Vitamin E deficiency does not induce compensatory antioxidant increases in central nervous system tissue of apolipoprotein E-deficient mice.
Compensatory upregulation in endogenous antioxidants has been shown to accompany certain genetic and dietary deficiencies that promote oxidative stress, including that related to Alzheimer's disease. We compared antioxidant levels in brain tissue of normal and transgenic mice lacking apolipoprotein E following dietary deprivation of vitamin E or folate. As described previously, ApoE-deficient mice displayed increased levels of the endogenous antioxidant glutathione as compared to normal mice, and increased these levels further following folate deprivation. By contrast, glutathione was depleted following vitamin E deprivation in brain tissue of normal and ApoE-deficient mice. TBAR analyses confirmed increased oxidative damage following vitamin E deprivation. However, combined deprivation of folate and vitamin E resulted in levels of glutathione intermediate between those observed following deprivation of either agent, indicating that the lack of compensatory increase in glutathione following vitamin E deprivation was not due to overt neurotoxicity. Similar results were observed for total antioxidant levels in brain tissue. The differential response to vitamin E and folate deprivation is consistent with the possibility that specific differences in oxidative damage may result from deficiencies in either of these agents. The lack of a compensatory response to vitamin E deprivation highlights the importance of dietary vitamin E in prevention of chronic neurodegeneration.
Shea
Thomas B
TB
Center for Cellular Neurobiology and Neurodegeneration Research, University of Massachusetts, Lowell, MA 01854, USA. Thomas_Shea@uml.edu
Rogers
Eugene
E
Ashline
David
D
Ortiz
Daniela
D
Duarte
Nancy
N
Wilson
Thomas O
TO
Nicolosi
Robert J
RJ
Sheu
Min-Shyan
MS
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency*; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D002462:Cell Membrane / Q000378:metabolism / Q000473:pathology; D046508:Culture Techniques; D005978:Glutathione / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009410:Nerve Degeneration / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology*; D014811:Vitamin E Deficiency / Q000378:metabolism*
D000975:Antioxidants; D001057:Apolipoproteins E; D005978:Glutathione