title: 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.
authors.affiliation: Interdepartmental Research Centre on Biology and Pathology of Aging, University of Pisa, Via Roma 55, 56126, Pisa, Italy. gabriella.cavallini@med.unipi.it.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Cavallini
authors.affiliation: Biophysics Institute of the National Research Council (IBF-CNR), Pisa, Italy.|NEST, Nanoscience Institute of the National Research Council (NANO-CNR) and Scuola Normale Superiore, Pisa, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Sgarbossa
authors.affiliation: Interdepartmental Research Centre on Biology and Pathology of Aging, University of Pisa, Via Roma 55, 56126, Pisa, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Parentini
authors.affiliation: Biophysics Institute of the National Research Council (IBF-CNR), Pisa, Italy.|NEST, Nanoscience Institute of the National Research Council (NANO-CNR) and Scuola Normale Superiore, Pisa, Italy.
authors.forename: Ranieri
authors.initials: R
authors.lastname: Bizzarri
authors.affiliation: Interdepartmental Research Centre on Biology and Pathology of Aging, University of Pisa, Via Roma 55, 56126, Pisa, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Donati
authors.affiliation: Biophysics Institute of the National Research Council (IBF-CNR), Pisa, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Lenci
authors.affiliation: Interdepartmental Research Centre on Biology and Pathology of Aging, University of Pisa, Via Roma 55, 56126, Pisa, Italy.
authors.forename: Ettore
authors.initials: E
authors.lastname: Bergamini
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000032:analysis*; D002478:Cells, Cultured; D002853:Chromatography, Liquid / Q000379:methods; D004286:Dolichols / Q000032:analysis*; D022781:Hepatocytes / Q000166:cytology / Q000528:radiation effects*; D015227:Lipid Peroxidation / Q000528:radiation effects; D008297:Male; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D000975:Antioxidants; D004286:Dolichols; D017382:Reactive Oxygen Species
keywords: Coenzyme Q; Dolichol; Oxidative stress; Phospholipid-bound polyunsaturated fatty acids; Rat hepatocytes; α-Tocopherol