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

Autori
Jumbo-Lucioni, Patricia P. ; Ryan, Emily L. ; Hopson, Marquise L. ; Bishop, Heather M. ; Weitner, Tin ; Tovmasyan, Artak ; Spasojevic, Ivan ; Batinic- Haberle, Ines ; Liang, Yongliang ; Jones, Dean P. ; Fridovich-Keil, Judith L. ;

Izvornik
Antioxidants & redox signaling (1523-0864) 20 (2014), 15; 2361-2371

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Superoxide Dismutase Mimics; Manganese Porphyrins; Galactosemia

Sažetak
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. 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. 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.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA