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Presenilin promotes dietary copper uptake.

Southon A, Greenough MA, Ganio G, Bush AI, Burke R, Camakaris J - PLoS ONE (2013)

Bottom Line: Expression of a copper-responsive EYFP construct was also lower in the midgut of these larvae, indicative of reduced dietary copper uptake.SOD activity was reduced by midgut PSN knockdown, and these flies were sensitive to the superoxide-inducing chemical paraquat.These results are consistent with previous studies of mammalian presenilins, supporting a conserved role for these proteins in mediating copper uptake.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, The University of Melbourne, Victoria, Australia.

ABSTRACT
Dietary copper is essential for multicellular organisms. Copper is redox active and required as a cofactor for enzymes such as the antioxidant Superoxide Dismutase 1 (SOD1). Copper dyshomeostasis has been implicated in Alzheimer's disease. Mutations in the presenilin genes encoding PS1 and PS2 are major causes of early-onset familial Alzheimer's disease. PS1 and PS2 are required for efficient copper uptake in mammalian systems. Here we demonstrate a conserved role for presenilin in dietary copper uptake in the fly Drosophila melanogaster. Ubiquitous RNA interference-mediated knockdown of the single Drosophila presenilin (PSN) gene is lethal. However, PSN knockdown in the midgut produces viable flies. These flies have reduced copper levels and are more tolerant to excess dietary copper. Expression of a copper-responsive EYFP construct was also lower in the midgut of these larvae, indicative of reduced dietary copper uptake. SOD activity was reduced by midgut PSN knockdown, and these flies were sensitive to the superoxide-inducing chemical paraquat. These data support presenilin being needed for dietary copper uptake in the gut and so impacting on SOD activity and tolerance to oxidative stress. These results are consistent with previous studies of mammalian presenilins, supporting a conserved role for these proteins in mediating copper uptake.

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Related in: MedlinePlus

Metal tolerance in Drosophila.Copper tolerance (A) and zinc tolerance (B) were assessed by survival to adulthood on basal media and metal-supplemented media for control (RNAi control, GAL4 control) and midgut PSN knockdown (PSN RNAi) Drosophila. Values are percentage survival with S.E.M. from fifteen replicates of 50 Drosophila. PSN knockdown Drosophila were highly tolerant to copper-supplemented media. aSignificant difference from RNAi control, bsignificant difference from GAL4 control, as determined by two-way ANOVA with Tukey’s post-hoc test (P<0.05).
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pone-0062811-g001: Metal tolerance in Drosophila.Copper tolerance (A) and zinc tolerance (B) were assessed by survival to adulthood on basal media and metal-supplemented media for control (RNAi control, GAL4 control) and midgut PSN knockdown (PSN RNAi) Drosophila. Values are percentage survival with S.E.M. from fifteen replicates of 50 Drosophila. PSN knockdown Drosophila were highly tolerant to copper-supplemented media. aSignificant difference from RNAi control, bsignificant difference from GAL4 control, as determined by two-way ANOVA with Tukey’s post-hoc test (P<0.05).

Mentions: Metal tolerance was examined in Drosophila reared on basal media and media supplemented with additional copper (Figure 1A) and zinc (Figure 1B). w1118 control flies were crossed to both the PSN-RNAi stock and the MEX-GAL4 stock to create two control strains referred to as RNAi control and GAL4 control, respectively. Midgut PSN knockdown did not alter survival on basal media relative to either control strain, indicating the reduction in PSN levels did not have a major fitness cost. Survival on copper-supplemented media was much greater in the PSN knockdown flies (Figure 1A). This was significant relative to both controls and only PSN knockdown flies survived the highest copper concentration. Rearing PSN knockdown flies on media supplemented with the copper-chelator BCS did not significantly affect their survival (Figure S1). Survival on zinc-supplemented media was not consistently different between midgut PSN knockdown flies and controls (Figure 1B).


