18 research outputs found
Hormonal signaling in cnidarians : do we understand the pathways well enough to know whether they are being disrupted?
Author Posting. © The Author, 2006. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Ecotoxicology 16 (2007): 5-13, doi:10.1007/s10646-006-0121-1.Cnidarians occupy a key evolutionary position as basal metazoans and are ecologically
important as predators, prey and structure-builders. Bioregulatory molecules (e.g.,
amines, peptides and steroids) have been identified in cnidarians, but cnidarian signaling
pathways remain poorly characterized. Cnidarians, especially hydras, are regularly used
in toxicity testing, but few studies have used cnidarians in explicit testing for signal
disruption. Sublethal endpoints developed in cnidarians include budding, regeneration,
gametogenesis, mucus production and larval metamorphosis. Cnidarian genomic
databases, microarrays and other molecular tools are increasingly facilitating mechanistic
investigation of signaling pathways and signal disruption. Elucidation of cnidarian
signaling processes in a comparative context can provide insight into the evolution and
diversification of metazoan bioregulation. Characterizing signaling and signal disruption
in cnidarians may also provide unique opportunities for evaluating risk to valuable
marine resources, such as coral reefs
Environmental sensing and response genes in cnidaria : the chemical defensome in the sea anemone Nematostella vectensis
Author Posting. © The Author(s), 2008. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Cell Biology and Toxicology 24 (2008): 483-502, doi:10.1007/s10565-008-9107-5.The starlet sea anemone Nematostella vectensis has been recently established as a
new model system for the study of the evolution of developmental processes, as cnidaria
occupy a key evolutionary position at the base of the bilateria. Cnidaria play important
roles in estuarine and reef communities, but are exposed to many environmental stressors.
Here I describe the genetic components of a ‘chemical defensome’ in the genome of
N. vectensis, and review cnidarian molecular toxicology. Gene families that defend
against chemical stressors and the transcription factors that regulate these genes have
been termed a ‘chemical defensome,’ and include the cytochromes P450 and other
oxidases, various conjugating enyzymes, the ATP-dependent efflux transporters,
oxidative detoxification proteins, as well as various transcription factors. These genes
account for about 1% (266/27200) of the predicted genes in the sea anemone genome,
similar to the proportion observed in tunicates and humans, but lower than that observed
in sea urchins. While there are comparable numbers of stress-response genes, the stress
sensor genes appear to be reduced in N. vectensis relative to many model protostomes
and deuterostomes. Cnidarian toxicology is understudied, especially given the important
ecological roles of many cnidarian species. New genomic resources should stimulate the
study of chemical stress sensing and response mechanisms in cnidaria, and allow us to
further illuminate the evolution of chemical defense gene networks.WHOI Ocean Life Institute and NIH R01-ES01591
Folia2.qxp
Abstract. Valproic acid (2-propyl pentanoic acid) is a drug used for the treatment of epilepsy and bipolar disorder. Although very rare, side effects such as spina bifida and other defects of neural tube closure indicate that valproic acid interferes with developmental regulatory pathways. Recently obtained data show that valproic acid affects cell growth, differentiation, apoptosis and immunogenicity of cultured cancer cells and tumours. Focused studies uncovered the potential of valproic acid to interfere with multiple regulatory mechanisms including histone deacetylases, GSK3 α α and β β, Akt, the ERK pathway, the phosphoinositol pathway, the tricarboxylic acid cycle, GABA, and the OXPHOS system. Valproic acid is emerging as a potential anticancer drug and may also serve as a molecular lead that can help design drugs with more specific and more potent effects on the one side and drugs with wide additive but weaker effects on the other. Valproic acid is thus a powerful molecular tool for better understanding and therapeutic targeting of pathways that regulate the behaviour of cancer cells
AHR38, a homolog of NGFI–B, inhibits formation of the functional ecdysteroid receptor in the mosquito Aedes aegypti
In anautogenous mosquitoes, vitellogenesis, the key event in egg maturation, requires a blood meal. Consequently, mosquitoes are vectors of numerous devastating human diseases. After ingestion of blood, 20–hydroxyecdysone activates yolk protein precursor (YPP) genes in the metabolic tissue, the fat body. An important adaptation for anautogenicity is the previtellogenic developmental arrest (the state-of-arrest) preventing the activation of YPP genes in previtellogenic females prior to blood feeding. Here, we show that a retinoid X receptor homolog, Ultraspiracle (AaUSP), which is an obligatory partner in the functional ecdysteroid receptor, exists at the state-of-arrest as a heterodimer with the orphan nuclear receptor AHR38, a homolog of Drosophila DHR38 and nerve growth factor-induced protein B. Yeast two-hybrid and glutathione S-transferase pull-down assays demonstrate that AHR38 can interact strongly with AaUSP. AHR38 also disrupts binding of ecdysteroid receptor to ecdysone response elements. Cell co-transfection of AHR38 with AaEcR and AaUSP inhibits ecdysone-dependent activation of a reporter gene by the ecdysteroid receptor. Co-immunoprecipitation experiments indicate that AaUSP protein associates with AHR38 instead of AaEcR in fat body nuclei at the state-of-arrest