oxidants and antioxidants in biology - Oxygen Club of California

Amyloid- and H 2 O 2 induced impairment of the
glutathione cycle: Involvement of oxidative stress
SANDRA CARDOSO, A. CRISTINA REGO AND
CATARINA R. OLIVEIRA
Institute of Biochemistry, Faculty of Medicine and Center for Neuroscience and
Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal
Oxidative stress has been implicated in Alzheimer's disease
due, in part, to the action of amyloid β-peptide (Aβ). We observed
that Aβ 25-35 induced an increase in reactive oxygen species
(ROS) in NT2 ρ + cells, leading to protein and lipid oxidation. This
oxidative status was partially prevented by the antioxidants, vitamin
E, reduced glutathione, and by melatonin. Upon Aβ 25-35
treatment, in ρ + cells, a decrease in glutathione reductase activity
and in GSH levels was observed, whereas glutathione peroxidase
activity was shown to be increased. However, NT2 ρ 0 cells (that
lack mitochondrial DNA), in the absence of Aβ, showed an increase
in ROS production, lipid and protein oxidation, as compared
with parental ρ + cells. In NT2 ρ 0 cells, in the absence of Aβ, GSH
levels were maintained, whereas glutathione reductase and peroxidase
activities were increased. The exposure of ρ 0 cells to Aβ did
not induce any significant change in these parameters. Because Aβinduced
cell toxicity may occur independently of generation of
ROS, we have also analysed the regulation of enzymes of the glutathione
cycle in ρ0 and ρ+ exposed to H 2 O 2 . H 2 O 2 induced an
over-stimulation of glutathione reductase activity. An improved
antioxidant status in ρ0 cells was shown to explain a decreased
formation of intracellular hydroperoxides and protein carbonyl
groups induced by a brief exposure to H 2 O 2 . Considering the evidences
presented, we argue that Aβ-induced toxicity is mitochondria
specific and involves other aspects than oxidative stress.
Supported by Fundação para a Ciência e Tecnologia, Portugal.
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