Paraquat administration in Drosophila for use in metabolic studies of oxidative stress

Rzezniczak, Teresa Z.; Douglas, Leisa Antoinette; Watterson, James H.; Merritt, Thomas J.S.

doi:10.1016/j.ab.2011.08.023

Cited by 78 publications

(61 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Interestingly, we did not detect a difference in DA cell death at 4 weeks, which we estimate to be similar to late middle age in humans (Grotewiel et al, 2005, Simon et al, 2006). Prior studies of paraquat exposure in flies show DA cell loss with relatively high doses of paraquat administered in sucrose (Chaudhuri et al, 2007, Lawal et al, 2010); however, in this paradigm flies die within four days of exposure and sucrose itself may be toxic under these conditions (Rzezniczak et al, 2011). Importantly, pathological changes in PD patients usually manifest decades after exposure to high dose pesticide (Goldman, 2014).…”

Section: Discussionmentioning

confidence: 83%

“…Thus, neither current fly nor rodent models replicate the chronic time course of exposure seen in many patient populations (Costello et al, 2009). Moreover, most if not all Drosophila studies of acute paraquat exposure have utilized sucrose as a vehicle (Chaudhuri et al, 2007, Humphreys et al, 1993, Legan et al, 2008), which may increase both oxidative stress and mortality in the fly (Rzezniczak et al, 2011). …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Synergistic effects on dopamine cell death in a Drosophila model of chronic toxin exposure

et al. 2014

View full text Add to dashboard Cite

The neurodegenerative effects of Parkinson’s disease (PD) are marked by a selective loss of dopaminergic (DA) neurons. Epidemiological studies suggest that chronic exposure to the pesticide paraquat may increase the risk for PD and DA cell loss. However, combined exposure with additional fungicide(s) including maneb and/or ziram may be required for pathogenesis. To explore potential pathogenic mechanisms, we have developed a Drosophila model of chronic paraquat exposure. We find that while chronic paraquat exposure alone decreased organismal survival and motor function, combined chronic exposure to both paraquat and maneb was required for DA cell death in the fly. To initiate mechanistic studies of this interaction, we used additional genetic reagents to target the ubiquitin proteasome system, implicated in some rare familial forms of PD and the toxic effects of ziram. Genetic inhibition of E1 ubiquitin ligase, but not the proteasome itself, increased DA cell death in combination with maneb but not paraquat. These studies establish a model for long-term exposure to multiple pesticides, and support the idea that pesticide interactions relevant to PD may involve inhibition of protein ubiquitination.

show abstract

Section: Discussionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Synergistic effects on dopamine cell death in a Drosophila model of chronic toxin exposure

et al. 2014

View full text Add to dashboard Cite

show abstract

“…In Drosophila, foodborne paraquat exposure is the standard assay for testing oxidative stress resistance (Rzezniczak et al 2011;Sun et al 2013) and many fly studies successfully used this single agent (e.g., Alic et al 2011;Barnes et al 2014;Lin et al 2014). Following this protocol, we observed increased paraquat resistance in all tested mutants deficient in AKH signaling.…”

Section: Roles Of Akh Signaling In Oxidative Stress Resistancementioning

confidence: 87%

“…However, the AKH titer positively correlated with oxidative stress induced by bacterial toxin in Leptinotarsa decemlineata , and by paraquat in P. apterus (Večeřa et al 2007) and L. decemlineata ). Moreover, co-injection of AKH alleviated the effect of paraquat by enhancing the antioxidative capacity in the firebug (Večeřa et al 2007), suggesting a protective role of AKH during oxidative stress response.In Drosophila, foodborne paraquat exposure is the standard assay for testing oxidative stress resistance (Rzezniczak et al 2011;Sun et al 2013) and many fly studies successfully used this single agent (e.g., Alic et al 2011;Barnes et al 2014;Lin et al 2014). Following this protocol, we observed increased paraquat resistance in all tested mutants deficient in AKH signaling.…”

