TY - JOUR
T1 - Antioxidant compound supplementation prevents oxidative damage in a Drosophila model of Parkinson's disease
AU - Casani, Sandra
AU - Gómez-Pastor, Rocío
AU - Matallana, Emilia
AU - Paricio, Nuria
PY - 2013
Y1 - 2013
N2 - Loss-of-function mutations in the DJ-1 gene are linked to rare autosomal recessive forms of parkinsonism. In Drosophila, two DJ-1 orthologs have been identified, DJ-1α and DJ-1β. Several studies have shown that DJ-1β mutant flies are viable and fertile but exhibit age-dependent locomotor defects, shortened life span, and enhanced sensitivity to toxins that induce oxidative stress response compared to control flies. We also demonstrated that long-term dietary supplementation with antioxidant compounds was effective at increasing life-span values of DJ-1β mutants. These results, together with high levels of oxidative stress markers detected in newly eclosed DJ-1β mutant flies compared to controls, led to the proposal that the life-span phenotype was in part due to defects in the oxidative stress response. To further demonstrate this assumption, we analyzed in detail several markers of oxidative stress in control and DJ-1β mutant flies, either untreated or treated with antioxidant compounds. First, we quantified global reactive oxygen species (ROS) as well as H2O2 production; next we measured the activity of several enzymes that respond to oxidative stress such as catalase and superoxide dismutase; and finally we determined protein oxidative damage. Our results showed that DJ-1β mutants exhibit elevated ROS production and protein oxidative damage as well as decreased antioxidant enzyme activity compared to control flies of the same age, which is consistent with the proposed protective role of DJ-1β against oxidative stress. We found that supplementation with either α-tocopherol or the general antioxidant compound ascorbic acid (vitamin C) increased catalase activity and decreased H2O2 and oxidized protein levels in DJ-1β mutants and control flies, but it led to decreased superoxide dismutase activity, maybe as a consequence of a global reduction in oxidative stress. However, α-tocopherol supplementation specifically reduced global ROS production in DJ-1β mutant flies. This study confirms the important role of DJ-1β in oxidative stress response in Drosophila, especially at the level of H 2O2 detoxification, and provides evidence that early antioxidant supplementation is an effective treatment to suppress phenotypes in DJ-1β mutants partly by reducing oxidative damage.
AB - Loss-of-function mutations in the DJ-1 gene are linked to rare autosomal recessive forms of parkinsonism. In Drosophila, two DJ-1 orthologs have been identified, DJ-1α and DJ-1β. Several studies have shown that DJ-1β mutant flies are viable and fertile but exhibit age-dependent locomotor defects, shortened life span, and enhanced sensitivity to toxins that induce oxidative stress response compared to control flies. We also demonstrated that long-term dietary supplementation with antioxidant compounds was effective at increasing life-span values of DJ-1β mutants. These results, together with high levels of oxidative stress markers detected in newly eclosed DJ-1β mutant flies compared to controls, led to the proposal that the life-span phenotype was in part due to defects in the oxidative stress response. To further demonstrate this assumption, we analyzed in detail several markers of oxidative stress in control and DJ-1β mutant flies, either untreated or treated with antioxidant compounds. First, we quantified global reactive oxygen species (ROS) as well as H2O2 production; next we measured the activity of several enzymes that respond to oxidative stress such as catalase and superoxide dismutase; and finally we determined protein oxidative damage. Our results showed that DJ-1β mutants exhibit elevated ROS production and protein oxidative damage as well as decreased antioxidant enzyme activity compared to control flies of the same age, which is consistent with the proposed protective role of DJ-1β against oxidative stress. We found that supplementation with either α-tocopherol or the general antioxidant compound ascorbic acid (vitamin C) increased catalase activity and decreased H2O2 and oxidized protein levels in DJ-1β mutants and control flies, but it led to decreased superoxide dismutase activity, maybe as a consequence of a global reduction in oxidative stress. However, α-tocopherol supplementation specifically reduced global ROS production in DJ-1β mutant flies. This study confirms the important role of DJ-1β in oxidative stress response in Drosophila, especially at the level of H 2O2 detoxification, and provides evidence that early antioxidant supplementation is an effective treatment to suppress phenotypes in DJ-1β mutants partly by reducing oxidative damage.
KW - α-Tocopherol
KW - Catalase
KW - DJ-1β
KW - Drosophila
KW - Free radicals
KW - Oxidative stress
KW - Parkinson's disease
KW - Protein oxidation
KW - Reactive oxygen species
KW - Superoxide dismutase
KW - Vitamin C
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UR - http://www.scopus.com/inward/citedby.url?scp=84877082059&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2013.03.021
DO - 10.1016/j.freeradbiomed.2013.03.021
M3 - Article
AN - SCOPUS:84877082059
SN - 0891-5849
VL - 61
SP - 151
EP - 160
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
ER -