题名

The Carcinogen Safrole Increases Intracellular Free Ca(superscript 2+) Levels and Causes Death in MDCK Cells

作者

Wei-Chuan Chen;He-Hsiung Cheng;Chun-Jen Huang;Yih-Chau Lu;I-Shu Chen;Shiuh-Inn Liu;Shu-Shong Hsu;Hong-Tai Chang;Jong-Khing Huang;Jin-Shyr Chen;Chung-Ren Jan

关键词

Ca(superscript 2+) ; Ca(superscript 2+) stores ; fura-2 ; MDCK ; renal tubular cells ; safrole

期刊名称

The Chinese Journal of Physiology

卷期/出版年月

50卷1期(2007 / 02 / 28)

页次

34 - 40

内容语文

英文

英文摘要

The effect of the carcinogen safrole on intracellular Ca(superscript 2+) movement in renal tubular cells has not been explored previously. The present study examined whether safrole could alter Ca(superscript 2+) handling in Madin-Darby canine kidney (MDCK) cells. Cytosolic free Ca(superscript 2+) levels ([Ca(superscript 2+)](subscript i)) in populations of cells were measured using fura-2 as a fluorescent Ca(superscript 2+) probe. Safrole at concentrations above 33 μM increased [Ca(superscript 2+)](subscript i) in a concentration-dependent manner with an EC50 value of 400 μM. The Ca(superscript 2+) signal was reduced by 90% by removing extracellular Ca(superscript 2+), but was not affected by nifedipine, verapamil, or diltiazem. Addition of Ca(superscript 2+) after safrole had depleted intracellular Ca(superscript 2+)-induced dramatic Ca(superscript 2+) influx, suggesting that safrole caused store-operated Ca(superscript 2+) entry. In Ca(superscript 2+)-free medium, after pretreatment with 650 μM safrole, 1 μM thapsigargin (an endoplasmic reticulum Ca(superscript 2+) pump inhibitor) failed to release more Ca(superscript 2+). Inhibition of phospholipase C with 2 μM U73122 did not affect safrole-induced Ca(superscript 2+) release. Trypan blue exclusion assays revealed that incubation with 650 μM safrole for 30 min did not kill cells, but killed 70% of cells after incubation for 60 min. Collectively, the data suggest that in MDCK cells, safrole induced a [Ca(superscript 2+)](subscript i) increase by causing Ca(superscript 2+) release from the endoplasmic reticulum in a phospholipase C-independent fashion, and by inducing Ca(superscript 2+) influx via store-operated Ca(superscript 2+) entry. Furthermore, safrole can cause acute toxicity to MDCK cells.

主题分类 醫藥衛生 > 基礎醫學
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被引用次数
  1. Shieh, Pochuen,Liang, Wei-Zhe,Kuo, Daih-Huang,Kuo, Chun-Chi,Jan, Chung-Ren,Ho, Chin-Man,Chou, Chiang-Ting,Chien, Jau-Min(2014).The Mechanism of NPC-14686-Induced [Ca2+]i Rises and Non-Ca2+-Triggered Cell Death in MG63 Human Osteosarcoma Cells.中國生理學雜誌,57(3),158-166.
  2. Shieh, Pochuen,Lu, Ti,Liang, Wei-Zhe,Kuo, Daih-Huang,Jan, Chung-Ren,Ho, Chin-Man,Chou, Chiang-Ting,Chang, Hong-Tai(2014).Effects of Thymol on Ca2+ Homeostasis and Apoptosis in MDCK Renal Tubular Cells.中國生理學雜誌,57(2),90-98.
  3. Sun, Te-Kung,Shieh, Pochuen,Lin, Jia-Rong,Liang, Wei-Zhe,Li, Yih-Do,Kuo, Daih-Huang,Kuo, Chun-Chi,Jan, Chung-Ren,Hung, Tzu-Yi,Ho, Chin-Man,Fang, Yi-Chien,Chou, Chiang-Ting,Cheng, Jin-Shiung(2015).The Mechanism of Safrole-Induced [Ca2+]i Rises and Non-Ca2+-Triggered Cell Death in SCM1 Human Gastric Cancer Cells.中國生理學雜誌,58(5),302-311.
  4. Tsai, Jeng-Yu,Lu, Yi-Chau,Lu, Ti,Liu, Shiuh-Inn,Liou, Wen-Chin,Lin, Ko-Long,Liao, Wei-Chuan,Liang, Wei-Zhe,Jan, Chung-Ren,Hsu, Shu-Shong,Chou, Chiang-Ting,Chen, Wei-Chuan(2014).Rise of [Ca2+]i and Apoptosis Induced by M-3M3FBS in SCM1 Human Gastric Cancer Cells.中國生理學雜誌,57(1),31-40.
  5. Wang, Jue-Long,Shieh, Pochuen,Liang, Wei-Zhe,Kuo, Chun-Chi,Jan, Chung-Ren,Chou, Chiang-Ting,Cheng, He-Hsiung(2017).Effect of Protriptyline on [Ca2+]i and Viability in MDCK Renal Tubular Cells.中國生理學雜誌,60(2),114-123.