Mitochondrial abnormalities in cybrid cell models of sporadic Alzheimer's disease worsen with passage in culture
We created and studied new cybrid cell lines from sporadic Alzheimer's disease (SAD) or control (CTL) subjects to assess mitochondrial abnormalities just after metabolic selection (“early passage”) and again six passages later (“late passage”). Cytochrome oxidase (CO) activities in early passag...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2004-02-01
|
| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S096999610300192X |
| _version_ | 1818673316801544192 |
|---|---|
| author | Patricia A. Trimmer Paula M. Keeney M.Kate Borland Frederic A. Simon Jatanna Almeida Russell H. Swerdlow Janice P. Parks W.Davis Parker, Jr. James P. Bennett, Jr. |
| author_facet | Patricia A. Trimmer Paula M. Keeney M.Kate Borland Frederic A. Simon Jatanna Almeida Russell H. Swerdlow Janice P. Parks W.Davis Parker, Jr. James P. Bennett, Jr. |
| author_sort | Patricia A. Trimmer |
| collection | DOAJ |
| description | We created and studied new cybrid cell lines from sporadic Alzheimer's disease (SAD) or control (CTL) subjects to assess mitochondrial abnormalities just after metabolic selection (“early passage”) and again six passages later (“late passage”). Cytochrome oxidase (CO) activities in early passage SAD cybrids created independently from the same platelet samples were highly correlated. Early passage SAD and CTL cybrids showed equivalent mitochondrial morphologies. Late passage SAD cybrids showed increased mitochondrial number, reduced mitochondrial size, and an approximately eightfold increase in morphologically abnormal mitochondria. Deficiency of SAD cybrid mitochondrial membrane potentials (ΔΨM) increased with passage. Mitochondrial bromodeoxyuridine (BrdU) uptake to estimate mitochondrial DNA (mtDNA) synthesis did not change with passage in CTL but increased in SAD cybrids. With time in culture, SAD mtDNA appears to replicate faster in cybrids, yielding cells with relative worsening of bioenergetic function. Metabolically deleterious SAD mitochondrial genes, like those in yeast, may have a replicative advantage over nondeleterious mitochondrial genes that assume dominance in CTL cybrids. |
| first_indexed | 2024-12-17T07:53:52Z |
| format | Article |
| id | doaj.art-d51c8a53b34e40b289bba1b586bc0bad |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T07:53:52Z |
| publishDate | 2004-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-d51c8a53b34e40b289bba1b586bc0bad2022-12-21T21:57:46ZengElsevierNeurobiology of Disease1095-953X2004-02-011512939Mitochondrial abnormalities in cybrid cell models of sporadic Alzheimer's disease worsen with passage in culturePatricia A. Trimmer0Paula M. Keeney1M.Kate Borland2Frederic A. Simon3Jatanna Almeida4Russell H. Swerdlow5Janice P. Parks6W.Davis Parker, Jr.7James P. Bennett, Jr.8Center for the Study of Neurodegenerative Diseases, University of Virginia School of Medicine, Charlottesville, VA, USA; Department of Neurology, University of Virginia School of Medicine, Charlottesville, VA, USA; Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA, USACenter for the Study of Neurodegenerative Diseases, University of Virginia School of Medicine, Charlottesville, VA, USA; Department of Neurology, University of Virginia School of Medicine, Charlottesville, VA, USA; Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA, USACenter for the Study of Neurodegenerative Diseases, University of Virginia School of Medicine, Charlottesville, VA, USA; Department of Neurology, University of Virginia School of Medicine, Charlottesville, VA, USA; Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA, USACenter for the Study of Neurodegenerative Diseases, University of Virginia School of Medicine, Charlottesville, VA, USA; Department of Neurology, University of Virginia School of Medicine, Charlottesville, VA, USA; Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA, USACenter for the Study of Neurodegenerative Diseases, University of Virginia School of Medicine, Charlottesville, VA, USA; Department of Neurology, University of Virginia School of Medicine, Charlottesville, VA, USA; Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA, USACenter for the Study of Neurodegenerative Diseases, University of Virginia School of Medicine, Charlottesville, VA, USA; Department of Neurology, University of Virginia School of Medicine, Charlottesville, VA, USA; Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA, USACenter for the Study of Neurodegenerative