Journal
TOXICOLOGY AND APPLIED PHARMACOLOGY
Volume 251, Issue 2, Pages 163-168Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2011.01.002
Keywords
Perfluorinated acid; Calcium homeostasis; Mitochondria; Apoptosis; Cell signaling; HCT116 cells
Categories
Funding
- Polish Ministry of Research and Higher Education [2 P04G 118 29, DS 8390-4-0141-6]
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The global distribution of perfluorinated acids (PFAs) in industry and in household is well known. Their increasing environmental occurrence and biomagnification in the living organisms have drawn growing interests in efforts to describe precisely the mechanisms of action in vitro and in vivo. Our previous investigations widely described lipophilicity-dependent cytotoxicity of PFAs as well as the effect of perfluorination of carbon chain on depolarization of plasma membrane potential, acidification or mitochondrial dysfunctions. In this study we presented in dose- and time-dependent manner the impact of PFAs on calcium homeostasis in HCT116 cells. Comparative analysis of cytosolic [Ca2+](c) and mitochondrial calcium [Ca2+](m) carried out by flow cytometry revealed distinct uptake of calcium into mitochondria in correlation to increasing lipophilicity of PFAs. Massive accumulation of [Ca2+](m) was not accompanied by equivalent loss of [Ca2+](c). Indeed, moderate changes of [Ca2+](c) were observed after incubation with 400 mu m PFDoDA reaching 29.83% and 49.17% decrease at 4th and 72nd hour, respectively. At the same time, mitochondrial calcium uptake increased from 2- to more than 4-fold comparing with non-treated cells. Incubation with non-fluorinated decanoic acid (DA) did not cause any changes in calcium homeostasis. Presented data show that PFAs-induced perturbations in calcium distribution seem to be a missing link related to mitochondria dysfunction playing a crucial role in determination of apoptotic cell death. Complete scheme for the mechanism of cytotoxic action of PFAs has been included. (C) 2011 Elsevier Inc. All rights reserved.
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