25-Hydroxycholesterol
(Synonyms: 25-羟基胆固醇) 目录号 : GC33860
25-羟基胆固醇是胆固醇代谢生成的一种侧链氧甾醇，由巨噬细胞响应 Toll 样受体(TLR)激活分泌。
Cas No.:2140-46-7
Sample solution is provided at 25 µL, 10mM.
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- Purity: >98.00%
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- Datasheet
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Cell experiment [1]: |
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Cell lines |
splenic B220+ cells |
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Preparation method |
Treated cells were diluted to 1×105 cells per well (96-well plate) into medium containing the indicated cytokines (TGF-β1, IL-5, and IL-2) with or without 25-Hydroxycholesterol (250 nM) in triplicate. B cells were grown for an additional 6 days and cells and medium harvested. |
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Reaction Conditions |
250 nM; 6 days |
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Applications |
25-Hydroxycholesterol inhibited IgA secretion when measured on day 6, but had no effect when added on days 4 and 5. |
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Animal experiment [2]: |
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Animal models |
Ch25h–/– mice |
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Preparation method |
mice were treated i.p. with 50 mg/kg 25-Hydroxycholesterol or vehicle (hydroxypropyl beta cyclodextrin) daily for 3 days with sacrifice 4 hours after the final dose. |
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Dosage form |
50 mg/kg; i.p. |
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Applications |
25-Hydroxycholesterol upregulated Chop and the additional ER stress markers BiP and Atf4 in the lungs of naive Ch25h–/– mice. |
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References: [1] Bauman D R , Bitmansour A D , Mcdonald J G ,et al. 25-Hydroxycholesterol secreted by macrophages in response to Toll-like receptor activation suppresses immunoglobulin A production[J].Proceedings of the National Academy of Sciences, 2009, 106(39):16764-16769. [2] Madenspacher JH, Morrell ED, McDonald JG, et al. 25-Hydroxycholesterol exacerbates vascular leak during acute lung injury[J]. JCI Insight. 2023 10;8(7):e155448. |
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25-hydroxycholesterol is a side-chain oxysterol produced by cholesterol metabolism and secreted by macrophages in response to Toll-like receptor (TLR) activation. 25-hydroxycholesterol effectively and selectively inhibits IgA production by B cells, with an EC50 of approximately 65nM[1]. 25-hydroxycholesterol directly regulates lipid metabolism and inflammatory response in hepatocytes through LXR/SREBP-1 and IκBα/NFκB signaling[2]. 25-hydroxycholesterol has antiviral effects and can also regulate transcriptional responses through AP-1 and act as an inflammatory amplifier [3].
In vitro, 25-hydroxycholesterol (5μM) stimulated mouse macrophages for 18 hours, and RNA expression was analyzed by microarray and seven members of the AP-1 family (Fos, Fosb, Fosl1, Fosl2, Jun, Junb, and Jund) was significantly up-regulated[3]. Treatment of splenic B220+ cells with 25-hydroxycholesterol (250 nM) for 6 days resulted in CSR inhibition, thereby inhibiting IgA secretion, but addition on days 4 and 5 had no effect because of the occurrence of Ig heavy chain site rearrangement[4]. 25-hydroxycholesterol (10−4, 10−5 and 10−6M) dose-dependently inhibits the growth of sparse smooth muscle cells in ethanol vehicles [5].
In vivo, 25-hydroxycholesterol (50 mg/kg; i.p.) upregulates Chop in the lungs of Ch25h–/– mice, as well as the endoplasmic reticulum stress markers BiP and Atf4 [6]. 25-hydroxycholesterol (1.5mg/kg; i.v.) can protect rhesus monkeys from ZIKV virus infection, and 25-hydroxycholesterol (50mg/kg; i.p.) can also prevent ZIKV infection in mice and prevent microcephaly symptoms [7] .
References:
[1] McDonald JG, et al. Editorial: 25-Hydroxycholesterol: a new life in immunology[J]. J Leukoc Biol. 2010 Dec;88(6):1071-1072.
[2] Xu L , Bai Q , Rodriguez-Agudo D ,et al. Regulation of Hepatocyte Lipid Metabolism and Inflammatory Response by 25-Hydroxycholesterol and 25-Hydroxycholesterol-3-sulfate[J]. Lipids, 2010, 45(9): 821–832.
[3]Elizabeth S. Gold, Alan H. Diercks, Irina Podolsky, et al. 25-Hydroxycholesterol acts as an amplifier of inflammatory signaling[J]. PNAS, 2014,111 (29):10666-10671.
[4] Bauman D R , Bitmansour A D , Mcdonald J G ,et al.25-Hydroxycholesterol secreted by macrophages in response to Toll-like receptor activation suppresses immunoglobulin A production[J].Proceedings of the National Academy of Sciences, 2009, 106(39):16764-16769.
[5]Cox D C , Comi K , Goldstein A L .Effects of cholesterol and 25-hydroxycholesterol on smooth muscle cell and endothelial cell growth[J].Lipids, 1988, 23(2):85-88.
[6]Madenspacher JH, Morrell ED, McDonald JG, et al. 25-Hydroxycholesterol exacerbates vascular leak during acute lung injury[J]. JCI Insight. 2023 10;8(7):e155448.
[7]Li C , Deng Y Q , Wang S ,et al.25-Hydroxycholesterol Protects Host against Zika Virus Infection and Its Associated Microcephaly in a Mouse Model.[J].Immunity, 2017, 46(3):446.
