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免疫中的神经酰胺信号传导:分子视角

Ceramide signaling in immunity: a molecular perspective.

作者信息

Thakkar Himani, Vincent Vinnyfred, Chaurasia Bhagirath

机构信息

Division of Endocrinology, Department of Internal Medicine, Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA, USA.

出版信息

Lipids Health Dis. 2025 Jul 1;24(1):225. doi: 10.1186/s12944-025-02642-2.


DOI:10.1186/s12944-025-02642-2
PMID:40597360
Abstract

Ceramides are bioactive lipids that play a crucial role in cellular signaling and structural integrity (Nat Rev Mol Cell Biol 19:175-191, 2018). As members of the sphingolipid family, ceramides consist of a sphingoid base attached to a fatty acid (Annu Rev Biophys 47:633-654, 2018). Their unique structure confers both hydrophobic and amphipathic properties, enabling them to organize into membrane microdomains that influence cellular dynamics (Annu Rev Biophys 47:633-654, 2018). In recent years, ceramides have garnered attention for their role in modulating a range of cellular and organismal functions. Unlike other lipids that primarily serve structural roles, ceramides act as bioactive lipids in key signaling pathways, mediating stress responses such as inflammation, oxidative stress, growth inhibition, metabolism, autophagy, and apoptosis (J Lipid Res 60:913-918, 2019). Their regulatory effects are particularly important in immune cells, where ceramides can influence cell fate, modulate cellular metabolism, affect cytokine production, and dictate responses to external stimuli (Nature 510:58-67, 2014). Since ceramides maintain a dynamic equilibrium with other sphingolipids within a cell, understanding their role in immune cells in isolation provides only a partial perspective. Nevertheless, as a bioactive lipid and the central precursor of other sphingolipids, ceramides play a pivotal role in immune cells, deserving focused attention.

摘要

神经酰胺是具有生物活性的脂质,在细胞信号传导和结构完整性方面发挥着关键作用(《自然综述:分子细胞生物学》19:175 - 191, 2018)。作为鞘脂家族的成员,神经酰胺由一个连接脂肪酸的鞘氨醇碱基组成(《生物物理学年鉴》47:633 - 654, 2018)。它们独特的结构赋予了疏水和亲水两性特性,使它们能够组织成影响细胞动态的膜微区(《生物物理学年鉴》47:633 - 654, 2018)。近年来,神经酰胺因其在调节一系列细胞和机体功能中的作用而受到关注。与主要起结构作用的其他脂质不同,神经酰胺在关键信号通路中作为生物活性脂质发挥作用,介导炎症、氧化应激、生长抑制、代谢、自噬和凋亡等应激反应(《脂质研究杂志》60:913 - 918, 2019)。它们的调节作用在免疫细胞中尤为重要,在免疫细胞中神经酰胺可以影响细胞命运、调节细胞代谢、影响细胞因子产生并决定对外部刺激的反应(《自然》510:58 - 67, 2014)。由于神经酰胺在细胞内与其他鞘脂保持动态平衡,孤立地了解它们在免疫细胞中的作用仅提供了部分观点。然而,作为一种生物活性脂质和其他鞘脂的核心前体,神经酰胺在免疫细胞中起着关键作用,值得重点关注。

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本文引用的文献

[1]
Selective requirement of glycosphingolipid synthesis for natural killer and cytotoxic T cells.

Cell. 2025-6-26

[2]
The bioactive sphingolipid playbook. A primer for the uninitiated as well as sphingolipidologists.

J Lipid Res. 2025-6

[3]
Ceramide: a central regulator in Alzheimer's disease pathogenesis.

Inflammopharmacology. 2025-4

[4]
Ceramide mediates cell-to-cell ER stress transmission by modulating membrane fluidity.

J Cell Biol. 2025-5-5

[5]
Sensing ceramides by CYSLTR2 and P2RY6 to aggravate atherosclerosis.

Nature. 2025-5

[6]
The steady-state level of plasma membrane ceramide is regulated by neutral sphingomyelinase 2.

J Lipid Res. 2025-1

[7]
Neuroprotective effect of neuron-specific deletion of the C16 ceramide synthetic enzymes in an animal model of multiple sclerosis.

Glia. 2025-2

[8]
Ceramides-Emerging Biomarkers of Lipotoxicity in Obesity, Diabetes, Cardiovascular Diseases, and Inflammation.

Diseases. 2024-8-23

[9]
Alterations of ceramide synthesis induce PD-L1 internalization and signaling to regulate tumor metastasis and immunotherapy response.

Cell Rep. 2024-8-27

[10]
Ceramide-mediated orchestration of oxidative stress response through filopodia-derived small extracellular vesicles.

J Extracell Vesicles. 2024-7

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