Hypoxia rescues early mortality conferred by superoxide dismutase deficiency

Wicks, Shawna E.; Bain, Nathan; Duttaroy, Atanu; Hilliker, Arthur J.; Phillips, J. P.

doi:10.1016/j.freeradbiomed.2008.09.036

Cited by 27 publications

(17 citation statements)

References 38 publications

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“…The hypoxic condition by itself has little impact on the survival of Sod2 n283 adults (Fig. 6) same as pointed out earlier by Wicks et al 31 but following the activation of SOD2 with RU486, these flies can now live up to 25 days (average life span) under hypoxic environment, presumably due to reduced oxygen metabolism (Fig. 6).…”

Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tsupporting

confidence: 73%

SOD2, the principal scavenger of mitochondrial superoxide, is dispensable for embryogenesis and imaginal tissue development but essential for adult survival

Mukherjee

Forde

Belton

et al. 2011

Fly

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Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tsupporting

confidence: 73%

SOD2, the principal scavenger of mitochondrial superoxide, is dispensable for embryogenesis and imaginal tissue development but essential for adult survival

Mukherjee

Forde

Belton

et al. 2011

Fly

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“…Our pathophysiological findings highlight the variable tissue-specific oxygen sensitivities of the nose, lung, brain, and heart of Ndufs4 KO mice with diffusely impaired oxidative metabolism across all of their tissues. We speculate that these differences arise from variations in metabolic flexibility, such as the ability to rely on glycolytic ATP production (28–30), or, alternatively, differences in the ability of these tissues to compensate for oxidative stress (31). …”

Section: Discussionmentioning

confidence: 99%

Hypoxia treatment reverses neurodegenerative disease in a mouse model of Leigh syndrome

Ferrari

Jain

Goldberger

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

127

128

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SignificanceInherited or acquired defects in mitochondria lead to devastating disorders for which we have no effective general therapies. We recently reported that breathing normobaric 11% O2 prevents neurodegeneration in a mouse model of a pediatric mitochondrial disease, Leigh syndrome. Here we provide updated survival curves of mice treated with varying doses of oxygen and explore eventual causes of death. We explore alternative hypoxia regimens and report that neither intermittent nor moderate hypoxia regimens suffice to prevent neurological disease. Finally, we show that hypoxia can not only prevent, but also reverses the brain lesions in mice with advanced neuropathology. Our preclinical studies will help guide future clinical studies aimed at harnessing hypoxia as a safe and practical therapy.

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“…UAS-SOD1-IR (or UAS-SOD1-RNAi ), UAS-hSOD1 , and UAS-Ndi1 transgenic flies were described previously (Bahadorani et al, 2010; Parkes et al, 1998; Wicks et al, 2009). UAS-GFP was obtained from the Bloomington Stock Center (stock 1521).…”

Section: Methodsmentioning

confidence: 99%

Expression of zinc-deficient human superoxide dismutase in Drosophila neurons produces a locomotor defect linked to mitochondrial dysfunction

Bahadorani

Mukai

Rabie

et al. 2013

Neurobiology of Aging

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More than 130 different mutations in the Cu/Zn superoxide dismutase (SOD1) gene have been associated with Amyotrophic lateral sclerosis (ALS) but the mechanism of this toxicity remains controversial. To gain insight into the importance of the zinc site in the pathogenesis of SOD1 in vivo, we generated a Drosophila model with transgenic expression of a zinc-deficient human SOD1. Expression of zinc-deficient SOD1 in Drosophila resulted in a progressive movement defect with associated mitochondrial cristae vacuolization and reductions in ATP levels. Furthermore, these flies are sensitized to mitochondrial toxins, paraquat and zinc. Importantly, we show that the zinc-deficient SOD1-induced motor defect can be ameliorated by supplementing the endogenous fly respiratory chain machinery with the single-subunit NADH–ubiquinone oxidoreductase (Ndi1) from yeast. These results demonstrate that zinc-deficient SOD1 is neurotoxic in vivo and suggest that mitochondrial dysfunction plays a critical role in this toxicity. The robust behavioral, pathological and biochemical phenotypes conferred by zinc-deficient SOD1 in Drosophila have general implications for the role of the zinc ion in both familial and sporadic ALS.

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Hypoxia rescues early mortality conferred by superoxide dismutase deficiency

Cited by 27 publications

References 38 publications

SOD2, the principal scavenger of mitochondrial superoxide, is dispensable for embryogenesis and imaginal tissue development but essential for adult survival

SOD2, the principal scavenger of mitochondrial superoxide, is dispensable for embryogenesis and imaginal tissue development but essential for adult survival

Hypoxia treatment reverses neurodegenerative disease in a mouse model of Leigh syndrome

Expression of zinc-deficient human superoxide dismutase in Drosophila neurons produces a locomotor defect linked to mitochondrial dysfunction

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