Anti-apoptotic proteins are oxidized by Abeta25-35 in Alzheimer's fibroblasts.
We have examined the effects of the beta-amyloid peptide (Abeta(25-35)) on fibroblasts derived from subjects with Alzheimer's disease (AD) and from age-matched controls. The peptide was significantly more cytotoxic to the AD-derived fibroblasts. The level of protein oxidation was also greater in the cells from AD subjects. Two-dimensional electrophoresis (2-DE) coupled with immunostaining for protein carbonylation revealed specific oxidation-sensitive proteins (OSPs) in both the control and AD-derived cells. Two specific OSPs were identified by mass spectrometry as heat shock protein 60 (HSP 60) and vimentin. Exposure of the cells to Abeta(25-35) resulted in a twofold increase in the level of oxidation of these two OSPs in the cells derived from controls, but a ninefold increase in their level of oxidation in the fibroblasts from AD subjects. These observations are of particular interest because of the proposed anti-apoptotic roles of both HSP 60 and vimentin and our recent observation that these same two proteins are particularly susceptible to oxidation in neuronally derived cells.
Choi
Joungil
J
Molecular Aging Unit, Department of Molecular Biology and Immunology, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX 76107, USA.
Malakowsky
Christina A
CA
Talent
John M
JM
Conrad
Craig C
CC
Carroll
Christopher A
CA
Weintraub
Susan T
ST
Gracy
Robert W
RW
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D002470:Cell Survival; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000032:analysis / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D005347:Fibroblasts; D006801:Humans; D007120:Immunochemistry; D013058:Mass Spectrometry; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000494:pharmacology*; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D014746:Vimentin / Q000032:analysis / Q000378:metabolism
D016229:Amyloid beta-Peptides; D018834:Chaperonin 60; D010446:Peptide Fragments; D011506:Proteins; D014746:Vimentin