Peroxisomes attenuate cytotoxicity of very long-chain fatty acids.
Biochim Biophys Acta Mol Cell Biol Lipids
; 1868(2): 159259, 2023 02.
Article
em En
| MEDLINE
| ID: mdl-36460260
ABSTRACT
One of the major functions of peroxisomes in mammals is oxidation of very long-chain fatty acids (VLCFAs). Genetic defects in peroxisomal ß-oxidation result in the accumulation of VLCFAs and lead to a variety of health problems, such as demyelination of nervous tissues. However, the mechanisms by which VLCFAs cause tissue degeneration have not been fully elucidated. Recently, we found that the addition of small amounts of isopropanol can enhance the solubility of saturated VLCFAs in an aqueous medium. In this study, we characterized the biological effect of extracellular VLCFAs in peroxisome-deficient Chinese hamster ovary (CHO) cells, neural crest-derived pheochromocytoma cells (PC12), and immortalized adult Fischer rat Schwann cells (IFRS1) using this solubilizing technique. C200 FA was the most toxic of the C16-C26 FAs tested in all cells. The basis of the toxicity of C200 FA was apoptosis and was observed at 5 µM and 30 µM in peroxisome-deficient and wild-type CHO cells, respectively. The sensitivity of wild-type CHO cells to cytotoxic C200 FA was enhanced in the presence of a peroxisomal ß-oxidation inhibitor. Further, a positive correlation was evident between cell toxicity and the extent of intracellular accumulation of toxic FA. These results suggest that peroxisomes are pivotal in the detoxification of apoptotic VLCFAs by preventing their accumulation.
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Base de dados:
MEDLINE
Assunto principal:
Peroxissomos
/
Ácidos Graxos
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article