Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 390, Issue 12, pp 1221–1228 | Cite as

Polychlorinated biphenyl 19 blocks the most common form of store-operated Ca2+ entry through Orai

  • Keimin Lee
  • Yoon-Jung Kim
  • Yoon Young Cho
  • Sungkwon Chung
  • Su-Hyun JoEmail author
  • Se-Young ChoiEmail author
Original Article


PCB19, a 2,2′,6-trichlorinated biphenyl, is one of many non-dioxin-like polychlorinated biphenyls (NDL-PCBs), which are ubiquitous pollutants. NDL-PCBs affect cytosolic Ca2+ signaling by promoting Ca2+ release from ryanodine receptor-sensitive Ca2+ pools and inhibiting store-operated Ca2+ entry (SOCE) from the extracellular space. However, NDL-PCB-mediated SOCE inhibition has only been demonstrated in PC12 cells, in which SOCE is thought to be mainly mediated by TRPC family channels. Here, we investigated the effect of PCB19 on SOCE using human embryonic kidney 293 (HEK293) cells, human leukemia T cell line Jurkat-T cells and human promyelocytoma HL-60 cells which are the cell lines that are previously demonstrated to mediate the most common form of SOCE solely by the intrinsic Orai channels. PCB19 reduced thapsigargin-induced Ca2+ influx after Ca2+ pool depletion in HEK293 cells. SOCEs in HEK293, Jurkat T, HL-60 and PC12 cells showed distinct sensitivities to SOCE inhibitors such as Gd3+ and ML-9; however, PCB19 also showed a common effect of inhibiting SOCEs in all cell lines. PCB19-mediated SOCE inhibition was confirmed by demonstrating the ability of PCB19 to inhibit the SOCE current but not the TRPM7 current. These results imply that PCB19 inhibits not only TRPC-mediated SOCE as in PC12 cells but also Orai-mediated SOCE as in many other cells including HEK293, Jurkat T and HL-60 cells.


Polychlorinated biphenyl PCB19 NDL-PCB Ca2+ signaling Orai Store-operated Ca2+ entry 



We are grateful to Mr. Han-Hee Lee for reading the manuscript. This work was supported by the National Research Foundation of Korea (2016M3C7A1905481, 2016R1A2B4006811 to S.Y.C.) and Kangwon National University (520150351 to S.H.J.).

Compliance with ethical standards

Competing financial interests

The authors declare that they have no competing financial interests.

Supplementary material

210_2017_1420_Fig7_ESM.gif (263 kb)
Figure S1

Cytotoxicity of PCB19. (a) Cell images of PC12, HEK293, Jurkat T and HL-60 cells are obtained at 0 min (top), 20 min (middle) and 24 h (bottom) after the incubation with 30 μM PCB19. Scale bar, 20 μm for Jurkat T and HL-60 cells; 100 μm for PC12 and HEK293 cells. (b) Cells were incubated with 30 μM PCB19 for 20 min (dark gray bar) or 24 h (light gray bar), then harvested and analyzed with WST-1 cytotoxicity assay kit. Cell viability was depicted with % of vehicle-treated controls (black bar). Each bar represents mean ± SEM. *P < 0.05. (GIF 263 kb)

210_2017_1420_MOESM1_ESM.eps (5.7 mb)
High-Resolution Image (EPS 5860 kb)


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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Department of Physiology, Dental Research InstituteSeoul National University School of DentistrySeoulSouth Korea
  2. 2.Department of PhysiologySungkyunkwan University School of MedicineSuwonSouth Korea
  3. 3.Department of PhysiologyKangwon National University School of MedicineChuncheonSouth Korea

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