Compartmentalized regulation of lipid signaling in oxidative stress and inflammation: Plasmalogens, oxidized lipids and ferroptosis as new paradigms of bioactive lipid research

Astudillo, Alma M.; Balboa, Marı́a A.; Balsinde, Jesús

doi:10.1016/j.plipres.2022.101207

Cited by 32 publications

(26 citation statements)

References 202 publications

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“…In this study, we discovered a unique lipid molecule, ePLs, in neurons regulating sensory functions in Drosophila. ePLs have received increased attention due to their functional association with neurodegenerative diseases and metabolic disorders accompanied by systemic inflammation; potential roles such as being a scavenger of oxidative stress and a reservoir of fatty acid second messengers 40 , which could modulate the function of ion channels 41 , have been proposed. Recent studies have explored their involvement in ferroptosis and cancer treatment 42 .…”

Section: Discussionmentioning

confidence: 99%

“…The regulatory roles of ePLs on ion channel activity are open for discussion as there is a small number of studies available. Presence of PUFAs in the sn- 2 position of glycerol backbone in ePLs and their metabolites has been discussed as direct activators of ion channels 40 . Also, the ion transport activity of sarcosomal sodium–calcium exchanger was reported to be enhanced in plasmalogen-containing proteoliposome 43 .…”

Section: Discussionmentioning

confidence: 99%

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Ether phospholipids modulate somatosensory responses by tuning multiple receptor functions inDrosophila

Suito,

Nagao,

Deng

et al. 2023

Preprint

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Transient receptor potential (TRP) and PIEZO channels are known receptors for physical stimuli such as temperature and mechanical touch in sensory nerves. Since these receptors are localized in the plasma membrane, the regulation of sensory receptor activity by plasma membrane lipids has recently attracted attention. In this study, we focused on ether phospholipids (ePLs), which are abundant in neurons, and analyzed their role in somatosensation usingDrosophilaas a model. Reduced warmth avoidance was observed with ePL synthesizing gene knockout or knockdown in warmth-sensitive TRPA1-expressing neurons. The temperature threshold forDrosophilaTRPA1 channels significantly decreased in presence of ePLs. In addition, we found that ePLs modulate the mechanosensory behavior and activation properties of the mechanosensitive channel PIEZO. Finally, we revealed that ePLs affect physicochemical properties of the plasma membrane, such as membrane tension and lipid order, in culture cells. Our study identified ePLs as crucial regulators of multiple somatosensation modalities inDrosophila. Effects due to alteration of cellular membrane properties and activity modulation of sensory receptors.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Ether phospholipids modulate somatosensory responses by tuning multiple receptor functions inDrosophila

Suito,

Nagao,

Deng

et al. 2023

Preprint

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“…Unsurprisingly, PLA 2 enzymes are able to mobilize unique bioactive lipids in multiple ways that are spatiotemporally regulated, thus triggering distinct signaling pathways. In addition, an emerging concept in the control of the synthesis of oxygenated metabolites of AA—as well as other PUFAs—is the compartmentalization of the enzymes and lipid substrates within the cell, a clue that allows shaping the appropriate biological response in different cellular contexts [ 48 ]. Unfortunately, the molecular mechanisms that underlie the fine tuning of these enzymes, and their ability to drive signaling through one class of lipids or another, remain elusive.…”

Section: Interactions In Lipid Signaling Pathwaysmentioning

confidence: 99%

Deciphering Complex Interactions in Bioactive Lipid Signaling

Maccarrone

2023

Molecules

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Lipids are usually viewed as metabolic fuel and structural membrane components. Yet, in recent years, different families of lipids able to act as authentic messengers between cells and/or intracellularly have been discovered. Such lipid signals have been shown to exert their biological activity via specific receptors that, by triggering distinct signal transduction pathways, regulate manifold pathophysiological processes in our body. Here, endogenous bioactive lipids produced from arachidonic acid (AA) and other poly-unsaturated fatty acids will be presented, in order to put into better perspective the relevance of their mutual interactions for health and disease conditions. To this end, metabolism and signal transduction pathways of classical eicosanoids, endocannabinoids and specialized pro-resolving mediators will be described, and the intersections and commonalities of their metabolic enzymes and binding receptors will be discussed. Moreover, the interactions of AA-derived signals with other bioactive lipids such as shingosine-1-phosphate and steroid hormones will be addressed.

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“…Moreover, our previous study has reported that VSMC ferroptosis induced by high calcium and phosphate facilitates vascular calcification 28 . Additionally, ferroptosis involves extensive and rapid production of OxPLs, which can be induced by the reduction of glutathione‐based antioxidant mechanisms (such as GPX4) 29 . Notably, POVPC, one of the oxidized phospholipids, has been shown to induce ferroptosis in myocardial I/R injury 19 .…”

Section: Introductionmentioning

confidence: 99%

“…28 Additionally, ferroptosis involves extensive and rapid production of OxPLs, which can be induced by the reduction of glutathione-based antioxidant mechanisms (such as GPX4). 29 Notably, POVPC, one of the oxidized phospholipids, has been shown to induce ferroptosis in myocardial I/R injury. 19 However, the relationship between POVPC and ferroptosis in the process of vascular calcification has not been studied before.…”

Section: Introductionmentioning

confidence: 99%

Oxidized phospholipid POVPC contributes to vascular calcification by triggering ferroptosis of vascular smooth muscle cells

Lu,

Ye,

Chen

et al. 2024

The FASEB Journal

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Vascular calcification is an actively regulated biological process resembling bone formation, and osteogenic differentiation of vascular smooth muscle cells (VSMCs) plays a crucial role in this process. 1‐Palmitoyl‐2‐(5′‐oxo‐valeroyl)‐sn‐glycero‐3‐phosphocholine (POVPC), an oxidized phospholipid, is found in atherosclerotic plaques and has been shown to induce oxidative stress. However, the effects of POVPC on osteogenic differentiation and calcification of VSMCs have yet to be studied. In the present study, we investigated the role of POVPC in vascular calcification using in vitro and ex vivo models. POVPC increased mineralization of VSMCs and arterial rings, as shown by alizarin red staining. In addition, POVPC treatment increased expression of osteogenic markers Runx2 and BMP2, indicating that POVPC promotes osteogenic transition of VSMCs. Moreover, POVPC increased oxidative stress and impaired mitochondria function of VSMCs, as shown by increased ROS levels, impairment of mitochondrial membrane potential, and decreased ATP levels. Notably, ferroptosis triggered by POVPC was confirmed by increased levels of intracellular ROS, lipid ROS, and MDA, which were decreased by ferrostatin‐1, a ferroptosis inhibitor. Furthermore, ferrostatin‐1 attenuated POVPC‐induced calcification of VSMCs. Taken together, our study for the first time demonstrates that POVPC promotes vascular calcification via activation of VSMC ferroptosis. Reducing the levels of POVPC or inhibiting ferroptosis might provide a novel strategy to treat vascular calcification.

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Compartmentalized regulation of lipid signaling in oxidative stress and inflammation: Plasmalogens, oxidized lipids and ferroptosis as new paradigms of bioactive lipid research

Cited by 32 publications

References 202 publications

Ether phospholipids modulate somatosensory responses by tuning multiple receptor functions inDrosophila

Ether phospholipids modulate somatosensory responses by tuning multiple receptor functions inDrosophila

Deciphering Complex Interactions in Bioactive Lipid Signaling

Oxidized phospholipid POVPC contributes to vascular calcification by triggering ferroptosis of vascular smooth muscle cells

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