:00