mentioning

confidence: 87%

Energy Homeostasis Control in Drosophila Adipokinetic Hormone Mutants

et al. 2015

View full text Add to dashboard Cite

Maintenance of biological functions under negative energy balance depends on mobilization of storage lipids and carbohydrates in animals. In mammals, glucagon and glucocorticoid signaling mobilizes energy reserves, whereas adipokinetic hormones (AKHs) play a homologous role in insects. Numerous studies based on AKH injections and correlative studies in a broad range of insect species established the view that AKH acts as master regulator of energy mobilization during development, reproduction, and stress. In contrast to AKH, the second peptide, which is processed from the Akh encoded prohormone [termed "adipokinetic hormone precursor-related peptide" (APRP)] is functionally orphan. APRP is discussed as ecdysiotropic hormone or as scaffold peptide during AKH prohormone processing. However, as in the case of AKH, final evidence for APRP functions requires genetic mutant analysis. Here we employed CRISPR/Cas9-mediated genome engineering to create AKH and AKH plus APRP-specific mutants in the model insect Drosophila melanogaster. Lack of APRP did not affect any of the tested steroid-dependent processes. Similarly, Drosophila AKH signaling is dispensable for ontogenesis, locomotion, oogenesis, and homeostasis of lipid or carbohydrate storage until up to the end of metamorphosis. During adulthood, however, AKH regulates body fat content and the hemolymph sugar level as well as nutritional and oxidative stress responses. Finally, we provide evidence for a negative autoregulatory loop in Akh gene regulation.KEYWORDS Drosophila; adipokinetic hormone; adipokinetic hormone precursor-related peptide; energy homeostasis; stress resistance E NERGY homeostasis requires continuous compensation for fluctuations in the energy expenditure and availability of food resources. Organisms thus build up reserves under positive energy balance and catabolize them when the balance turns negative to retain stable levels of circulating energy fuel. Insulin signaling induces the uptake of excessive circulating sugars, thus promoting reserve accumulation (reviewed, e.g., in Saltiel and Kahn 2001; Cohen 2006), whereas energy mobilization is under the control of glucagon and glucocorticoid signaling in mammals (reviewed, e.g., in Rui 2014;Charron and Vuguin 2015) and adipokinetic hormone (AKH) signaling in insects (reviewed, e.g., in Van der Horst 2003;Lorenz and Gäde 2009;Bednářová et al. 2013a). Consistent with their fundamental physiological function in energy mobilization, AKHs are found not only in insects, but are common in Protostomia, where they have been identified both in Ecdyszoa (in Arthropoda, Tardigrada, and Priapulida) and Lophotrochozoa (in Mollusca, Rotifera, and Annelida) (Gäde 2009;Hauser and Grimmelikhuijzen 2014). Nevertheless, physiological functions of AKHs have been studied mainly in Arthropoda. Similar to mammals, also insects store lipids in the form of triacylglycerides (TGs) and as carbohydrates in the form of glycogen. The main storage organ for lipid and glycogen in insects is the fat body, which can thus b...

show abstract

“…In the present study, D. melanogaster was exposed orally to C. campestris hydroalcoholic extract. Its consumption by the fly caused toxicity, and increased the effect of PQ that has been extensively used as a model of OS in D. melanogaster (Rzezniczak et al 2011), leading to reduction in lifespan, likely due to the damage mediated by ROS to proteins, lipids and DNA (Finkel & Holbrook 2000). We evaluated by HPLC the presence of flavonoids, tannins and phenolic acids.…”

Section: Discussionmentioning

confidence: 99%

Oxidant effects and toxicity of Croton campestris in Drosophila melanogaster

Júnior

Macedo

Zemolin

et al. 2016

Pharmaceutical Biology

View full text Add to dashboard Cite

Context: Croton campestris A.St.-Hil. (Euphorbiaceae) is a species native to Northeast Brazil used by traditional communities for the treatment of a variety of health problems. However, potential toxicological effects of this plant are unknown. Objective: The potential toxicity of the hydroalcoholic extract of C. campestris leaves on Drosophila melanogaster insect model, additionally with phytochemical constitution and cellular mechanisms mediating the action of extract were analysed in this study. Materials and methods: Constituents of the extract were evaluated by HPLC. In vitro antioxidant potential of extract was analysed by DPPH, ABTS and FRAP. Flies injected culture medium mixed with extract (0.1-50 mg/mL) for 72 h. After, ROS production was evaluated by DCF-DA oxidation. Phosphorylation of MAPK signalling pathway was investigated by Western blotting method. Activity of antioxidant enzymes was analysed in homogenates.Results: Major components of the extract include quercetin (38.11 ± 0.06 mg/g), caffeic acid (20.06 ± 0.17 mg/g) and kaempferol (15.45 ± 0.05 mg/g). Consumption of the extract impaired locomotor performance and induced fly death of flies (LC 50 of 26.51 mg/mL). Augmented ROS formation and SOD, CAT and GST activity were observed from 0.1 mg/mL. JNK and p38 kinases phosphorylation was modulated and Paraquat-induced toxicity was augmented by extract. Discussion and conclusion: Our data show important toxicological effects of C. campestris leading to increased mortality and impaired locomotor performance accompanied by induction of cell stress markers in flies. The study draws attention to the indiscriminate use of plant extracts. ARTICLE HISTORY

show abstract

Paraquat administration in Drosophila for use in metabolic studies of oxidative stress

Cited by 78 publications

References 13 publications

Synergistic effects on dopamine cell death in a Drosophila model of chronic toxin exposure

Synergistic effects on dopamine cell death in a Drosophila model of chronic toxin exposure

Energy Homeostasis Control in Drosophila Adipokinetic Hormone Mutants

Oxidant effects and toxicity of Croton campestris in Drosophila melanogaster

Contact Info

Product

Resources

About