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Insulin production and signaling in renal tubules of Drosophila is under control of tachykinin-related peptide and regulates stress resistance.

Söderberg JA, Birse RT, Nässel DR - PLoS ONE (2011)

Bottom Line: Targeted knockdown of DTKR, DILP5 and the insulin receptor dInR in principal cells or mutation of Dilp5 resulted in increased survival at either stress, whereas over-expression of these components produced the opposite phenotype.Manipulations of S6 kinase and superoxide dismutase (SOD2) in principal cells also affect survival at stress, suggesting that DILP5 acts locally on tubules, possibly in oxidative stress regulation.Our findings are the first to demonstrate DILP signaling originating in the renal tubules and that this signaling is under control of stress-induced release of peptide hormone.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, Stockholm University, Stockholm, Sweden.

ABSTRACT
The insulin-signaling pathway is evolutionarily conserved in animals and regulates growth, reproduction, metabolic homeostasis, stress resistance and life span. In Drosophila seven insulin-like peptides (DILP1-7) are known, some of which are produced in the brain, others in fat body or intestine. Here we show that DILP5 is expressed in principal cells of the renal tubules of Drosophila and affects survival at stress. Renal (Malpighian) tubules regulate water and ion homeostasis, but also play roles in immune responses and oxidative stress. We investigated the control of DILP5 signaling in the renal tubules by Drosophila tachykinin peptide (DTK) and its receptor DTKR during desiccative, nutritional and oxidative stress. The DILP5 levels in principal cells of the tubules are affected by stress and manipulations of DTKR expression in the same cells. Targeted knockdown of DTKR, DILP5 and the insulin receptor dInR in principal cells or mutation of Dilp5 resulted in increased survival at either stress, whereas over-expression of these components produced the opposite phenotype. Thus, stress seems to induce hormonal release of DTK that acts on the renal tubules to regulate DILP5 signaling. Manipulations of S6 kinase and superoxide dismutase (SOD2) in principal cells also affect survival at stress, suggesting that DILP5 acts locally on tubules, possibly in oxidative stress regulation. Our findings are the first to demonstrate DILP signaling originating in the renal tubules and that this signaling is under control of stress-induced release of peptide hormone.

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Knockdown of superoxide dismutase in renal tubules diminishes survival during stress.A. Knock-down of mitochondrial manganese superoxide dismutase (MnSOD; SOD2) in principal cells (C324/MnSOD-RNAi) and exposure of flies to desiccation reduced lifespan significantly (P<0.001 to both parental controls; Log rank test; n = 64–96 for the different genotypes). B. Knockdown of cytoplasmic CuZnSOD (SOD1) in principal cells (C324/SOD1-RNAi) did not produce a strong phenotype at desiccation (P<0.01 compared to SOD1-RNAi/w1118 and P = 0.1 to C324/w1118; n = 64–92 for the different genotypes).
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pone-0019866-g007: Knockdown of superoxide dismutase in renal tubules diminishes survival during stress.A. Knock-down of mitochondrial manganese superoxide dismutase (MnSOD; SOD2) in principal cells (C324/MnSOD-RNAi) and exposure of flies to desiccation reduced lifespan significantly (P<0.001 to both parental controls; Log rank test; n = 64–96 for the different genotypes). B. Knockdown of cytoplasmic CuZnSOD (SOD1) in principal cells (C324/SOD1-RNAi) did not produce a strong phenotype at desiccation (P<0.01 compared to SOD1-RNAi/w1118 and P = 0.1 to C324/w1118; n = 64–92 for the different genotypes).

Mentions: Oxidative stress is a major factor in the process of aging [49], [50]. Renal tubules are known to be involved in responses to oxidative stress [29], [51]. In fact, knock down of a mitochondrial inner membrane ATP/ADP exchanger, ANT, in principal cells of renal tubules is sufficient to reduce survival of the fly at oxidative stress [29]. Mitochondrial respiration is a major source of reactive oxygen species and one defense against oxidative stress is superoxide dismutase 2 (SOD2; MnSOD) located in mitochondria [52]. Transcript of Sod2 (CG8905) is enriched in adult renal tubules (FlyAtlas) and therefore tested the effects of knocking down Sod2 in principal cells on survival at desiccation. Flies with the transgenes C324/sod2-RNAi displayed significantly reduced lifespan at desiccation (Fig. 7A; P<0.001). We also crossed C324 flies to UAS-Sod1-RNAi to test whether the cytoplasmic CuZnSOD (SOD1, CG11793) plays a role in the principal cells. Flies of this cross did not differ from controls in their response to desiccation (Fig. 7B; P = 0.1), in congruence with FlyAtlas data showing no enrichment of Sod1 transcript in renal tubules. At present we have no evidence that DILP signaling affects SOD2 activity, although knockdown of both in principal cells affect survival at desiccation.


