A study of the cytotoxicity of branched-chain phytanic acid with mitochondria and rat brain astrocytes

Experimental Gerontology
Peter SchönfeldGeorg Reiser

Abstract

Phytanic acid, a saturated fatty acid of 20-carbon-atoms with isoprenoic structure, is formed from the phytol-side chain of chlorophyll in ruminants. Degradation of phytanic acid is blocked in Refsum disease by several enzymatic defects of peroxisomal degradation of branched-chain fatty acids. Refsum disease is an inherited neurological disorder progressively developing from early childhood to adultness. Clinical signs are attributed to toxicity of phytanic acid, which accumulates to unusually high levels in the tissue and serum of patients suffering from untreated Refsum disease. We report here that hippocampal astrocytes isolated from rat brain, which were exposed to phytanic acid (50 microM) die within a few hours. In situ depolarization of mitochondria and an increase of cytosolic Ca2+ precede cell death. Therefore, we also investigated the influence of phytanic acid on physiology of mitochondria isolated from rat brain. Mitochondria become functionally impaired by phytanic acid, as indicated by uncoupling (resting state), inhibition of the electron transport (state 3), stimulation of ROS-generation, decline of Ca2+ loading and severe release of cytochrome c. Thus, phytanic acid seems to initiate astrocyte cell death by act...Continue Reading

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Citations

Nov 14, 2008·Proceedings of the National Academy of Sciences of the United States of America·Sacha FerdinandussePedro Brites
Jun 19, 2010·Journal of Lipid Research·Paul P Van Veldhoven
Feb 5, 2013·Progress in Lipid Research·Matthew D LloydTimothy J Woodman
Jun 16, 2015·Frontiers in Cell and Developmental Biology·Celien LismontMarc Fransen
Aug 23, 2019·European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (ECP)·Gerd BobeYumie Takata

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