Increased transcription and activity of glutathione synthase in response to deficiencies in folate, vitamin E, and apolipoprotein E.
J Neurosci Res
; 75(4): 508-15, 2004 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-14743434
ABSTRACT
Oxidative stress is a major contributing factor in neurodegeneration and can arise from dietary, environmental, and genetic sources. Here we examine the separate and combined impact of deprivation of folate and vitamin E, coupled with dietary iron as a prooxidant, on normal mice and transgenic mice lacking apolipoprotein E (ApoE-/- mice). Both mouse strains exhibited increased levels of glutathione when deprived of folate and vitamin E, but a substantial further increase was observed in ApoE-/- mice. To determine the mechanism(s) underlying this increase, we quantified transcription and activity of glutathione synthase (GS). Both normal and ApoE-/- mice demonstrated increased GS activity when deprived of folate and vitamin E. However, transcription was increased only in ApoE-/- mice deprived of folate and vitamin E. These findings demonstrate that deficiency in one gene can result in compensatory up-regulation in a second relevant gene and, furthermore, indicate that compensation for oxidative stress can occur in brain tissue at epigenetic and genetic levels depending on the nature and/or extent of oxidative stress.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Apolipoproteínas E
/
Transcrição Gênica
/
Deficiência de Vitamina E
/
Deficiência de Ácido Fólico
/
Glutationa Sintase
Limite:
Animals
Idioma:
En
Revista:
J Neurosci Res
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Estados Unidos