Insulin production and signaling in renal tubules of Drosophila is under control of tachykinin-related peptide and regulates stress resistance.

Söderberg JA, Birse RT, Nässel DR - PLoS ONE (2011)

Knockdown of superoxide dismutase in renal tubules diminishes survival during stress.A. Knock-down of mitochondrial manganese superoxide dismutase (MnSOD; SOD2) in principal cells (C324/MnSOD-RNAi) and exposure of flies to desiccation reduced lifespan significantly (P<0.001 to both parental controls; Log rank test; n = 64–96 for the different genotypes). B. Knockdown of cytoplasmic CuZnSOD (SOD1) in principal cells (C324/SOD1-RNAi) did not produce a strong phenotype at desiccation (P<0.01 compared to SOD1-RNAi/w1118 and P = 0.1 to C324/w1118; n = 64–92 for the different genotypes).
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3091884&req=5

pone-0019866-g007: Knockdown of superoxide dismutase in renal tubules diminishes survival during stress.A. Knock-down of mitochondrial manganese superoxide dismutase (MnSOD; SOD2) in principal cells (C324/MnSOD-RNAi) and exposure of flies to desiccation reduced lifespan significantly (P<0.001 to both parental controls; Log rank test; n = 64–96 for the different genotypes). B. Knockdown of cytoplasmic CuZnSOD (SOD1) in principal cells (C324/SOD1-RNAi) did not produce a strong phenotype at desiccation (P<0.01 compared to SOD1-RNAi/w1118 and P = 0.1 to C324/w1118; n = 64–92 for the different genotypes).
Mentions: Oxidative stress is a major factor in the process of aging [49], [50]. Renal tubules are known to be involved in responses to oxidative stress [29], [51]. In fact, knock down of a mitochondrial inner membrane ATP/ADP exchanger, ANT, in principal cells of renal tubules is sufficient to reduce survival of the fly at oxidative stress [29]. Mitochondrial respiration is a major source of reactive oxygen species and one defense against oxidative stress is superoxide dismutase 2 (SOD2; MnSOD) located in mitochondria [52]. Transcript of Sod2 (CG8905) is enriched in adult renal tubules (FlyAtlas) and therefore tested the effects of knocking down Sod2 in principal cells on survival at desiccation. Flies with the transgenes C324/sod2-RNAi displayed significantly reduced lifespan at desiccation (Fig. 7A; P<0.001). We also crossed C324 flies to UAS-Sod1-RNAi to test whether the cytoplasmic CuZnSOD (SOD1, CG11793) plays a role in the principal cells. Flies of this cross did not differ from controls in their response to desiccation (Fig. 7B; P = 0.1), in congruence with FlyAtlas data showing no enrichment of Sod1 transcript in renal tubules. At present we have no evidence that DILP signaling affects SOD2 activity, although knockdown of both in principal cells affect survival at desiccation.

Bottom Line: Targeted knockdown of DTKR, DILP5 and the insulin receptor dInR in principal cells or mutation of Dilp5 resulted in increased survival at either stress, whereas over-expression of these components produced the opposite phenotype.Manipulations of S6 kinase and superoxide dismutase (SOD2) in principal cells also affect survival at stress, suggesting that DILP5 acts locally on tubules, possibly in oxidative stress regulation.Our findings are the first to demonstrate DILP signaling originating in the renal tubules and that this signaling is under control of stress-induced release of peptide hormone.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, Stockholm University, Stockholm, Sweden.

ABSTRACT
The insulin-signaling pathway is evolutionarily conserved in animals and regulates growth, reproduction, metabolic homeostasis, stress resistance and life span. In Drosophila seven insulin-like peptides (DILP1-7) are known, some of which are produced in the brain, others in fat body or intestine. Here we show that DILP5 is expressed in principal cells of the renal tubules of Drosophila and affects survival at stress. Renal (Malpighian) tubules regulate water and ion homeostasis, but also play roles in immune responses and oxidative stress. We investigated the control of DILP5 signaling in the renal tubules by Drosophila tachykinin peptide (DTK) and its receptor DTKR during desiccative, nutritional and oxidative stress. The DILP5 levels in principal cells of the tubules are affected by stress and manipulations of DTKR expression in the same cells. Targeted knockdown of DTKR, DILP5 and the insulin receptor dInR in principal cells or mutation of Dilp5 resulted in increased survival at either stress, whereas over-expression of these components produced the opposite phenotype. Thus, stress seems to induce hormonal release of DTK that acts on the renal tubules to regulate DILP5 signaling. Manipulations of S6 kinase and superoxide dismutase (SOD2) in principal cells also affect survival at stress, suggesting that DILP5 acts locally on tubules, possibly in oxidative stress regulation. Our findings are the first to demonstrate DILP signaling originating in the renal tubules and that this signaling is under control of stress-induced release of peptide hormone.

Show MeSH
Related in: MedlinePlus