Diseases, University of Virginia School of Medicine, Charlottesville, VA, USA; Department of Neurology, University of Virginia School of Medicine, Charlottesville, VA, USA; Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA, USACenter for the Study of Neurodegenerative Diseases, University of Virginia School of Medicine, Charlottesville, VA, USA; Department of Neurology, University of Virginia School of Medicine, Charlottesville, VA, USA; Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA, USACenter for the Study of Neurodegenerative Diseases, University of Virginia School of Medicine, Charlottesville, VA, USA; Department of Neurology, University of Virginia School of Medicine, Charlottesville, VA, USA; Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA, USAWe created and studied new cybrid cell lines from sporadic Alzheimer's disease (SAD) or control (CTL) subjects to assess mitochondrial abnormalities just after metabolic selection (“early passage”) and again six passages later (“late passage”). Cytochrome oxidase (CO) activities in early passage SAD cybrids created independently from the same platelet samples were highly correlated. Early passage SAD and CTL cybrids showed equivalent mitochondrial morphologies. Late passage SAD cybrids showed increased mitochondrial number, reduced mitochondrial size, and an approximately eightfold increase in morphologically abnormal mitochondria. Deficiency of SAD cybrid mitochondrial membrane potentials (ΔΨM) increased with passage. Mitochondrial bromodeoxyuridine (BrdU) uptake to estimate mitochondrial DNA (mtDNA) synthesis did not change with passage in CTL but increased in SAD cybrids. With time in culture, SAD mtDNA appears to replicate faster in cybrids, yielding cells with relative worsening of bioenergetic function. Metabolically deleterious SAD mitochondrial genes, like those in yeast, may have a replicative advantage over nondeleterious mitochondrial genes that assume dominance in CTL cybrids.http://www.sciencedirect.com/science/article/pii/S096999610300192XAlzheimer's diseaseCybridsmtDNABioenergetic phenotypeReplicative advantage |
| spellingShingle | Patricia A. Trimmer Paula M. Keeney M.Kate Borland Frederic A. Simon Jatanna Almeida Russell H. Swerdlow Janice P. Parks W.Davis Parker, Jr. James P. Bennett, Jr. Mitochondrial abnormalities in cybrid cell models of sporadic Alzheimer's disease worsen with passage in culture Neurobiology of Disease Alzheimer's disease Cybrids mtDNA Bioenergetic phenotype Replicative advantage |
| title | Mitochondrial abnormalities in cybrid cell models of sporadic Alzheimer's disease worsen with passage in culture |
| title_full | Mitochondrial abnormalities in cybrid cell models of sporadic Alzheimer's disease worsen with passage in culture |
| title_fullStr | Mitochondrial abnormalities in cybrid cell models of sporadic Alzheimer's disease worsen with passage in culture |
| title_full_unstemmed | Mitochondrial abnormalities in cybrid cell models of sporadic Alzheimer's disease worsen with passage in culture |
| title_short | Mitochondrial abnormalities in cybrid cell models of sporadic Alzheimer's disease worsen with passage in culture |
| title_sort | mitochondrial abnormalities in cybrid cell models of sporadic alzheimer s disease worsen with passage in culture |
| topic | Alzheimer's disease Cybrids mtDNA Bioenergetic phenotype Replicative advantage |
| url | http://www.sciencedirect.com/science/article/pii/S096999610300192X |
| work_keys_str_mv | AT patriciaatrimmer mitochondrialabnormalitiesincybridcellmodelsofsporadicalzheimersdiseaseworsenwithpassageinculture AT paulamkeeney mitochondrialabnormalitiesincybridcellmodelsofsporadicalzheimersdiseaseworsenwithpassageinculture AT mkateborland mitochondrialabnormalitiesincybridcellmodelsofsporadicalzheimersdiseaseworsenwithpassageinculture AT fredericasimon mitochondrialabnormalitiesincybridcellmodelsofsporadicalzheimersdiseaseworsenwithpassageinculture AT jatannaalmeida mitochondrialabnormalitiesincybridcellmodelsofsporadicalzheimersdiseaseworsenwithpassageinculture AT russellhswerdlow mitochondrialabnormalitiesincybridcellmodelsofsporadicalzheimersdiseaseworsenwithpassageinculture AT janicepparks mitochondrialabnormalitiesincybridcellmodelsofsporadicalzheimersdiseaseworsenwithpassageinculture AT wdavisparkerjr mitochondrialabnormalitiesincybridcellmodelsofsporadicalzheimersdiseaseworsenwithpassageinculture AT jamespbennettjr mitochondrialabnormalitiesincybridcellmodelsofsporadicalzheimersdiseaseworsenwithpassageinculture |