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Altered mRNA Expres...
Altered mRNA Expression and Cell Membrane Potential in the Differentiated C17.2 Cell Model as Indicators of Acute Neurotoxicity
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- Lundqvist, Jessica (författare)
- Stockholms universitet,Institutionen för neurokemi
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- Christina, Svensson (författare)
- Stockholms universitet,Institutionen för neurokemi
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- Kristina, Attoff (författare)
- Stockholms universitet,Institutionen för neurokemi
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- Forsby, Anna (författare)
- Stockholms universitet,Institutionen för neurokemi,Swetox, Karolinska Institutet, Sweden
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(creator_code:org_t)
- Mary Ann Liebert Inc, 2017
- 2017
- Engelska.
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Ingår i: Applied In Vitro Toxicology. - : Mary Ann Liebert Inc. - 2332-1539 .- 2332-1512. ; 3:2, s. 154-162
- Relaterad länk:
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https://doi.org/10.1...
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https://www.liebertp...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Using general cytotoxicity assays in combination with in vitro tests for organ-specific toxicity has been proposed as an alternative approach to animal tests for estimation of acute systemic toxicity. Here, we present the C17.2 neural progenitor cell line as an option for estimation of acute neurotoxicity. The C17.2 cells were differentiated for 6 days in serum-free N2 medium with brain-derived neurotrophic factor and nerve growth factor to a mixed culture of neurons and astrocytes. The cells were then exposed to noncytotoxic concentrations of acetylsalicylic acid, atropine, digoxin, ethanol, nicotine, or strychnine for 48 hours and the mRNA levels of glial fibrillary acidic protein, βIII-tubulin, and heat shock protein 32 were analyzed as biomarkers for astrocytes, neurons, and cellular stress respectively. As a functional endpoint, the cell membrane potential (CMP) was monitored after acute addition of each compound to the differentiated C17.2 cells, by using the fluorescent FLIPR® membrane potential assay. Nicotine [3.2E-04 M], atropine [1.2E-05 M], or strychnine [6.4E-05 M] resulted in altered gene expression of at least one biomarker for each compound, indicating alerts for neurotoxicity. The three compounds also induced depolarization of the CMP at the lowest observed effect concentrations 9.5E-05 M of nicotine, 1.5E-05 M of atropine, and 6.9E-07 M of strychnine. The non-neurotoxic compounds acetylsalicylic acid, ethanol, and digoxin did neither affect the mRNA levels, nor the CMP. This study showed that the differentiated C17.2 cells might be useful for estimation of acute neurotoxicity by analyzing expression of mRNA biomarkers and CMP alterations.
Ämnesord
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- NATURVETENSKAP -- Kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences (hsv//eng)
Nyckelord
- acute neurotoxicity
- astrocytes
- C17.2 cells
- cell membrane potential
- HSP32
- mRNA biomarkers
- neuronal in vitro model
- neurons
- neurokemi med molekylär neurobiologi
- Neurochemistry with Molecular Neurobiology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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