Mitochondrial-dependent apoptosis in Huntington's disease human cybrids.

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Abstrakt

Tytuł:: Mitochondrial-dependent apoptosis in Huntington's disease human cybrids.
Autorzy:: Ferreira IL; Center for Neuroscience and Cell Biology, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal.
Nascimento MV
Ribeiro M
Almeida S
Cardoso SM
Grazina M
Pratas J
Santos MJ
Januário C
Oliveira CR
Rego AC
Źródło:: Experimental neurology [Exp Neurol] 2010 Apr; Vol. 222 (2), pp. 243-55. Date of Electronic Publication: 2010 Jan 14.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Publication: Orlando Fl : Academic Press
Original Publication: New York.
MeSH Terms:: Apoptosis/*physiology
Huntington Disease/*pathology
Huntington Disease/*physiopathology
Mitochondria/*metabolism
Multienzyme Complexes/*metabolism
Adult ; Analysis of Variance ; Apoptosis/drug effects ; Apoptosis Inducing Factor/metabolism ; Apoptosis Regulatory Proteins/metabolism ; Bcl-2-Like Protein 11 ; Case-Control Studies ; Caspase 3/metabolism ; Cell Line, Tumor ; Citrate (si)-Synthase/metabolism ; DNA, Mitochondrial/metabolism ; Dose-Response Relationship, Drug ; Electron Transport Complex III/metabolism ; Electron Transport Complex IV/metabolism ; Enzyme Inhibitors/pharmacology ; Gene Expression Regulation/drug effects ; Gene Expression Regulation/genetics ; Humans ; Huntington Disease/genetics ; Intracellular Fluid/metabolism ; L-Lactate Dehydrogenase/metabolism ; Membrane Potential, Mitochondrial/drug effects ; Membrane Potential, Mitochondrial/genetics ; Membrane Potential, Mitochondrial/physiology ; Membrane Proteins/metabolism ; Mitochondria/drug effects ; Nitrobenzoates/pharmacology ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Reactive Oxygen Species/metabolism ; Staurosporine/pharmacology ; Subcellular Fractions/metabolism ; Superoxides/metabolism ; Teratocarcinoma ; Time Factors ; Trinucleotide Repeat Expansion/genetics ; bcl-2 Homologous Antagonist-Killer Protein/metabolism ; bcl-2-Associated X Protein/metabolism
Substance Nomenclature:: 0 (Apoptosis Inducing Factor)
0 (Apoptosis Regulatory Proteins)
0 (BCL2L11 protein, human)
0 (Bcl-2-Like Protein 11)
0 (DNA, Mitochondrial)
0 (Enzyme Inhibitors)
0 (Membrane Proteins)
0 (Multienzyme Complexes)
0 (Nitrobenzoates)
0 (Proto-Oncogene Proteins)
0 (Proto-Oncogene Proteins c-bcl-2)
0 (Reactive Oxygen Species)
0 (bcl-2 Homologous Antagonist-Killer Protein)
0 (bcl-2-Associated X Protein)
11062-77-4 (Superoxides)
EC 1.1.1.27 (L-Lactate Dehydrogenase)
EC 1.9.3.1 (Electron Transport Complex IV)
EC 2.3.3.1 (Citrate (si)-Synthase)
EC 3.4.22.- (Caspase 3)
EC 7.1.1.8 (Electron Transport Complex III)
H318ZW7612 (3-nitrobenzoic acid)
H88EPA0A3N (Staurosporine)
Entry Date(s):: Date Created: 20100119 Date Completed: 20100326 Latest Revision: 20220408
Update Code:: 20240104
DOI:: 10.1016/j.expneurol.2010.01.002
PMID:: 20079354
: Czasopismo naukowe

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We investigated the involvement of mitochondrial-dependent apoptosis in Huntington's disease (HD) vs. control (CTR) cybrids, obtained from the fusion of human platelets with mitochondrial DNA-depleted NT2 cells, and further exposed to 3-nitropropionic acid (3-NP) or staurosporine (STS). Untreated HD cybrids did not exhibit significant modifications in the activity of mitochondrial respiratory chain complexes I-IV or in mtDNA sequence variations suggestive of a primary role in mitochondrial susceptibility in the subpopulation of HD carriers studied. However, a slight decrease in mitochondrial membrane potential and increased formation of intracellular hydroperoxides was observed in HD cybrids under basal conditions. Furthermore, apoptotic nuclei morphology and a moderate increase in caspase-3 activation, as well as increased levels of superoxide ions and hydroperoxides were observed in HD cybrids upon 3-NP or STS treatment. 3-NP-evoked apoptosis in HD cybrids involved cytochrome c and AIF release from mitochondria, which was associated with mitochondrial Bax translocation. CTR cybrids subjected to 3-NP showed increased mitochondrial Bax and Bim levels and the release of AIF, but not cytochrome c, suggesting a different mode of cell death, linked to the loss of membrane integrity. Additionally, increased mitochondrial Bim and Bak levels, and a slight release of cytochrome c in untreated HD cybrids may help to explain their moderate susceptibility to mitochondrial-dependent apoptosis.
(Copyright 2010 Elsevier Inc. All rights reserved.)

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