<i>In vitro</i> effects of organophosphorus compounds on calmodulin activity

Pala, I.; Vig, P. J. S.; Desaiah, Durisala; Srinivasan, A.

doi:10.1002/jat.2550110603

Cited by 14 publications

(9 citation statements)

References 20 publications

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“…Furthermore, OP compounds inhibit calmodulin activity and its active conformation (Pala et al, 1991). Jung et al (2003) demonstrated that the N-nitroso metabolite of carbofuran, N-nitrosocarbofuran induces apoptosis in mouse brain microvascular endothelial cells, at least in part through the ERK pathway.…”

Section: Discussionmentioning

confidence: 99%

Carbofuran and malathion inhibit nucleotide hydrolysis in zebrafish (Danio rerio) brain membranes

et al. 2005

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Section: Discussionmentioning

confidence: 99%

Carbofuran and malathion inhibit nucleotide hydrolysis in zebrafish (Danio rerio) brain membranes

et al. 2005

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“…We therefore used N-phenyl-I -naphthylamine, an analogue of this probe, that lacks the sulphonate group and which is more specifically targeted to hydrophobic patches of aFGF exposed upon acidification. This molecule has also been previously used to monitor the enhanced exposure of the hydrophobic cores of proteins generated by conformational changes [33]. The results of the binding of N-phenyl-1-naphthylamine to aFGF, at different that some hydrophobic patches persist in the protein at pH 2.0.…”

Section: N-phenyl-1-naphthylamine Binding Molten Globule Interme-mentioning

confidence: 99%

A partly Folded State of Acidic Fibroblast Growth Factor at Low Ph

Sanz

Giménez‐Gallego

1997

European Journal of Biochemistry

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Acid denaturation of acidic fibroblast growth factor (aFGF) at low ionic strength was monitored by far-ultraviolet circular dichroism and intrinsic fluorescence. The two spectroscopic probes displayed noncoincident transitions, which suggested the accumulation of partly folded species around pH 4.0. Although under these conditions the fluorescence of aFGF resembled that of the unfolded form of the protein, farultraviolet circular dichroism and proton nuclear magnetic resonance spectra indicated the presence of persistent secondary and tertiary structure. Moreover, at pH 4.0, aFGF showed cooperative thermal denaturation and interacted weakly with the hydrophobic probe N-phenyl-1-naphthylamine, showing a relatively high level of structure that did not fit into the classical molten globule category. This intermediate is also capable of interacting with liposomes and might represent a membrane translocation-competent form.Keywords: protein structure ; protein folding ; folding intermediate; translocation across membranes.Acidic and basic fibroblast growth factors (aFGF and bFGF, respectively) are proteins that induce mitogenesis in most mesoderm-and neuroectoderm-derived cell lines, and show many other hormone-like activities. The three-dimensional structures of the two polypeptides have been determined by X-ray diffraction and 'H-NMR [ l , 21. Their folding topology is similar and follows the p-trefoil motif [3]. However, no clear-cut differences in the biological activities between these two proteins have been observed [4-61. Both bind with high affinity to heparin and they are also referred to as heparin-binding growth factors. The interaction with heparin protects FCF proteins against denaturation [4] and is necessary for their binding to transmembrane tyrosine kinase receptors on the membrane to trigger mitogenesis [7, 81. Binding of FGF to their receptors causes tyrosine phosphorylation of several proteins, including the receptor, and translocation of the protein to the cell nucleus [9, 101 where it induces DNA synthesis. The study of the process of FGF translocation is, therefore, of special interest. It has been shown that aFGF fused to diphteria toxin translocates to the cytosol by a mechanism requiring low pH (4.3, and this process is prevented by the presence of heparin, which stabilizes FGF against pH denaturation [11-131. Recently, it has been reported that low pH also induces interaction of aFGF with acidic phospholipid membranes [ 141. Thus, it seems that translocation-competent aFGF has a partially folded structure like that induced by moderately acidic pH conditions. There is ample evidence that Correspondence to J. M. Sanz, Centro de Investigaciones Biologicas Fax: +34 15649075.

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“…For example, the MAL-M exposure significantly altered genes involved in the protein kinase A signaling pathway, which is essential in maintaining olfactory signal transduction, including odor-induced response (Vielma et al, 2008) and axon pathfinding in fish ORNs (Yoshida et al, 2002). In vitro studies have suggested involvement of calcium signaling in MALinduced neurotoxicity, likely via inhibiting calmodulin (CaM) activity (Pala et al, 1991). We observed a down-regulation of CAMK2A, which may also suggest an interference of calcium signaling by MAL exposure.…”

Section: Discussionmentioning

confidence: 60%

Olfactory Transcriptional Analysis of Salmon Exposed to Mixtures of Chlorpyrifos and Malathion Reveal Novel Molecular Pathways of Neurobehavioral Injury

et al. 2015

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Pacific salmon exposed to sublethal concentrations of organophosphate pesticides (OP) have impaired olfactory function that can lead to loss of behaviors that are essential for survival. These exposures often involve mixtures and can occur at levels below those which inhibit acetylcholinesterase (AChE). In this study, juvenile Coho salmon were exposed for 24 h to either 0.1, 0.5, or 2.5 ppb chlorpyrifos (CPF), 2, 10, or 50 ppb malathion (MAL), or binary mixtures of 0.1 CPF:2 ppb MAL, 0.5 CPF:10 ppb MAL, or 2.5 CPF:10 ppb MAL to mimic single and binary environmental exposures. Microarray analysis of olfactory rosettes from pesticide-exposed salmon revealed differentially expressed genes involved in nervous system function and signaling, aryl hydrocarbon receptor signaling, xenobiotic metabolism, and mitochondrial dysfunction. Coho exposed to OP mixtures exhibited a more pronounced loss in detection of a predatory olfactory cue relative to those exposed to single compounds, whereas respirometry experiments demonstrated that exposure to OPs, individually and in mixtures, reduced maximum respiratory capacity of olfactory rosette mitochondria. The observed molecular, biochemical, and behavioral effects occurred largely in the absence of effects on brain AChE. In summary, our results provide new insights associated with the sublethal neurotoxic effects of OP mixtures relevant to environmental exposures involving molecular and cellular pathways of injury to the salmon olfactory system that underlie neurobehavioral injury.

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In vitro effects of organophosphorus compounds on calmodulin activity

Cited by 14 publications

References 20 publications

Carbofuran and malathion inhibit nucleotide hydrolysis in zebrafish (Danio rerio) brain membranes

Carbofuran and malathion inhibit nucleotide hydrolysis in zebrafish (Danio rerio) brain membranes

A partly Folded State of Acidic Fibroblast Growth Factor at Low Ph

Olfactory Transcriptional Analysis of Salmon Exposed to Mixtures of Chlorpyrifos and Malathion Reveal Novel Molecular Pathways of Neurobehavioral Injury

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