Interactions between phospholipids, saccharides and oxidized lipids in non-enzymic browning reactions

Oxidized lipids are capable of initiating diverse cellular responses through both receptor-mediated mechanisms and direct posttranslational modification of proteins. Typically, exposure of cells to low concentrations of oxidized lipids induces cytoprotective pathways, whereas high concentrations result in apoptosis. Interestingly, mitochondria can contribute to processes that result in either cytoprotection or cell death. The role of antioxidant defenses such as glutathione in adaptation to stress has been established, but the potential interaction with mitochondrial function is unknown and is examined in this article. Human umbilical vein endothelial cells (HUVEC) were exposed to oxidized LDL (oxLDL) or the electrophilic cyclopentenone 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2). We demonstrate that complex I activity, but not citrate synthase or cytochrome- c oxidase, is significantly induced by oxLDL and 15d-PGJ2. The mechanism is not clear at present but is independent of the induction of GSH, peroxisome proliferator-activated receptor (PPAR)-γ, and PPAR-α. This response is dependent on the induction of oxidative stress in the cells because it can be prevented by nitric oxide, probucol, and the SOD mimetic manganese(III) tetrakis(4-benzoic acid) porphyrin chloride. This increased complex I activity appears to contribute to protection against apoptosis induced by 4-hydroxynonenal.

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Abstract 30: Localized Immune Response to Oxidized Lipids in ABCG1-/- Mice: A New Model for Lipid-Driven Autoimmunity

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.34.suppl_1.30 ◽

2014 ◽

Vol 34 (suppl_1) ◽

Author(s):

Angel Baldan ◽

Ayelet Gonen ◽

Christina Choung ◽

Tyler Marquart ◽

Xuchu Que ◽

...

Keyword(s):

Immune Response ◽

B Cells ◽

Lipid Accumulation ◽

Cell Activation ◽

Metabolic Diseases ◽

Oxidized Lipids ◽

B Cell Activation ◽

Crystal Deposition ◽

New Model ◽

Atherosclerotic Lesions

Many metabolic diseases, including atherosclerosis, type 2 diabetes, pulmonary alveolar proteinosis (PAP), and obesity, have a chronic inflammatory component involving both innate and adaptive immunity. Mice lacking the ATP binding cassette (ABC) transporter ABCG1, develop chronic inflammation in the lungs, associated with lipid accumulation (cholesterol, cholesterol ester, phospholipid, oxidized lipids) and cholesterol crystal deposition, characteristic of atherosclerotic lesions and PAP. Here we demonstrate that specific lipids, likely oxidized (Ox) phospholipids and/or sterols, elicit a lung-specific immune response in Abcg1-/- mice. Loss of ABCG1 results in increased levels of specific oxysterols, phosphatidylcholines and oxidized phospholipids, including 1-palmitoyl-2-(5’-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC), in the lungs. Further, we identify a niche-specific increase in natural antibody (NAb)-secreting B-1 B cells in response to this lipid accumulation that is paralleled by increased titers of IgM, IgA and IgG against oxidation specific epitopes such as those on OxLDL and malondialdehyde-modified LDL (MDA-LDL). Finally, we identify a cytokine/chemokine signature in the lungs of Abcg1-/- mice reflective of increased B cell activation, antibody secretion and homing. Collectively, these data demonstrate that the accumulation of lipids in Abcg1-/- mice induces the specific expansion and localization of B-1 B cells, which secrete NAbs that may help protect against the development of atherosclerosis. Indeed, despite chronic lipid accumulation and inflammation, hyperlipidemic mice lacking ABCG1 develop smaller atherosclerotic lesions compared to controls. These data also suggest that Abcg1-/- mice may represent a new model in which to study the protective functions of B-1 B cells/NAbs, and may provide novel targets for pharmacologic intervention and treatment of disease.

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Structural and dynamic effects of oxidized lipids in unsaturated lipid membranes

Free Radical Biology and Medicine ◽

10.1016/0891-5849(90)90618-s ◽

1990 ◽

Vol 9 ◽

pp. 124 ◽

Cited By ~ 1

Author(s):

M.L. Wratten ◽

A.A. van't Veld ◽

U.A. van der Heide ◽

G. van Ginkel ◽

A. Sevanian ◽

...

Keyword(s):

Lipid Membranes ◽

Oxidized Lipids ◽

Dynamic Effects ◽

Unsaturated Lipid

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Blood Exosomes Have Neuroprotective Effects in a Mouse Model of Parkinson’s Disease

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/3807476 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14

Author(s):

Ting Sun ◽

Zhe-Xu Ding ◽

Xin Luo ◽

Qing-Shan Liu ◽

Yong Cheng

Keyword(s):

Oxidative Stress ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Amino Acid ◽

Dopaminergic Neurons ◽

Motor Coordination ◽

Oxidized Lipids ◽

Metabolomic Analysis ◽

Neuroprotective Effects ◽

And Control

Parkinson’s disease (PD) is a common and complex neurodegenerative disease; the pathogenesis of which is still uncertain. Exosomes, nanosized extracellular vesicles, have been suggested to participate in the pathogenesis of PD, but their role is unknown. Here, a metabolomic analysis of serum and brain exosomes showed differentially expressed metabolites between 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride- (MPTP-) induced PD mice and control mice, such as oxidized lipids, vitamins, and cholesterol. These metabolites were enriched in coenzyme, nicotinamide, and amino acid pathways related to PD, and they could be served as preclinical biomarkers. We further found that blood-derived exosomes from healthy volunteers alleviated impaired motor coordination in MPTP-treated mice. Results from immunohistochemistry and western blotting indicated that the loss of dopaminergic neurons in substantia nigra and striatum of PD model mice was rescued by the exosome treatment. The exosome treatment also restored the homeostasis of oxidative stress, neuroinflammation, and cell apoptosis in the model mice. These results suggest that exosomes are important mediators for PD pathogenesis, and exosomes are promising targets for the diagnosis and treatment of PD.

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