Orai1-STIM1 formed store-operated Ca2+ channels (SOCs) as the molecular components needed for Pb2+ entry in living cells

Toxicology and Applied Pharmacology
Yu-Fen ChangDe-Ming Yang

Abstract

Heavy metal lead (Pb2+) is a pollutant and causes severe toxicity when present in human tissues especially the nervous system. Recent reviews have suggested that Pb2+ can target Ca2+-related proteins within neurons and that Ca2+ channels might be a candidate for Pb2+ entry. This study's main aim was to identify the functional entry pathway of Pb2+ into living cells. We firstly characterized the endogenous expression of Orai1 and STIM1 mRNA together with the level of thapsigargin (TG) stimulated capacitative Ca2+ entry in PC12 and HeLa cells; this was done by RT-PCR and time-lapse Ca2+ imaging microscopy, respectively. Our data supported Orai1 and STIM1 as contributing to store-operated Ca2+ channel (SOC) basal activity. Secondly, using the indo-1 quenching method with the SOC blocker 2-APB, we observed that Pb2+ was able to enter cells directly through unactivated SOCs without TG pretreatment. Thirdly, we further demonstrated that co-expression of Orai1 and STIM1 differentially enhanced SOC functional activity (4-fold with PC12 and 5-fold with HeLa cells) and Pb2+ entry (5- to 7-fold with PC12 and 2-fold with HeLa cells). Furthermore, after a 1 h of Pb2+ exposure, the depolarization- and histamine-induced Ca2+ responses were si...Continue Reading

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Citations

May 12, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Tai-Yu ChiuDe-Ming Yang
Jan 14, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Tai-Yu Chiu, De-Ming Yang
Jul 14, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Henk P M Vijverberg, Remco H S Westerink
Apr 10, 2010·Microscopy and Microanalysis : the Official Journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada·Ping-Chun HuangDe-Ming Yang
Jun 16, 2010·Pharmacology & Therapeutics·Sarah J Roberts-ThomsonGregory R Monteith
Feb 27, 2020·Journal of the Chinese Medical Association : JCMA·De-Ming YangYu-Fen Chang
May 19, 2009·The Journal of Pharmacology and Experimental Therapeutics·De-Ming YangChen-Hsen Lee
Jul 6, 2021·Journal of the Chinese Medical Association : JCMA·Tai-Jay ChangDe-Ming Yang

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