The concentration-dependent effects of ethanol on Caenorhabditis elegans behaviour

Mitchell, Philippa; Bull, Kate; Glautier, Steven; Hopper, Neil A.; Holden‐Dye, Lindy; O’Connor, Vincent

doi:10.1038/sj.tpj.6500440

Cited by 56 publications

(70 citation statements)

References 26 publications

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“…This observation is in accordance with previous studies, which described the phenomenon of a concentration-dependent effect in general, 52,53 and in particular for IL-8. 54,55 IL-8 and its receptors, CXCR1 and CXCR2, have been described on endothelial cells 56,57 and have been shown to have a role in endothelial cell proliferation.…”

supporting

confidence: 94%

Regulation of soluble VEGFR-2 secreted by microvascular endothelial cells derived from human BPH

Aweimer

Stachon

Tannapfel

et al. 2011

Prostate Cancer Prostatic Dis

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BACKGROUND: Recently, it was reported that the soluble vascular endothelial growth factor receptor-2 (sVEGFR-2) is secreted by microvascular endothelial cells from human BPH (HPECs). The purpose of this study was to investigate the modulation of sVEGFR-2 by common endothelial cell stimulators. In addition, the physiological role of sVEGFR-2 with regard to the VEGF-stimulated proliferation of HPEC was investigated. METHODS:HPECs were isolated and cultured from fresh BPH tissue. After the incubation of HPECs either with adenosine triphosphate (ATP), interleukin (IL)-6, IL-8 or IL-12, the secretion of sVEGFR-2 was measured by enzyme-linked immunosorbent assay. For measurement of HPEC proliferation influenced by sVEGFR-2, VEGF-stimulated HPEC was cultured with/without sVEGFR-2. Cell proliferation was assessed with the Alamar Blue method. RESULTS:The sVEGFR-2 secretion was increased by ATP and decreased by IL-12 and IL-8, respectively. IL-6 did not show any significant effect on sVEGFR-2 secretion of HPECs. HPEC proliferation was significantly inhibited by sVEGFR-2. CONCLUSIONS:In this study, our data suggest that the secretion of sVEGFR-2 by microvascular endothelial cells from prostate origin is influenced by multiple endothelial cell stimulators. Furthermore, our data suggest that sVEGFR-2 acts as an antiangiogenic factor.

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supporting

confidence: 94%

Regulation of soluble VEGFR-2 secreted by microvascular endothelial cells derived from human BPH

Aweimer

Stachon

Tannapfel

et al. 2011

Prostate Cancer Prostatic Dis

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“…NGM plates were modified with vehicle (0.5% ethanol) or emodepside as described previously . Emodepside modified plates contained drug in concentrations of 10 nM, 100 nM, 1 M, and 10 M. The maximum calculated concentration of ethanol was 86 mM, a concentration that does not exhibit inhibitory effects on the locomotion of C. elegans (Mitchell et al, 2007). Vehicle controls were performed for all experiments.…”

Section: Methodsmentioning

confidence: 99%

Selective Toxicity of the Anthelmintic Emodepside Revealed by Heterologous Expression of Human KCNMA1 inCaenorhabditis elegans

Crisford¹,

Murray²,

O’Connor³

et al. 2011

Mol Pharmacol

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Emodepside is a resistance-breaking anthelmintic of a new chemical class, the cyclooctadepsipeptides. A major determinant of its anthelmintic effect is the calcium-activated potassium channel SLO-1. SLO-1 belongs to a family of channels that are highly conserved across the animal phyla and regulate neurosecretion, hormone release, muscle contraction, and neuronal network excitability. To investigate the selective toxicity of emodepside, we performed transgenic experiments in which the nematode SLO-1 channel was swapped for a mammalian ortholog, human KCNMA1. Expression of either the human channel or Caenorhabditis elegans slo-1 from the native slo-1 promoter in a C. elegans slo-1 functional null mutant rescued behavioral deficits that otherwise resulted from loss of slo-1 signaling. However, worms expressing the human channel were 10-to 100-fold less sensitive to emodepside than those expressing the nematode channel. Strains expressing the human KCNMA1 channel were preferentially sensitive to the mammalian channel agonists NS1619 and rottlerin. In the C. elegans pharyngeal nervous system, slo-1 is expressed in neurons, not muscle, and cell-specific rescue experiments have previously shown that emodepside inhibits serotonin-stimulated feeding by interfering with SLO-1 signaling in the nervous system. Here we show that ectopic overexpression of slo-1 in pharyngeal muscle confers sensitivity of the muscle to emodepside, consistent with a direct interaction of emodepside with the channel. Taken together, these data predict an emodepside-selective pharmacophore harbored by SLO-1. This has implications for the development of this drug/ target interface for the treatment of helminth infections.

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“…38 It is clear that microfluidic trapping did not compromise the regular activity of larval zebrafish, suggesting that our system is valid and convenient for experimental analysis. After loading into the chip, the larvae (7dpf) were treated with ethanol of different concentrations (from 0.00% to 3.00% v/v), 6,28 and their behavioral responses were recorded for 10 min (Figs. 3(a) and 3(b)).…”

Section: Ethanol-induced Behavioral Responses Of Zebrafishmentioning

confidence: 99%

“…In the past, great efforts have been made to study ethanol-induced responses in different animals' models, including C. elegans, 6 drosophila, 7 zebrafish, 8 and rodent animals. 9 Among these models, zebrafish is the only transparent vertebrate with complex organ systems that can be optically accessed in parallel for investigations of physiology in different organs.…”

Section: Introductionmentioning

confidence: 99%

Autonomous system for cross-organ investigation of ethanol-induced acute response in behaving larval zebrafish

Lin

Chen

et al. 2016

Biomicrofluidics

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Ethanol is widely consumed and has been associated with various diseases in different organs. It is therefore important to study ethanol-induced responses in living organisms with the capability to address specific organs in an integrative manner. Here, we developed an autonomous system based on a series of microfluidic chips for cross-organ investigation of ethanol-induced acute response in behaving larval zebrafish. This system enabled high-throughput, gel-free, and anesthetic-free manipulation of larvae, and thus allowed real-time observation of behavioral responses, and associated physiological changes at cellular resolution within specific organs in response to acute ethanol stimuli, which would otherwise be impossible by using traditional methods for larva immobilization and orientation. Specifically, three types of chips ("motion," "lateral," and "dorsal"), based on a simple hydrodynamic design, were used to perform analysis in animal behavior, cardiac, and brain physiology, respectively. We found that ethanol affected larval zebrafish in a dose-dependent manner. The motor function of different body parts was significantly modulated by ethanol treatment, especially at a high dose of 3%. These behavioral changes were temporally associated with a slow-down of heart-beating and a stereotyped activation of certain brain regions. As we demonstrated in this proof-of-concept study, this versatile Fish-on-Chip platform could potentially be adopted for systematic cross-organ investigations involving chemical or genetic manipulations in zebrafish model. Published by AIP Publishing. [http://dx

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The concentration-dependent effects of ethanol on Caenorhabditis elegans behaviour

Cited by 56 publications

References 26 publications

Regulation of soluble VEGFR-2 secreted by microvascular endothelial cells derived from human BPH

Regulation of soluble VEGFR-2 secreted by microvascular endothelial cells derived from human BPH

Selective Toxicity of the Anthelmintic Emodepside Revealed by Heterologous Expression of Human KCNMA1 inCaenorhabditis elegans

Autonomous system for cross-organ investigation of ethanol-induced acute response in behaving larval zebrafish

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