Mechanism of cytotoxic action of perfluorinated acids. III. Disturbance in Ca{sup 2+} homeostasis

Journal Article · Mon Feb 28 23:00:00 EST 2011 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2011.01.002· OSTI ID:21535245

Kleszczynski, Konrad

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 [Ca{sup 2+}]{sub c} and mitochondrial calcium [Ca{sup 2+}]{sub m} carried out by flow cytometry revealed distinct uptake of calcium into mitochondria in correlation to increasing lipophilicity of PFAs. Massive accumulation of [Ca{sup 2+}]{sub m} was not accompanied by equivalent loss of [Ca{sup 2+}]{sub c}. Indeed, moderate changes of [Ca{sup 2+}]{sub 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.

• OSTI ID: 21535245
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 2 Vol. 251; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ACIDIFICATION
ALKALINE EARTH METALS
APOPTOSIS
CALCIUM
CALCIUM IONS
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CHARGED PARTICLES
DECANOIC ACID
DISTRIBUTION
DISTURBANCES
ELEMENTS
HOMEOSTASIS
IN VITRO
IN VIVO
IONS
METALS
MITOCHONDRIA
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
TIME DEPENDENCE
TOXICITY
UPTAKE