Presenilin promotes dietary copper uptake.

Southon A, Greenough MA, Ganio G, Bush AI, Burke R, Camakaris J - PLoS ONE (2013)

Metal tolerance in Drosophila.Copper tolerance (A) and zinc tolerance (B) were assessed by survival to adulthood on basal media and metal-supplemented media for control (RNAi control, GAL4 control) and midgut PSN knockdown (PSN RNAi) Drosophila. Values are percentage survival with S.E.M. from fifteen replicates of 50 Drosophila. PSN knockdown Drosophila were highly tolerant to copper-supplemented media. aSignificant difference from RNAi control, bsignificant difference from GAL4 control, as determined by two-way ANOVA with Tukey’s post-hoc test (P<0.05).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3646984&req=5

pone-0062811-g001: Metal tolerance in Drosophila.Copper tolerance (A) and zinc tolerance (B) were assessed by survival to adulthood on basal media and metal-supplemented media for control (RNAi control, GAL4 control) and midgut PSN knockdown (PSN RNAi) Drosophila. Values are percentage survival with S.E.M. from fifteen replicates of 50 Drosophila. PSN knockdown Drosophila were highly tolerant to copper-supplemented media. aSignificant difference from RNAi control, bsignificant difference from GAL4 control, as determined by two-way ANOVA with Tukey’s post-hoc test (P<0.05).
Mentions: Metal tolerance was examined in Drosophila reared on basal media and media supplemented with additional copper (Figure 1A) and zinc (Figure 1B). w1118 control flies were crossed to both the PSN-RNAi stock and the MEX-GAL4 stock to create two control strains referred to as RNAi control and GAL4 control, respectively. Midgut PSN knockdown did not alter survival on basal media relative to either control strain, indicating the reduction in PSN levels did not have a major fitness cost. Survival on copper-supplemented media was much greater in the PSN knockdown flies (Figure 1A). This was significant relative to both controls and only PSN knockdown flies survived the highest copper concentration. Rearing PSN knockdown flies on media supplemented with the copper-chelator BCS did not significantly affect their survival (Figure S1). Survival on zinc-supplemented media was not consistently different between midgut PSN knockdown flies and controls (Figure 1B).

Bottom Line: Expression of a copper-responsive EYFP construct was also lower in the midgut of these larvae, indicative of reduced dietary copper uptake.SOD activity was reduced by midgut PSN knockdown, and these flies were sensitive to the superoxide-inducing chemical paraquat.These results are consistent with previous studies of mammalian presenilins, supporting a conserved role for these proteins in mediating copper uptake.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, The University of Melbourne, Victoria, Australia.

ABSTRACT
Dietary copper is essential for multicellular organisms. Copper is redox active and required as a cofactor for enzymes such as the antioxidant Superoxide Dismutase 1 (SOD1). Copper dyshomeostasis has been implicated in Alzheimer's disease. Mutations in the presenilin genes encoding PS1 and PS2 are major causes of early-onset familial Alzheimer's disease. PS1 and PS2 are required for efficient copper uptake in mammalian systems. Here we demonstrate a conserved role for presenilin in dietary copper uptake in the fly Drosophila melanogaster. Ubiquitous RNA interference-mediated knockdown of the single Drosophila presenilin (PSN) gene is lethal. However, PSN knockdown in the midgut produces viable flies. These flies have reduced copper levels and are more tolerant to excess dietary copper. Expression of a copper-responsive EYFP construct was also lower in the midgut of these larvae, indicative of reduced dietary copper uptake. SOD activity was reduced by midgut PSN knockdown, and these flies were sensitive to the superoxide-inducing chemical paraquat. These data support presenilin being needed for dietary copper uptake in the gut and so impacting on SOD activity and tolerance to oxidative stress. These results are consistent with previous studies of mammalian presenilins, supporting a conserved role for these proteins in mediating copper uptake.

Show MeSH
Related in: MedlinePlus