Peroxisomes attenuate cytotoxicity of very long-chain fatty acids

One of the major functions of peroxisomes in mammals is oxidation of very long-chain fatty acids (VLCFAs). Genetic defects in peroxisomal 8-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. C20:0 FA was the most toxic of the C16-C26 FAs tested in all cells. The basis of the toxicity of C20:0 FA was apoptosis and was observed at 5 mu M and 30 mu M in peroxisome-deficient and wild-type CHO cells, respectively. The sensitivity of wild-type CHO cells to cytotoxic C20:0 FA was enhanced in the presence of a peroxisomal 8-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.

Automated summary

One of the major functions of peroxisomes in mammals is to oxidize very long-chain fatty acids (VLCFAs), which if accumulated due to genetic defects in peroxisomal β-oxidation, can lead to various health problems. The biological effect of extracellular VLCFAs was characterized using a solubilizing technique in peroxisome-deficient CHO cells, PC12 cells, and IFRS1 cells. The study found that C20:0 fatty acid was the most toxic among the tested C16-C26 FAs, causing apoptosis in cells. Peroxisomes play a crucial role in detoxifying apoptotic VLCFAs by preventing their accumulation.