BDE-47 and 6-OH-BDE-47 modulate calcium homeostasis in primary fetal human neural progenitor cells via ryanodine receptor-independent mechanisms

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Fältnamn	Indikatorer	Metadata
000		04156naa a2200553 4500
001		oai:DiVA.org:su-107017
003		SwePub
008		140902s2014 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
009		oai:prod.swepub.kib.ki.se:129486527
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-1070172 URI
024	7	a https://doi.org/10.1007/s00204-014-1217-72 DOI
024	7	a http://kipublications.ki.se/Default.aspx?queryparsed=id:1294865272 URI
040		a (SwePub)sud (SwePub)ki
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Gassmann, Kathrin4 aut
245	1 0	a BDE-47 and 6-OH-BDE-47 modulate calcium homeostasis in primary fetal human neural progenitor cells via ryanodine receptor-independent mechanisms
264		c 2014-03-06
264	1	b Springer Science and Business Media LLC,c 2014
338		a print2 rdacarrier
500		a AuthorCount:13;
520		a Polybrominated diphenyl ethers (PBDEs) are bioaccumulating flame retardants found in rising concentrations in human tissue. Epidemiological and animal studies have raised concern for their potential to induce developmental neurotoxicity (DNT). Considering the essential role of calcium homeostasis in neurodevelopment, PBDE-induced disturbance of intracellular calcium concentration ([Ca2+](i)) may underlie PBDE-induced DNT. To test this hypothesis, we investigated acute effects of BDE-47 and 6-OH-BDE-47 on [Ca2+](i) in human neural progenitor cells (hNPCs) and unraveled involved signaling pathways. Short-time differentiated hNPCs were exposed to BDE-47, 6-OH-BDE-47, and multiple inhibitors/stimulators of presumably involved signaling pathways to determine possible effects on [Ca2+](i) by single-cell microscopy with the fluorescent dye Fura-2. Initial characterization of calcium signaling pathways confirmed the early developmental stage of hNPCs. In these cells, BDE-47 (2 mu M) and 6-OH-BDE-47 (0.2 mu M) induce [Ca2+](i) transients. This increase in [Ca2+](i) is due to extracellular Ca2+ influx and intracellular release of Ca2+, mainly from the endoplasmic reticulum (ER). While extracellular Ca2+ seems to enter the cytoplasm upon 6-OH-BDE-47 by interfering with the cell membrane and independent of Ca2+ ion channels, ER-derived Ca2+ is released following activation of protein lipase C and inositol 1,4,5-trisphosphate receptor, but independently of ryanodine receptors. These findings illustrate that immature developing hNPCs respond to low concentrations of 6-OH-BDE-47 by an increase in [Ca2+](i) and provide new mechanistic explanations for such BDE-induced calcium disruption. Thus, these data support the possibility of a critical window of PBDE exposure, i.e., early human brain development, which has to be acknowledged in risk assessment.
650	7	a NATURVETENSKAPx Kemi0 (SwePub)1042 hsv//swe
650	7	a NATURAL SCIENCESx Chemical Sciences0 (SwePub)1042 hsv//eng
653		a Brominated flame retardant
653		a Calcium
653		a Human neural progenitor cell
653		a Neurotoxicity
653		a Polybrominated diphenyl ether
653		a Ryanodine receptor
700	1	a Schreiber, Timm4 aut
700	1	a Dingemans, Milou M. L.4 aut
700	1	a Krause, Guido4 aut
700	1	a Roderigo, Claudia4 aut
700	1	a Giersiefer, Susanne4 aut
700	1	a Schuwald, Janette4 aut
700	1	a Moors, Michaela4 aut
700	1	a Unfried, Klaus4 aut
700	1	a Bergman, Åkeu Karolinska Institutet,Stockholms universitet,Avdelningen för miljökemi4 aut0 (Swepub:su)alb
700	1	a Westerink, Remco H. S.4 aut
700	1	a Rose, Christine R.4 aut
700	1	a Fritsche, Ellen4 aut
710	2	a Stockholms universitetb Avdelningen för miljökemi4 org
773	0	t Archives of Toxicologyd : Springer Science and Business Media LLCg 88:8, s. 1537-1548q 88:8<1537-1548x 0340-5761x 1432-0738
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-107017
856	4 8	u https://doi.org/10.1007/s00204-014-1217-7
856	4 8	u http://kipublications.ki.se/Default.aspx?queryparsed=id:129486527

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Av författaren/redakt...: Gassmann, Kathri ...; Schreiber, Timm; Dingemans, Milou ...; Krause, Guido; Roderigo, Claudi ...; Giersiefer, Susa ...; visa fler...; Schuwald, Janett ...; Moors, Michaela; Unfried, Klaus; Bergman, Åke; Westerink, Remco ...; Rose, Christine ...; Fritsche, Ellen; visa färre...

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