A simplified procedure for semi-targeted lipidomic analysis of oxidized phosphatidylcholines induced by UVA irradiation

Грубер, Флориан; Bicker, Wolfgang; Oskolkova, Olga; Tschachler, Erwin; Bochkov, Valery N.

doi:10.1194/jlr.d025270

Cited by 72 publications

(87 citation statements)

References 51 publications

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“…Other types of oxidized PC products, including the epoxyisoprostane PEIPC (m/z 828.6 > 184) and lysolipids such as 1-palmitoyl-2-hydroxylsn-glycero-3-phosphorylcholine m/z 496.3 > 184), have also been detected by SRM (18). More recently, an extensive list of SRM transitions was reported for the quantification of oxidized products derived from the most abundant species of phosphocholines in human dermal fibroblasts subjected to UVA irradiation, which clearly caused increased levels of many of these compounds (40). However, quite a few of these transitions were not specific for an individual oxidized product, owing to the existence of isobaric or isomeric PCs.…”

Section: Application Of Targeted Ms Methods For Oxidized Phospholipidsmentioning

confidence: 99%

Oxidative Lipidomics Coming of Age: Advances in Analysis of Oxidized Phospholipids in Physiology and Pathology

Spickett

Pitt

2015

Antioxidants & Redox Signaling

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Significance: Oxidized phospholipids are now well recognized as markers of biological oxidative stress and bioactive molecules with both pro-inflammatory and anti-inflammatory effects. While analytical methods continue to be developed for studies of generic lipid oxidation, mass spectrometry (MS) has underpinned the advances in knowledge of specific oxidized phospholipids by allowing their identification and characterization, and it is responsible for the expansion of oxidative lipidomics. Recent Advances: Studies of oxidized phospholipids in biological samples, from both animal models and clinical samples, have been facilitated by the recent improvements in MS, especially targeted routines that depend on the fragmentation pattern of the parent molecular ion and improved resolution and mass accuracy.

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Section: Application Of Targeted Ms Methods For Oxidized Phospholipidsmentioning

confidence: 99%

Oxidative Lipidomics Coming of Age: Advances in Analysis of Oxidized Phospholipids in Physiology and Pathology

Spickett

Pitt

2015

Antioxidants & Redox Signaling

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“…A lipid peroxidation chain reaction is initiated in cells by oxidation of membrane phospholipids that contain the bulk of cell-associated polyunsaturated fatty acids. Therefore, we analyzed the levels of oxidized phospholipids in the epidermis in vivo using mass spectrometry (23). We focused on phospholipid hydroperoxides, as some of these species had previously been identified as substrates of Prdx6 (29,30).…”

Section: Prdx6 Protects From Lipid Peroxidation In Vivomentioning

confidence: 99%

“…Epidermis was scraped off in 10 mL PBS/1 mmol/L EDTA/0.01% BHT, purged with argon, and frozen in liquid nitrogen. Analysis of oxidized phospholipids was conducted as previously described (23). For details, see Supplementary Information.…”

Section: Analysis Of Oxidized Phospholipidsmentioning

confidence: 99%

Dual Role of the Antioxidant Enzyme Peroxiredoxin 6 in Skin Carcinogenesis

et al. 2013

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The antioxidant enzyme peroxiredoxin 6 (Prdx6) is a key regulator of the cellular redox balance, particularly under stress conditions. We identified Prdx6 as an important player in different phases of skin carcinogenesis. Loss of Prdx6 in mice enhanced the susceptibility to skin tumorigenesis, whereas overexpression of Prdx6 in keratinocytes of transgenic mice had the opposite effect. The tumor-preventive effect of Prdx6, which was observed in a human papilloma virus 8-induced and a chemically induced tumor model, was not due to alterations in keratinocyte proliferation, apoptosis, or in the inflammatory response. Rather, endogenous and overexpressed Prdx6 reduced oxidative stress as reflected by the lower levels of oxidized phospholipids in the protumorigenic skin of Prdx6 transgenic mice and the higher levels in Prdx6-knockout mice than in control animals. In contrast to its beneficial effect in tumor prevention, overexpression of Prdx6 led to an acceleration of malignant progression of existing tumors, revealing a dual function of this enzyme in the pathogenesis of skin cancer. Finally, we found strong expression of PRDX6 in keratinocytes of normal human skin and in the tumor cells of squamous cell carcinomas, indicating a role of Prdx6 in human skin carcinogenesis. Taken together, our data point to the potential usefulness of Prdx6 activators or inhibitors for controlling different stages of skin carcinogenesis. Cancer Res; 73(11); 3460-9. Ó2013 AACR.

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“…More specifically, oxPAPC contains a mixture of oxidized phospholipids with various biological activities. Significant attention has been drawn to two major oxidation products of PAPC, 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) and 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) (15,19), which have been shown to disrupt the endothelial barrier (20) and to induce monocyte adhesion to endothelial cells (21). Notably, previous computational and experimental studies on model membranes indicate that incorporation of both POVPC and PGPC into single-component, unsaturated lipid bilayers changes the membrane structural properties and increases lipid mobility and diffusion (22).…”

Section: Introductionmentioning

confidence: 99%

Molecular-Scale Biophysical Modulation of an Endothelial Membrane by Oxidized Phospholipids

Ayee

LeMaster

Shentu

et al. 2017

Biophysical Journal

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The influence of two bioactive oxidized phospholipids on model bilayer properties, membrane packing, and endothelial cell biomechanics was investigated computationally and experimentally. The truncated tail phospholipids, 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) and 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC), are two major oxidation products of the unsaturated phospholipid 1-palmitoyl-2-arachidonoyl-sn-glycero-phosphocholine. A combination of coarse-grained molecular dynamics simulations, Laurdan multiphoton imaging, and atomic force microscopy microindentation experiments was used to determine the impact of POVPC and PGPC on the structure of a multicomponent phospholipid bilayer and to assess the consequences of their incorporation on membrane packing and endothelial cell stiffness. Molecular simulations predicted differential bilayer perturbation effects of the two oxidized phospholipids based on the chemical identities of their truncated tails, including decreased bilayer packing, decreased bilayer bending modulus, and increased water penetration. Disruption of lipid order was consistent with Laurdan imaging results indicating that POVPC and PGPC decrease the lipid packing of both ordered and disordered membrane domains. Computational predictions of a larger membrane perturbation effect by PGPC correspond to greater stiffness of PGPC-treated endothelial cells observed by measuring cellular elastic moduli using atomic force microscopy. Our results suggest that disruptions in membrane structure by oxidized phospholipids play a role in the regulation of overall endothelial cell stiffness.

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A simplified procedure for semi-targeted lipidomic analysis of oxidized phosphatidylcholines induced by UVA irradiation

Cited by 72 publications

References 51 publications

Oxidative Lipidomics Coming of Age: Advances in Analysis of Oxidized Phospholipids in Physiology and Pathology

Oxidative Lipidomics Coming of Age: Advances in Analysis of Oxidized Phospholipids in Physiology and Pathology

Dual Role of the Antioxidant Enzyme Peroxiredoxin 6 in Skin Carcinogenesis

Molecular-Scale Biophysical Modulation of an Endothelial Membrane by Oxidized Phospholipids

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