Immune-related oxysterol modulates neuromuscular transmission via non-genomic liver X receptor-dependent mechanism

Zakyrjanova, Guzel F.; Tsentsevitsky, A. N.; Kuznetsova, Eva A.; Petrov, Alexey M.

doi:10.1016/j.freeradbiomed.2021.08.013

Cited by 16 publications

(8 citation statements)

References 51 publications

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“…In addition, 25-HC causes Ca 2+ -dependent increase in the intra-and extracellular levels of reactive oxygen species in the neuromuscular junctions. However, reactive oxygen species did not have a lipid-damaging eff ect, but contributed to the facilitation of neurotransmission [10]. It is interesting to note that despite the structural similarity to 25-HC, 24(S)-HC at a short-term application modulated neuromuscular transmission via an NMDAR-dependent but LXR-independent pathway [73,84].…”

Section: Hydroxycholesterol As a Molecule Of Intercellular Interacti...mentioning

confidence: 94%

“…25-HC is a strong natural activator of LXRs [3] present in the plasma membranes (lipid rafts) of some cells [82,83]. Recently, these receptors were found in the nerve terminals of motor neuron axons, where their distribution was depended on the integrity of lipid rafts [10]. The activation of synaptic LXRs by 25-HC increased the mobilization of synaptic vesicles stimulated by the release of Ca 2+ from the ER.…”

Section: Hydroxycholesterol As a Molecule Of Intercellular Interacti...mentioning

confidence: 99%

“…Moreover, EsRα is a potential target for 25-HC, and by stimulating it, 25-HC exhibits the estrogen-like activity in a number of cell types [9]. An increased mobilization of synaptic vesicles in the nerve terminals of motor neuron axons under the infl uence of 25-HC (see "Liver X receptors" section) also depends on EsRα [10]. Interestingly, in the central synapses, EsRα activation (with 17β-estradiol) can rapidly induce the long-term synaptic plasticity due to incorporation of additional glutamate AMPA receptors into the postsynaptic membrane [104].…”

Section: Hydroxycholesterol As a Molecule Of Intercellular Interacti...mentioning

confidence: 99%

“…Secondly, the main producers of 25-HC are macrophages (especially, alveolar macrophages [6]), dendritic cells, and microglia [3,4]. Thirdly, the targets of 25-HC include G protein-coupled receptors, transcription factors, adhesive molecules, and ion channels [3,[7][8][9][10]. As a hydroxycholesterol (HC), with a hydroxyl group in the side chain, 25-HC, can freely penetrate through plasma membranes and vascular barriers [11] and, therefore, act remotely as a para-and/or endocrine factor [12].…”

Section: Introductionmentioning

confidence: 99%

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25-Hydroxycholesterol as a Signaling Molecule of the Nervous System

Odnoshivkina

Kuznetsova

Petrov

2022

Biochemistry Moscow

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Cholesterol is an essential component of plasma membrane and precursor of biological active compounds, including hydroxycholesterols (HCs). HCs regulate cellular homeostasis of cholesterol; they can pass across the membrane and vascular barriers and act distantly as para-and endocrine agents. A small amount of 25-hydroxycholesterol (25-HC) is produced in the endoplasmic reticulum of most cells, where it serves as a potent regulator of the synthesis, intracellular transport, and storage of cholesterol. Production of 25-HC is strongly increased in the macrophages, dendrite cells, and microglia at the infl ammatory response. The synthesis of 25-HC can be also upregulated in some neurological disorders, such as Alzheimer's disease, amyotrophic lateral sclerosis, spastic paraplegia type 5, and X-linked adrenoleukodystrophy. However, it is unclear whether 25-HC aggravates these pathologies or has the protective properties. The molecular targets for 25-HC are transcriptional factors (LX receptors, SREBP2, ROR), G protein-coupled receptor (GPR183), ion channels (NMDA receptors, SLO1), adhesive molecules (α5β1 and ανβ3 integrins), and oxysterol-binding proteins. The diversity of 25-HC-binding proteins points to the ability of HC to aff ect many physiological and pathological processes. In this review, we focused on the regulation of 25-HC production and its universal role in the control of cellular cholesterol homeostasis, as well as the eff ects of 25-HC as a signaling molecule mediating the infl uence of infl ammation on the processes in the neuromuscular system and brain. Based on the evidence collected, it can be suggested that 25-HC prevents accumulation of cellular cholesterol and serves as a potent modulator of neuroinfl ammation, synaptic transmission, and myelinization. An increased production of 25-HC in response to a various type of damage can have a protective role and reduce neuronal loss. At the same time, an excess of 25-HC may exert the neurotoxic eff ects.

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Section: Hydroxycholesterol As a Molecule Of Intercellular Interacti...mentioning

confidence: 94%

Section: Hydroxycholesterol As a Molecule Of Intercellular Interacti...mentioning

confidence: 99%

Section: Hydroxycholesterol As a Molecule Of Intercellular Interacti...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

25-Hydroxycholesterol as a Signaling Molecule of the Nervous System

Odnoshivkina

Kuznetsova

Petrov

2022

Biochemistry Moscow

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“…In contrast with the traditional knowledge of LXRs' action on cell nucleus, these receptors can also have non-nuclear functions such as: LXRβ action on endothelial cells caveolae/lipid rafts that entails crosstalk with ERα, which promotes NO production and maintains endothelial monolayer integrity in vivo [43]; LXRβ expression in platelets (anucleate), being responsible for the inhibition of platelet function and thrombosis [44]; 25-hydroxycholesterol oxidant capacity and its regulatory action on synaptic vesicle mobilization via the activation of lipid raft-associated LXRs could trigger signaling via estrogen receptor α-Gi-protein-Gβγ-phospholipase C-Ca 2+ -protein kinase C pathway [45].…”

Section: Lxrmentioning

confidence: 99%

Effects of Oxysterols on Immune Cells and Related Diseases

Freitas

Levy

Reichert

et al. 2022

Cells

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Oxysterols are the products of cholesterol oxidation. They have a wide range of effects on several cells, organs, and systems in the body. Oxysterols also have an influence on the physiology of the immune system, from immune cell maturation and migration to innate and humoral immune responses. In this regard, oxysterols have been involved in several diseases that have an immune component, from autoimmune and neurodegenerative diseases to inflammatory diseases, atherosclerosis, and cancer. Here, we review data on the participation of oxysterols, mainly 25-hydroxycholesterol and 7α,25-dihydroxycholesterol, in the immune system and related diseases. The effects of these oxysterols and main oxysterol receptors, LXR and EBI2, in cells of the immune system (B cells, T cells, macrophages, dendritic cells, oligodendrocytes, and astrocytes), and in immune-related diseases, such as neurodegenerative diseases, intestinal diseases, cancer, respiratory diseases, and atherosclerosis, are discussed.

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Oxysterols in Central and Peripheral Synaptic Communication

Petrov

2023

Advances in Experimental Medicine and Biology

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Immune-related oxysterol modulates neuromuscular transmission via non-genomic liver X receptor-dependent mechanism

Cited by 16 publications

References 51 publications

25-Hydroxycholesterol as a Signaling Molecule of the Nervous System

25-Hydroxycholesterol as a Signaling Molecule of the Nervous System

Effects of Oxysterols on Immune Cells and Related Diseases

Oxysterols in Central and Peripheral Synaptic Communication

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