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Surfactant-Induced TRPV1 Activity—A Novel Mechanismfor Eye Irritation?
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi. (Anna Forsby)
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi.ORCID-id: 0000-0001-6298-201X
2007 (Engelska)Ingår i: Toxicological Sciences, ISSN 1096-6080, E-ISSN 1096-0929, Vol. 99, nr 1, s. 174-180Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The pain receptor transient receptor potential vanilloid type 1 (TRPV1) has been reported as one of the key components in the pain pathway.  Activation of the receptor causes a Ca2+ influx with secondary effects leading to neurogenic inflammation. Here we report specific activation of TRPV1 by detergent-containing hygiene products measured as intracellular Ca2+ influxes in stably TRPV1-expressing neuroblastoma SH-SY5Y cells. Children products marketed as “painless” (containing lower concentration of detergents), and conditioners (without detergents) did not induce specific TRPV1 activation. Furthermore, low concentrations of the detergent sodium lauryl sulfate (SLS) dose-dependently induced Ca2+ influxes that could be addressed to TRPV1. These results reveal a novel mechanistic pathway for surfactant-induced nociception, which may be an important endpoint in in vitro test batteries as alternatives to Draize’s rabbit eye test for classification of eye irritating products.

Ort, förlag, år, upplaga, sidor
2007. Vol. 99, nr 1, s. 174-180
Identifikatorer
URN: urn:nbn:se:su:diva-30178DOI: 10.1093/toxsci/kfm164ISI: 000249148300018OAI: oai:DiVA.org:su-30178DiVA, id: diva2:241952
Tillgänglig från: 2009-10-06 Skapad: 2009-10-06 Senast uppdaterad: 2017-12-13Bibliografiskt granskad
Ingår i avhandling
1. Activation and Regulation of TRPV1: Studies in Recombinant Human Neuroblastoma TRPV1-SHSY5Y Cells
Öppna denna publikation i ny flik eller fönster >>Activation and Regulation of TRPV1: Studies in Recombinant Human Neuroblastoma TRPV1-SHSY5Y Cells
2009 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

TRPV1 is a transmembrane non-selective cation channel with preference for Ca2+. The receptor is primarily localised on dorsal root ganglion neurons and is activated by numerous endogenous and exogenous potentially irritating ligands eliciting pain. The TRPV1 expression and activity are regulated by several neurotrophic agents and inflammatory mediators via activation of phosphorylation cascades.

In this thesis a stably TRPV1-expressing cell clone of the human neuroblastoma cell line SHSY5Y was established with the purpose to study regulation of TRPV1 through a straightforward and reproducible approach.

In paper I it is reported that the neurotrophic factors insulin, and IGF-1 up-regulate TRPV1 in the TRPV1-SHSY5Y cells. Additionally, the involved signalling pathways are suggested. This is of interest because both TRPV1 activity and expression is altered in diabetic patients with painful neuropathies, and so is insulin and IGF-1 signalling.

Results from paper II show that the neuronally differentiating morphogen retinoic acid (RA) increases TRPV1 protein levels and TRPV1-mediated Ca2+ influxes. Furthermore, the basal Ca2+ level is increased after RA treatment in TRPV1-SHSY5Y cells but not in native SHSY5Y cells. The TRPV1-SHSY5Y cells also develop into a more mature neuronal phenotype than the native SHSY5Y cells after six days of RA-induced differentiation. Hence, TRPV1 might be involved in neurogenesis.

In paper III-IV it is concluded that the TRPV1-SHSY5Y cells can be used in a semi-high throughput screening (HTS)-mode to adress TRPV1-mediated Ca2+ influxes. In this assay it is shown that anionic linear aliphatic surfactants might be potent ligands of TRPV1. As a concluding remark, the TRPV1–SHSY5Y cells can be utilised to assess activation and regulation of TRPV1 in an easy-to-use and robust model system.

Ort, förlag, år, upplaga, sidor
Stockholm: Department of Neurochemistry, Stockholm University, 2009. s. 91
Nyckelord
nociception, neurotrophic factors, eye irritation, stable transfection, Ca2+
Nationell ämneskategori
Neurovetenskaper
Forskningsämne
neurokemi med molekylär neurobiologi
Identifikatorer
urn:nbn:se:su:diva-30182 (URN)978-91-7155-954-8 (ISBN)
Disputation
2009-11-13, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 13:00 (Engelska)
Opponent
Handledare
Anmärkning
At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: In press. Paper 4: In press.Tillgänglig från: 2009-10-22 Skapad: 2009-10-06 Senast uppdaterad: 2018-01-13Bibliografiskt granskad

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