Universität zu Köln

Hagmann, Henning, Kuczkowski, Alexander, Ruehl, Michael, Lamkemeyer, Tobias, Brodesser, Susanne, Horke, Sven, Dryer, Stuart, Schermer, Bernhard ORCID: 0000-0002-5194-9000, Benzing, Thomas and Brinkkoetter, Paul Thomas (2014). Breaking the chain at the membrane: paraoxonase 2 counteracts lipid peroxidation at the plasma membrane. Faseb J., 28 (4). S. 1769 - 1780. BETHESDA: FEDERATION AMER SOC EXP BIOL. ISSN 1530-6860

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Abstract

Lipid peroxidation through electrophilic molecules of extracellular origin is involved in the pathogenesis of many inflammatory conditions. To counteract free radical actions at the plasma membrane, cells host a variety of antioxidative enzymes. Here we analyzed localization, membrane topology, and trafficking of PON2 a member of the paraoxonase family of 3 enzymatically active proteins (PON1-3) found to have antiatherogenic properties. Immunohistochemistry localized PON2 to the villous tip of human intestinal epithelial cells. Employing membrane preparations, surface biotinylation experiments, and mutational analyses in HEK 293T and HeLa cells, we demonstrate that PON2 is a type II transmembrane protein. A hydrophobic stretch in the N terminus was identified as single transmembrane domain of PON2. The enzymatically active domain faced the extracellular compartment, where it suppressed lipid peroxidation (P < 0.05) and regulated the glucosylceramide content, as demonstrated by mass spectrometry (P < 0.05). PON2 translocation to the plasma membrane was dependent on intracellular calcium responses and could be induced to > 10-fold as compared to baseline (P=0.0001) by oxidative stress. Taken together, these data identify the paraoxonase protein PON2 as a type II transmembrane protein, which is dynamically translocated to the plasma membrane in response to oxidative stress to counteract lipid peroxidation.-Hagmann, H., Kuczkowski, A., Ruehl, M., Lamkemeyer, T., Brodesser, S., Horke, S., Dryer, S., Schermer, B., Benzing, T., Brinkkoetter, P. T. Breaking the chain at the membrane: paraoxonase 2 counteracts lipid peroxidation at the plasma membrane.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hagmann, Henning UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuczkowski, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Ruehl, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Lamkemeyer, Tobias UNSPECIFIED UNSPECIFIED UNSPECIFIED Brodesser, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Horke, Sven UNSPECIFIED UNSPECIFIED UNSPECIFIED Dryer, Stuart UNSPECIFIED UNSPECIFIED UNSPECIFIED Schermer, Bernhard UNSPECIFIED orcid.org/0000-0002-5194-9000 UNSPECIFIED Benzing, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Brinkkoetter, Paul Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-441215
DOI:	10.1096/fj.13-240309
Journal or Publication Title:	Faseb J.
Volume:	28
Number:	4
Page Range:	S. 1769 - 1780
Date:	2014
Publisher:	FEDERATION AMER SOC EXP BIOL
Place of Publication:	BETHESDA
ISSN:	1530-6860
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language LOW-DENSITY-LIPOPROTEIN; OXIDATIVE STRESS; ATHEROSCLEROSIS; DEFICIENCY; EXPRESSION; PRODUCTS; GENE; PHOSPHOLIPIDS; INFLAMMATION; MECHANISMS Multiple languages Biochemistry & Molecular Biology; Biology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44121