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Dolichol: A Component of the Cellular Antioxidant Machinery

  • Original Article
  • Published:
Lipids

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.

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Abbreviations

CoQ:

Coenzyme Q

DCFH-DA:

2′,7′-dichlorodihydro-fuorescein diacetate

FA:

Fatty acid(s)

FAME:

Fatty acid methyl esters

GC:

Gas–liquid chromatography

HMG-CoAR:

3-hydroxy-3-methylglutaryl CoA reductase

HPLC:

High-pressure liquid chromatography

MDA:

Malondialdehyde

OS:

Oxidative stress

PL:

Phospholipid(s)

PL-PUFA:

Phospholipid-bound polyunsaturated fatty acid(s)

ROS:

Reactive oxygen species

TBARS:

Thiobarbituric acid reactive substances

Trolox:

6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid

UV-B:

Ultraviolet-B

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Authors and Affiliations

  1. Interdepartmental Research Centre on Biology and Pathology of Aging, University of Pisa, Via Roma 55, 56126, Pisa, Italy

    Gabriella Cavallini, Ilaria Parentini, Alessio Donati & Ettore Bergamini

  2. Biophysics Institute of the National Research Council (IBF-CNR), Pisa, Italy

    Antonella Sgarbossa, Ranieri Bizzarri & Francesco Lenci

  3. NEST, Nanoscience Institute of the National Research Council (NANO-CNR) and Scuola Normale Superiore, Pisa, Italy

    Antonella Sgarbossa & Ranieri Bizzarri

Authors
  1. Gabriella Cavallini
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  2. Antonella Sgarbossa
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  3. Ilaria Parentini
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  4. Ranieri Bizzarri
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  5. Alessio Donati
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  6. Francesco Lenci
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  7. Ettore Bergamini
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Correspondence to Gabriella Cavallini.

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This paper is dedicated to the memory of Gabriele Chiti, a skilful technician and a dear friend of the Biophysics Institute of the National Research Council, who prematurely passed away.

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Cavallini, G., Sgarbossa, A., Parentini, I. et al. Dolichol: A Component of the Cellular Antioxidant Machinery. Lipids 51, 477–486 (2016). https://doi.org/10.1007/s11745-016-4137-x

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  • DOI: https://doi.org/10.1007/s11745-016-4137-x

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