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Published Online: 30 April 2014

Manganese-Based Superoxide Dismutase Mimics Modify Both Acute and Long-Term Outcome Severity in a Drosophila melanogaster Model of Classic Galactosemia

Publication: Antioxidants & Redox Signaling
Volume 20, Issue Number 15


Aims: The goal of this study was to use two manganese (Mn)-based superoxide dismutase (SOD) mimics to test the hypothesis that reactive oxygen species contribute to both acute and long-term outcomes in a galactose-1P uridylyltransferase (GALT)-null Drosophila melanogaster model of classic galactosemia. Results: We tested the impact of each of two Mn porphyrin SOD mimics, MnTnBuOE-2-PyP5+, and MnTE-2-PyP5+, (i) on survival of GALT-null Drosophila larvae reared in the presence versus absence of dietary galactose and (ii) on the severity of a long-term movement defect in GALT-null adult flies. Both SOD mimics conferred a significant survival benefit to GALT-null larvae exposed to galactose but not to controls or to GALT-null larvae reared in the absence of galactose. One mimic, MnTE-2-PyP5+, also largely rescued a galactose-independent long-term movement defect otherwise seen in adult GALT-null flies. The survival benefit of both SOD mimics occurred despite continued accumulation of elevated galactose-1P in the treated animals, and studies of thiolated proteins demonstrated that in both the presence and absence of dietary galactose MnTE-2-PyP5+ largely prevented the elevated protein oxidative damage otherwise seen in GALT-null animals relative to controls. Innovation and Conclusions: Our results confirm oxidative stress as a mediator of acute galactose sensitivity in GALT-null Drosophila larvae and demonstrate for the first time that oxidative stress may also contribute to galactose-independent adult outcomes in GALT deficiency. Finally, our results demonstrate for the first time that both MnTnBuOE-2-PyP5+ and MnTE-2-PyP5+ are bioavailable and effective when administered through an oral route in a D. melanogaster model of classic galactosemia. Antioxid. Redox Signal. 20, 2361–2371.

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Published In

cover image Antioxidants & Redox Signaling
Antioxidants & Redox Signaling
Volume 20Issue Number 15May 20, 2014
Pages: 2361 - 2371
PubMed: 23758052


Published in print: May 20, 2014
Published online: 30 April 2014
Published ahead of print: 20 July 2013
Published ahead of production: 12 June 2013
Accepted: 11 June 2013
Revision received: 22 May 2013
Received: 30 November 2012


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    Patricia P. Jumbo-Lucioni
    Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia.
    Emily L. Ryan
    Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia.
    Marquise L. Hopson
    Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia.
    Heather M. Bishop
    Summer Undergraduate Research Program at Emory (SURE), Emory University, Atlanta, Georgia.
    Tin Weitner
    Department of Radiation Oncology, Duke University School of Medicine, Durham, North Carolina.
    Artak Tovmasyan
    Department of Radiation Oncology, Duke University School of Medicine, Durham, North Carolina.
    Ivan Spasojevic
    Department of Medicine, Duke University School of Medicine, Durham, North Carolina.
    Ines Batinic-Haberle
    Department of Radiation Oncology, Duke University School of Medicine, Durham, North Carolina.
    Yongliang Liang
    Pulmonary Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.
    Dean P. Jones
    Pulmonary Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.
    Judith L. Fridovich-Keil
    Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia.


    Address correspondence to:Dr. Judith L. Fridovich-KeilDepartment of Human GeneticsEmory University School of MedicineRoom 325.2, Whitehead Building615 Michael StreetAtlanta, GA 30322E-mail: [email protected]

    Author Disclosure Statement

    Both Drs. Batinic-Haberle and Spasojevic are consultants for BioMimetix Pharmaceutical, Inc., Duke University and Drs. Batinic-Haberle and Spasojevic also have patent rights and have licensed technology to BioMimetix Pharmaceutical, Inc., related to this technology.
    All other coauthors have nothing to disclose.

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