Oxidation by thimerosal increases calcium levelsin renal tubular cells.
The effect of thimerosal, a reactive oxidant, on cytoplasmic free Ca2+ concentrations ([Ca2+]i) in Madin Darby canine kidney (MDCK) cells was explored by using the Ca2+-sensitive dye fura-2. Thimerosal acted in a concentration-dependent manner with an EC50 of 0.5 microM. The Ca2+ signal comprised a gradual rise and a sustained elevation. Removal of extracellular Ca2+ reduced 80% of the signal. In Ca2+-free medium, the [Ca2+]i rise induced by 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor) was completely inhibited by pretreatment with 5 microM thimerosal. The thimerosal (5 microM)-induced Ca2+ release was not changed by inhibition of phospholipase C with 2 microM U73122. Collectively, this study shows that thimerosal induced [Ca2+]i rises in renal tubular cells via releasing store Ca2+ from the endoplasmic reticulum Ca2+ stores in a manner independent of phospholipase C activity.
Jan
Chung-Ren
CR
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 813.
Jiann
Bang-Ping
BP
Lu
Yih-Chau
YC
Chang
Hong-Tai
HT
Yu
Chia-Cheng
CC
Chen
Wei-Chung
WC
Huang
Jong-Khing
JK
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004285:Dogs; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D045604:Extracellular Fluid / Q000378:metabolism; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016877:Oxidants / Q000633:toxicity*; D010084:Oxidation-Reduction; D013439:Sulfhydryl Reagents / Q000633:toxicity*; D013849:Thimerosal / Q000633:toxicity*; D013997:Time Factors; D010738:Type C Phospholipases / Q000378:metabolism
D016877:Oxidants; D013439:Sulfhydryl Reagents; D013849:Thimerosal; D010738:Type C Phospholipases; D002118:Calcium