Interaction of plasmenylcholine with free radicals in selected model systems

Broniec, Agnieszka; Żądło, Andrzej; Pawlak, Anna; Fuchs, Beate; Klosinski, Radoslaw; Thompson, David H.; Sarna, Tadeusz

doi:10.1016/j.freeradbiomed.2017.02.029

Cited by 21 publications

(17 citation statements)

References 45 publications

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“…Therefore, we propose that the increase in PUFA-containing lysoPCs is most likely due to high ROS production under high oxidative stress pathogenic conditions (APP WT/OSK overexpression). Increased lysoPL, particularly those containing PUFAs at the sn -2 position resulting from plasmalogen ( sn -1) phospholipid cleavage, is a well stablished oxidative stress signature [ 10 , 33 , 42 , 51 ]. Consistent with our proposed model, we found that the levels of 4-hydroxynonenal (4-HNE), a product of oxidative stress induced lipid peroxidation, were significantly increased in APP OSK mice compared to APP WT and non-Tg controls (by 66%, p = 0.04) (Fig.…”

Section: Resultsmentioning

confidence: 99%

Oligomeric amyloid-beta induces MAPK-mediated activation of brain cytosolic and calcium-independent phospholipase A2 in a spatial-specific manner

Palavicini

Wang

Chen

et al. 2017

acta neuropathol commun

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Alzheimer’s disease (AD) is histopathologically characterized by the build-up of fibrillar amyloid beta (Aβ) in the form of amyloid plaques and the development of intraneuronal neurofibrillary tangles consisting of aggregated hyperphosphorylated Tau. Although amyloid fibrils were originally considered responsible for AD pathogenesis, recent convincing evidence strongly implicates soluble oligomeric Aβ as the primary neurotoxic species driving disease progression. A third largely ignored pathological hallmark, originally described by Alois Alzheimer, is the presence of “adipose inclusions”, suggestive of aberrant lipid metabolism. The molecular mechanisms underlying these “lipoid granules”, as well as their potential link to soluble and/or fibrillar Aβ remain largely unknown. Seeking to better-understand these conundrums, we took advantage of the powerful technology of multidimensional mass spectrometry-based shotgun lipidomics and an AD transgenic mouse model overexpressing mutant amyloid precursor protein (APP E693Δ-Osaka-), where AD-like pathology and neurodegeneration occur as a consequence of oligomeric Aβ accumulation in the absence of amyloid plaques. Our results revealed for the first time that APP overexpression and oligomeric Aβ accumulation lead to an additive global accumulation of nonesterified polyunsaturated fatty acids (PUFAs) independently of amyloid plaques. Furthermore, we revealed that this accumulation is mediated by an increase in phospholipase A2 (PLA2) activity, evidenced by an accumulation of sn-1 lysophosphatidylcholine and by MAPK-mediated phosphorylation/activation of group IV Ca2+-dependent cytosolic (cPLA2) and the group VI Ca2+-independent PLA2 (iPLA2) independently of PKC. We further revealed that Aβ-induced oxidative stress also disrupts lipid metabolism via reactive oxygen species-mediated phospholipid cleavage leading to increased sn-2 lysophosphatidylcholine as well as lipid peroxidation and the subsequent accumulation of 4-hydroxynonenal. Brain histological studies implicated cPLA2 activity with arachidonic acid accumulation within myelin-rich regions, and iPLA2 activity with docosahexaenoic acid accumulation within pyramidal neuron-rich regions. Taken together, our results suggest that PLA2-mediated accumulation of free PUFAs drives AD-related disruption of brain lipid metabolism.

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Section: Resultsmentioning

confidence: 99%

Oligomeric amyloid-beta induces MAPK-mediated activation of brain cytosolic and calcium-independent phospholipase A2 in a spatial-specific manner

Palavicini

Wang

Chen

et al. 2017

acta neuropathol commun

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“…Paradoxically, pro-oxidant effects of these lipids have also been reported in a bulk lipid system (Wang and Wang, 2010 ). A recent study using synthetic choline plasmalogens in model membrane systems suggests that the antioxidant effect of plasmalogens occurs intramolecularly rather than intermolecularly and depends on the degree of unsaturation of the sn-1 and sn-2 chains, the length of these chains, and their conformation in membranes (Broniec et al, 2017 ). This suggests that the antioxidant capacity of plasmalogens may be contextually dependent.…”

Section: Biological Functions Of Ether Lipidsmentioning

confidence: 99%

Structural and functional roles of ether lipids

2017

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Ether lipids, such as plasmalogens, are peroxisome-derived glycerophospholipids in which the hydrocarbon chain at the sn-1 position of the glycerol backbone is attached by an ether bond, as opposed to an ester bond in the more common diacyl phospholipids. This seemingly simple biochemical change has profound structural and functional implications. Notably, the tendency of ether lipids to form non-lamellar inverted hexagonal structures in model membranes suggests that they have a role in facilitating membrane fusion processes. Ether lipids are also important for the organization and stability of lipid raft microdomains, cholesterol-rich membrane regions involved in cellular signaling. In addition to their structural roles, a subset of ether lipids are thought to function as endogenous antioxidants, and emerging studies suggest that they are involved in cell differentiation and signaling pathways. Here, we review the biology of ether lipids and their potential significance in human disorders, including neurological diseases, cancer, and metabolic disorders.

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“…Recent work with plasmenylcholine in model membrane systems resulted in the conclusion that the antioxidant action of plasmalogens occurs intramolecularly and is dependent on the sn‐2‐ esterified fatty acids. The authors question the role of plasmalogens as antoxidants in vivo . At this time it is difficult to know the reason for the retention of plasmalogens in contemporary anaerobic bacteria, which are presumably derived from some of the most ancient organisms on earth, when they were so readily dispensed with in the evolution of respiration.…”

Section: Comparison Of Fatty Aldehydes Derived From the Sn‐1 Alk‐1′‐ementioning

confidence: 99%

The anaerobic biosynthesis of plasmalogens

Goldfine

2017

FEBS Letters

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The biosynthesis of plasmalogens in anaerobic bacteria differs fundamentally from that in animal cells. Firstly, the formation of the alk-1 0 -enyl ether bond in animal cells is oxygen dependent. Secondly, the first step in plasmalogen formation in animal cells is an acylation of dihydroxyacetone phosphate, which has been ruled out as a precursor in anaerobes. In bacteria the alk-1 0 -enyl ether bond is formed after the fully formed acyl glycerolipids are synthesized. Evidence will be presented for the conversion of the sn-1 acyl-linked chain to an O-alk-1 0 -enyl ether by an as yet unknown mechanism.

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Interaction of plasmenylcholine with free radicals in selected model systems

Cited by 21 publications

References 45 publications

Oligomeric amyloid-beta induces MAPK-mediated activation of brain cytosolic and calcium-independent phospholipase A2 in a spatial-specific manner

Oligomeric amyloid-beta induces MAPK-mediated activation of brain cytosolic and calcium-independent phospholipase A2 in a spatial-specific manner

Structural and functional roles of ether lipids

The anaerobic biosynthesis of plasmalogens

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