Vitamin E prevents oxidation of antiapoptotic proteins in neuronal cells.
Oxidative damage to neuronal proteins appears to be central to the toxicity associated with a number of neuropathologies, including Alzheimer's disease. We have examined this by using oxidative stress to induce apoptosis in a mouse hippocampal neuronal cell line (HT-22). Oxidatively modified proteins were measured by high-resolution two-dimensional gel electrophoresis coupled with oxidation-specific immunostains. Under these conditions the oxidatively stressed cells undergo apoptosis, and specific proteins are oxidized. The three proteins that appeared to be most susceptible to oxidation were identified by mass spectrometry. Those oxidized proteins are heat shock protein 60 and vimentin, both believed to function as antiapoptotic proteins, and a third protein with sequence homology to hemoglobin alpha-chain. When the cells were pretreated with vitamin E, these proteins were not oxidized and the cells did not undergo apoptosis.
Choi
Joungil
J
Molecular Aging Unit, Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, Texas, USA.
Conrad
Craig C
CC
Dai
Rong
R
Malakowsky
Christina A
CA
Talent
John M
JM
Carroll
Christopher A
CA
Weintraub
Susan T
ST
Gracy
Robert W
RW
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D018834:Chaperonin 60 / Q000302:isolation & purification / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D006454:Hemoglobins / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011506:Proteins / Q000302:isolation & purification / Q000378:metabolism*; D020543:Proteome / Q000302:isolation & purification / Q000378:metabolism; D014746:Vimentin / Q000302:isolation & purification / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology*
D018834:Chaperonin 60; D006454:Hemoglobins; D011506:Proteins; D020543:Proteome; D014746:Vimentin; D014810:Vitamin E