Calcium-Related Processes Involved in the Inhibition of Depolarization-Evoked Calcium Increase by Hydroxylated PBDEs in PC12 Cells
2010 (English)In: Toxicological Sciences, ISSN 1096-6080, E-ISSN 1096-0929, Vol. 114, no 2, 302-309 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2010. Vol. 114, no 2, 302-309 p.
brominated flame retardant, calcium homeostasis, calcium signaling, calcium-induced VGCC inhibition, depolarization-evoked calcium influx, in vitro neurotoxicity
IdentifiersURN: urn:nbn:se:su:diva-50684DOI: 10.1093/toxsci/kfp310ISI: 000276350200014OAI: oai:DiVA.org:su-50684DiVA: diva2:382295
authorCount :42010-12-302010-12-302010-12-30Bibliographically approved