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Calcium-Related Pro...
Calcium-Related Processes Involved in the Inhibition of Depolarization-Evoked Calcium Increase by Hydroxylated PBDEs in PC12 Cells
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Dingemans, Milou M. L. (author)
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van den Berg, Martin (author)
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- Bergman, Åke (author)
- Stockholms universitet,Institutionen för material- och miljökemi (MMK)
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Westerink, Remco H. S. (author)
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(creator_code:org_t)
- 2009-12-31
- 2010
- English.
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In: Toxicological Sciences. - : Oxford University Press (OUP). - 1096-6080 .- 1096-0929. ; 114:2, s. 302-309
- Related links:
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https://academic.oup...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- In vitro studies indicated that hydroxylated polybrominated diphenyl ethers (OH-PBDEs) have an increased toxic potential compared to their parent congeners. An example is the OH-PBDE–induced increase of basal intracellular Ca2+ concentration ([Ca2+]i) by release of Ca2+ from endoplasmic reticulum (ER) and mitochondria and/or influx of extracellular Ca2+. ER and mitochondria regulate Ca2+ homeostasis in close association with voltage-gated Ca2+ channels (VGCCs). Therefore, effects of (OH-)PBDEs on the depolarization-evoked (100mM K+) net increase in [Ca2+]i (depolarization-evoked [Ca2+]i) were measured in neuroendocrine pheochromocytoma cells using the Ca2+-responsive dye Fura-2. OH-PBDEs dose dependently inhibited depolarization-evoked [Ca2+]i. This inhibition was potentiated by a preceding increase in basal [Ca2+]i. Especially at higher concentrations of OH-PBDEs (5–20μM), large increases in basal [Ca2+]i strongly inhibited depolarization-evoked [Ca2+]i. The inhibition appeared more sensitive to increases in basal [Ca2+]i by Ca2+ release from intracellular stores (by 3-OH-BDE-47 or 6′-OH-BDE-49) compared to those by influx of extracellular Ca2+ (by 6-OH-BDE-47 or 5-OH-BDE-47). The expected [Ca2+]i difference close to the membrane suggests involvement of Ca2+-dependent regulatory processes close to VGCCs. When coapplied with depolarization, some OH-PBDEs induced also moderate direct inhibition of depolarization-evoked [Ca2+]i. Polybrominated diphenyl ethers and methoxylated BDE-47 affected neither basal nor depolarization-evoked [Ca2+]i, except for BDE-47, which moderately increased fluctuations in basal [Ca2+]i and depolarization-evoked [Ca2+]i. These findings demonstrate that OH-PBDEs inhibit depolarization-evoked [Ca2+]i depending on preceding basal [Ca2+]i. Related environmental pollutants that affect Ca2+ homeostasis (e.g., polychlorinated biphenyls) may thus also inhibit depolarization-evoked [Ca2+]i, justifying further investigation of possible mixture effects of environmental pollutants on Ca2+ homeostasis.
Subject headings
- NATURVETENSKAP -- Geovetenskap och miljövetenskap -- Miljövetenskap (hsv//swe)
- NATURAL SCIENCES -- Earth and Related Environmental Sciences -- Environmental Sciences (hsv//eng)
Keyword
- brominated flame retardant
- calcium homeostasis
- calcium signaling
- calcium-induced VGCC inhibition
- depolarization-evoked calcium influx
- in vitro neurotoxicity
- Environmental chemistry
- Miljökemi
Publication and Content Type
- ref (subject category)
- art (subject category)
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