Dolichol: A Component of the Cellular Antioxidant Machinery

Abstract

Dolichol, an end product of the mevalonate pathway, has been proposed as a biomarker of aging, but its biological role, not to mention its catabolism, has not been fully understood. UV-B radiation was used to induce oxidative stress in isolated rat hepatocytes by the collagenase method. Effects on dolichol, phospholipid-bound polyunsaturated fatty acids (PL-PUFA) and known lipid soluble antioxidants [coenzyme Q (CoQ) and α-tocopherol] were studied. The increase in oxidative stress was detected by a probe sensitive to reactive oxygen species (ROS). Peroxidation of lipids was assessed by measuring the release of thiobarbituric acid reactive substances (TBARS). Dolichol, CoQ, and α-tocopherol were assessed by high-pressure liquid chromatography (HPLC), PL-PUFA by gas-liquid chromatography (GC). UV-B radiation caused an immediate increase in ROS as well as lipid peroxidation and a simultaneous decrease in the levels of dolichol and lipid soluble antioxidants. Decrease in dolichol paralleled changes in CoQ levels and was smaller to that in α-tocopherol. The addition of mevinolin, a competitive inhibitor of the enzyme 3-hydroxy-3-methylglutaryl CoA reductase (HMG-CoAR), magnified the loss of dolichol and was associated with an increase in TBARS production. Changes in PL-PUFA were minor. These findings highlight that oxidative stress has very early and similar effects on dolichol and lipid soluble antioxidants. Lower levels of dolichol are associated with enhanced peroxidation of lipids, which suggest that dolichol may have a protective role in the antioxidant machinery of cell membranes and perhaps be a key to understanding some adverse effects of statin therapy.

Polyprenols Are Synthesized by a Plastidial cis-Prenyltransferase and Influence Photosynthetic Performance

“…However, it is noteworthy that AtCPT7 is highly upregulated in response to various environmental stresses (Zimmermann et al, 2004) and that polyprenols accumulate in such cases (Bajda et al, 2009;Jozwiak et al, 2013;Milewska-Hendel et al, 2017). Given that plastid membranes experience changes in dynamics in response to stress, it is tempting to speculate that the stressinduced accumulation of polyprenols may serve a protective role for plastids in these environments, either as a ballast to support the integrity of thylakoids and/or envelope membranes or as an antioxidant, as recently postulated (Cavallini et al, 2016).…”

Plant polyprenols reduce demyelination and recover impaired oligodendrogenesis and neurogenesis in the cuprizone murine model of multiple sclerosis

“…Polyprenols can accumulate at relatively high levels within eukaryotic organisms (Hartley & Imperiali, 2012). Unsaturated plant polyprenols and dolichols are known as potent antioxidants (Cavallini et al, 2016;Swiezewska & Danikiewicz, 2005). Either directly or after conversion to dolichols in eukaryotic cells via polyprenol reductase pathway (Swiezewska & Danikiewicz, 2005), polyprenols may work as scavengers for reactive oxygen and nitrogen species, thus protecting cells from the oxidative stress.…”

Metabolomics profiling reveals new aspects of dolichol biosynthesis in Plasmodium falciparum

“…Recently, cis -polyisoprenoids gained special attention due to several breakthroughs in the field including improvements in the analytical techniques for their analysis 17 , 18 , partial identification of their enzymatic machinery 19 , and the discovery of new biological functions beyond glycosylation 20 , 21 . Among some of these biological functions are the regulation of the membrane fluidity 21 , 22 , stimulation of spore wall formation in yeast 20 , and scavenging free radicals in cell membranes 23 – 25 . Interestingly, in cancer cells 26 and P. falciparum 27 , protein dolichylation occurs as a post-translational event, but functions of such derivatives and enzymes involved in this posttranslational protein lipid modification remain unknown.…”