Polychlorinated biphenyl 19 blocks the most common form of store-operated Ca2+ entry through Orai
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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.
KeywordsPolychlorinated 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.).
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Competing financial interests
The authors declare that they have no competing financial interests.
- Dragoni S, Laforenza U, Bonetti E, Reforgiato M, Poletto V, Lodola F, Bottino C, Guido D, Rappa A, Pareek S, Tomasello M, Guarrera MR, Cinelli MP, Aronica A, Guerra G, Barosi G, Tanzi F, Rosti V, Moccia F (2014) Enhanced expression of Stim, Orai, and TRPC transcripts and proteins in endothelial progenitor cells isolated from patients with primary myelofibrosis. PLoS One 9:e91099CrossRefPubMedPubMedCentralGoogle Scholar
- EFSA (European Food Safety Authority) (2005) Opinion of the scientific panel on contaminants in the food chain on a request from the commission related to the presence of non dioxin-like polychlorinated biphenyls (PCB) in feed and food. EFSA J 284:1–137Google Scholar
- Harrad S, Goosey E, Desborough J, Abdallah MA, Roosens L, Covaci A (2010) Dust from U.K. primary school classrooms and daycare centers: the significance of dust as a pathway of exposure of young U.K. children to brominated flame retardants and polychlorinated biphenyls. Environ Sci Technol 44:4198–4202CrossRefPubMedGoogle Scholar
- Landman N, Jeong SY, Shin SY, Voronov SV, Serban G, Kang MS, Park MK, Di Paolo G, Chung S, Kim TW (2006) Presenilin mutations linked to familial Alzheimer’s disease cause an imbalance in phosphatidylinositol 4,5-bisphosphate metabolism. Proc Natl Acad Sci U S A 103:19524–19529CrossRefPubMedPubMedCentralGoogle Scholar
- Van den Berg M, Birnbaum LS, Denison M, De Vito M, Farland W, Feeley M, Fiedler H, Hakansson H, Hanberg A, Haws L, Rose M, Safe S, Schrenk D, Tohyama C, Tritscher A, Tuomisto J, Tysklind M, Walker N, Peterson RE (2006) The 2005 World Health Organization reevaluation of human and mammalian toxic equivalency factors for dioxins and dioxin-like compounds. Toxicol Sci 93:223–241CrossRefPubMedPubMedCentralGoogle Scholar