Is differential regulation of mitochondrial transcripts in Parkinson's disease related to apoptosis?
Identifieur interne : 004431 ( Main/Exploration ); précédent : 004430; suivant : 004432Is differential regulation of mitochondrial transcripts in Parkinson's disease related to apoptosis?
Auteurs : M. Ruberg [France] ; B. Brugg [France] ; A. Prigent [France] ; E. Hirsch [France] ; A. Brice [France] ; Yves Agid [France]Source :
- Journal of neurochemistry [ 0022-3042 ] ; 1997.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
- Aged, Aged, 80 and over, Apoptosis, Complementary DNA, DNA, Complementary (genetics), Dopaminergic neuron, Female, Gene Library, Gene expression, Human, Humans, In Situ Hybridization, Locus niger, Male, Messenger RNA, Mitochondria (physiology), Mitochondrial DNA, Parkinson Disease (genetics), Parkinson Disease (pathology), Parkinson disease, Substantia Nigra (physiopathology), Transcription, Transcription, Genetic, Tumor Necrosis Factor-alpha (pharmacology), Tumor necrosis factor.
- MESH :
- chemical , genetics : DNA, Complementary.
- genetics : Parkinson Disease.
- pathology : Parkinson Disease.
- chemical , pharmacology : Tumor Necrosis Factor-alpha.
- physiology : Mitochondria.
- physiopathology : Substantia Nigra.
- Aged, Aged, 80 and over, Apoptosis, Female, Gene Library, Humans, In Situ Hybridization, Male, Transcription, Genetic.
Abstract
A cDNA library of substantia nigra pars compacta from a patient with Parkinson's disease (PD) was differentially screened with probes of normal and parkinsonian substantia nigra enriched in neuronal transcripts. Fifty-eight clones were isolated; 39 were subunits of mitochondrial respiratory complexes I and IV. Parallel screening of a cDNA library derived from normal substantia nigra confirmed differential representation of the transcripts in the substantia nigra pars compacta. In situ hybridization in postmortem brain from parkinsonian and control subjects, with representative complex I and complex IV probes, showed increased labeling, at the cellular level, of the complex I subunit ND1 in neurons of the lateral substantia nigra, where cell death is greatest in PD, but decreased labeling in the medial substantia nigra where fewer cells die. Expression of a complex IV subunit, COXI, increased, however, in both parts of the structure. Increased expression of ND1 and COXI was also observed in nerve growth factor-differentiated PC12 cells undergoing apoptosis induced by tumor necrosis factor-α, suggesting that the differential regulation of certain mitochondrial mRNAs may be associated with this form of cell death. This in vitro model of apoptosis is potentially relevant to the death of dopaminergic neurons in PD, because these cells express the tumor necrosis factor-α receptor, and neighboring microglial cells in patients synthesize the cytokine.
Affiliations:
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Le document en format XML
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<term>Apoptosis</term>
<term>Complementary DNA</term>
<term>DNA, Complementary (genetics)</term>
<term>Dopaminergic neuron</term>
<term>Female</term>
<term>Gene Library</term>
<term>Gene expression</term>
<term>Human</term>
<term>Humans</term>
<term>In Situ Hybridization</term>
<term>Locus niger</term>
<term>Male</term>
<term>Messenger RNA</term>
<term>Mitochondria (physiology)</term>
<term>Mitochondrial DNA</term>
<term>Parkinson Disease (genetics)</term>
<term>Parkinson Disease (pathology)</term>
<term>Parkinson disease</term>
<term>Substantia Nigra (physiopathology)</term>
<term>Transcription</term>
<term>Transcription, Genetic</term>
<term>Tumor Necrosis Factor-alpha (pharmacology)</term>
<term>Tumor necrosis factor</term>
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<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>DNA, Complementary</term>
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<front><div type="abstract" xml:lang="en">A cDNA library of substantia nigra pars compacta from a patient with Parkinson's disease (PD) was differentially screened with probes of normal and parkinsonian substantia nigra enriched in neuronal transcripts. Fifty-eight clones were isolated; 39 were subunits of mitochondrial respiratory complexes I and IV. Parallel screening of a cDNA library derived from normal substantia nigra confirmed differential representation of the transcripts in the substantia nigra pars compacta. In situ hybridization in postmortem brain from parkinsonian and control subjects, with representative complex I and complex IV probes, showed increased labeling, at the cellular level, of the complex I subunit ND1 in neurons of the lateral substantia nigra, where cell death is greatest in PD, but decreased labeling in the medial substantia nigra where fewer cells die. Expression of a complex IV subunit, COXI, increased, however, in both parts of the structure. Increased expression of ND1 and COXI was also observed in nerve growth factor-differentiated PC12 cells undergoing apoptosis induced by tumor necrosis factor-α, suggesting that the differential regulation of certain mitochondrial mRNAs may be associated with this form of cell death. This in vitro model of apoptosis is potentially relevant to the death of dopaminergic neurons in PD, because these cells express the tumor necrosis factor-α receptor, and neighboring microglial cells in patients synthesize the cytokine.</div>
</front>
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