Platelet cytochrome oxidase and citrate synthase activities in APOE ε4 carrier and non-carrier Alzheimer's disease patients
A degradation product of APOE ε4-encoded apolipoprotein E protein targets mitochondria and inhibits cytochrome oxidase (COX), and autopsy brains from young adult APOE ε4 carriers show reduced COX activity. To further explore relationships between APOE alleles and COX, we measured platelet mitochondr...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2017-08-01
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| Series: | Redox Biology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231717302422 |
| _version_ | 1818955859081822208 |
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| author | Heather M. Wilkins Scott J. Koppel Rebecca Bothwell Jonathan Mahnken Jeffrey M. Burns Russell H. Swerdlow |
| author_facet | Heather M. Wilkins Scott J. Koppel Rebecca Bothwell Jonathan Mahnken Jeffrey M. Burns Russell H. Swerdlow |
| author_sort | Heather M. Wilkins |
| collection | DOAJ |
| description | A degradation product of APOE ε4-encoded apolipoprotein E protein targets mitochondria and inhibits cytochrome oxidase (COX), and autopsy brains from young adult APOE ε4 carriers show reduced COX activity. To further explore relationships between APOE alleles and COX, we measured platelet mitochondria COX activity in AD subjects with (n=8) and without (n=7) an APOE ε4 allele and found the mean COX activity, when normalized to sample total protein, was lower in the APOE ε4 carriers (p<0.05). Normalizing COX activity to citrate synthase (CS) activity eliminated this difference, but notably the mean CS activity was itself lower in the APOE ε4 carriers (p<0.05). COX and CS protein levels did not appear to cause the lower APOE ε4 carrier COX and CS Vmax activities. If confirmed in larger studies, these data could suggest mitochondria at least partly mediate the well-recognized association between APOE alleles and AD risk. Keywords: Alzheimer's disease, Apolipoprotein E, Biomarker, Cytochrome oxidase, Citrate synthase, Mitochondria, Translocase of the outer mitochondrial membrane 40 |
| first_indexed | 2024-12-20T10:44:45Z |
| format | Article |
| id | doaj.art-3fb242bd5dfa412eb46e8e0362b281d2 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-12-20T10:44:45Z |
| publishDate | 2017-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-3fb242bd5dfa412eb46e8e0362b281d22022-12-21T19:43:26ZengElsevierRedox Biology2213-23172017-08-0112828832Platelet cytochrome oxidase and citrate synthase activities in APOE ε4 carrier and non-carrier Alzheimer's disease patientsHeather M. Wilkins0Scott J. Koppel1Rebecca Bothwell2Jonathan Mahnken3Jeffrey M. Burns4Russell H. Swerdlow5Department of Neurology University of Kansas Medical Center, Kansas City, KS, USA; University of Kansas Alzheimer's Disease Center, Kansas City, KS, USADepartment of Neurology University of Kansas Medical Center, Kansas City, KS, USA; University of Kansas Alzheimer's Disease Center, Kansas City, KS, USAUniversity of Kansas Alzheimer's Disease Center, Kansas City, KS, USAUniversity of Kansas Alzheimer's Disease Center, Kansas City, KS, USADepartment of Neurology University of Kansas Medical Center, Kansas City, KS, USA; University of Kansas Alzheimer's Disease Center, Kansas City, KS, USADepartment of Neurology University of Kansas Medical Center, Kansas City, KS, USA; University of Kansas Alzheimer's Disease Center, Kansas City, KS, USA; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA; Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS, USA; Corresponding author at: MD University of Kansas School of Medicine MS 2012, Landon Center on Aging 3901, Rainbow Blvd, Kansas City, KS 66160, USA.A degradation product of APOE ε4-encoded apolipoprotein E protein targets mitochondria and inhibits cytochrome oxidase (COX), and autopsy brains from young adult APOE ε4 carriers show reduced COX activity. To further explore relationships between APOE alleles and COX, we measured platelet mitochondria COX activity in AD subjects with (n=8) and without (n=7) an APOE ε4 allele and found the mean COX activity, when normalized to sample total protein, was lower in the APOE ε4 carriers (p<0.05). Normalizing COX activity to citrate synthase (CS) activity eliminated this difference, but notably the mean CS activity was itself lower in the APOE ε4 carriers (p<0.05). COX and CS protein levels did not appear to cause the lower APOE ε4 carrier COX and CS Vmax activities. If confirmed in larger studies, these data could suggest mitochondria at least partly mediate the well-recognized association between APOE alleles and AD risk. Keywords: Alzheimer's disease, Apolipoprotein E, Biomarker, Cytochrome oxidase, Citrate synthase, Mitochondria, Translocase of the outer mitochondrial membrane 40http://www.sciencedirect.com/science/article/pii/S2213231717302422 |
| spellingShingle | Heather M. Wilkins Scott J. Koppel Rebecca Bothwell Jonathan Mahnken Jeffrey M. Burns Russell H. Swerdlow Platelet cytochrome oxidase and citrate synthase activities in APOE ε4 carrier and non-carrier Alzheimer's disease patients Redox Biology |
| title | Platelet cytochrome oxidase and citrate synthase activities in APOE ε4 carrier and non-carrier Alzheimer's disease patients |
| title_full | Platelet cytochrome oxidase and citrate synthase activities in APOE ε4 carrier and non-carrier Alzheimer's disease patients |
| title_fullStr | Platelet cytochrome oxidase and citrate synthase activities in APOE ε4 carrier and non-carrier Alzheimer's disease patients |
| title_full_unstemmed | Platelet cytochrome oxidase and citrate synthase activities in APOE ε4 carrier and non-carrier Alzheimer's disease patients |
| title_short | Platelet cytochrome oxidase and citrate synthase activities in APOE ε4 carrier and non-carrier Alzheimer's disease patients |
| title_sort | platelet cytochrome oxidase and citrate synthase activities in apoe ε4 carrier and non carrier alzheimer s disease patients |
| url | http://www.sciencedirect.com/science/article/pii/S2213231717302422 |
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