25-羟基胆固醇是胆固醇代谢生成的一种侧链氧甾醇，由巨噬细胞响应 Toll 样受体(TLR)激活分泌。25-羟基胆固醇有效且选择性抑制B细胞产生 IgA，EC50 约为65 nM[1]。25-羟基胆固醇通过LXR/SREBP-1和IκBα/NFκB信号直接调节肝细胞的脂质代谢和炎症反应[2]。25-羟基胆固醇具有抗病毒作用，还可以通过AP-1调节转录反应并作为炎症放大器[3]。
在体外，25-羟基胆固醇（5 μM）刺激小鼠巨噬细胞18 小时，并通过微阵列分析RNA表达，发现AP-1家族的7个成员（Fos、Fosb、Fosl1、Fosl2、Jun、Junb 和 Jund）显著上调[3]。25-羟基胆固醇（250 nM）处理脾B220 + 细胞6天，会导致CSR抑制，从而抑制了IgA的分泌，但在第4天和第5天添加则没有影响，因为 Ig重链位点发生了重排[4]。25-羟基胆固醇（10−4、10−5 和 10−6 M）在乙醇载体中剂量依赖性地抑制稀疏平滑肌细胞的生长[5]。
在体内，25-羟基胆固醇（50 mg/kg; i.p.）上调了Ch25h–/–小鼠肺部的Chop，以及内质网应激标记物BiP和Atf4[6]。25-羟基胆固醇（1.5mg/kg; i.v.）能保护恒河猴免受ZIKV病毒感染，25-羟基胆固醇（50mg/kg; i.p.）也能阻止ZIKV感染小鼠，防止小头畸形症状[7]。
| Cas No. | 2140-46-7 | SDF | |
| 别名 | 25-羟基胆固醇 | ||
| 化学名 | cholest-5-ene-3β,25-diol | ||
| Canonical SMILES | CC(C)(O)CCC[C@@H](C)[C@H]1CC[C@@]2([H])[C@]3([H])CC=C4C[C@@H](O)CC[C@]4(C)[C@@]3([H])CC[C@]12C | ||
| 分子式 | C27H46O2 | 分子量 | 402.65 |
| 溶解度 | 20mg/mL in ethanol, 2mg/mL in DMF, 5mg/mL in DMSO (Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4835 mL | 12.4177 mL | 24.8355 mL |
| 5 mM | 0.4967 mL | 2.4835 mL | 4.9671 mL |
| 10 mM | 0.2484 mL | 1.2418 mL | 2.4835 mL |
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动物平均体重 | g | |
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动物数量 | 只 |
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25-Hydroxycholesterol-Induced Oxiapoptophagy in L929 Mouse Fibroblast Cell Line
Molecules 2021 Dec 29;27(1):199.PMID:35011433DOI:10.3390/molecules27010199.
25-Hydroxycholesterol (25-HC) is an oxysterol synthesized from cholesterol by cholesterol-25-hydroxylase during cholesterol metabolism. The aim of this study was to verify whether 25-HC induces oxiapoptophagy in fibroblasts. 25-HC not only decreased the survival of L929 cells, but also increased the number of cells with condensed chromatin and altered morphology. Fluorescence-activated cell sorting results showed that there was a dose-dependent increase in the apoptotic populations of L929 cells upon treatment with 25-HC. 25-HC-induced apoptotic cell death was mediated by the death receptor-dependent extrinsic and mitochondria-dependent intrinsic apoptosis pathway, through the cascade activation of caspases including caspase-8, -9, and -3 in L929 cells. There was an increase in the levels of reactive oxygen species and inflammatory mediators such as inducible nitric oxide synthase, cyclooxygenase-2, nitric oxide, and prostaglandin E2 in L929 cells treated with 25-HC. Moreover, 25-HC caused an increase in the expression of beclin-1 and microtubule-associated protein 1A/1B-light chain 3, an autophagy biomarker, in L929 cells. There was a significant decrease in the phosphorylation of protein kinase B (Akt) in L929 cells treated with 25-HC. Taken together, 25-HC induced oxiapoptophagy through the modulation of Akt and p53 cellular signaling pathways in L929 cells.
25-Hydroxycholesterol as a Signaling Molecule of the Nervous System
Biochemistry (Mosc) 2022 Jun;87(6):524-537.PMID:35790411DOI:10.1134/S0006297922060049.
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 inflammatory 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 affect 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 effects of 25-HC as a signaling molecule mediating the influence of inflammation 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 neuroinflammation, 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 effects.
The cholesterol metabolite 25-Hydroxycholesterol restrains the transcriptional regulator SREBP2 and limits intestinal IgA plasma cell differentiation
Immunity 2021 Oct 12;54(10):2273-2287.e6.PMID:34644558DOI:10.1016/j.immuni.2021.09.004.
Diets high in cholesterol alter intestinal immunity. Here, we examined how the cholesterol metabolite 25-Hydroxycholesterol (25-HC) impacts the intestinal B cell response. Mice lacking cholesterol 25-hydroxylase (CH25H), the enzyme generating 25-HC, had higher frequencies of immunoglobulin A (IgA)-secreting antigen-specific B cells upon immunization or infection. 25-HC did not affect class-switch recombination but rather restrained plasma cell (PC) differentiation. 25-HC was produced by follicular dendritic cells and increased in response to dietary cholesterol. Mechanistically, 25-HC restricted activation of the sterol-sensing transcription factor SREBP2, thereby regulating B cell cholesterol biosynthesis. Ectopic expression of SREBP2 in germinal center B cells induced rapid PC differentiation, whereas SREBP2 deficiency reduced PC output in vitro and in vivo. High-cholesterol diet impaired, whereas Ch25h deficiency enhanced, the IgA response against Salmonella and the resulting protection from systemic bacterial dissemination. Thus, a 25-HC-SREBP2 axis shapes the humoral response at the intestinal barrier, providing insight into the effect of high dietary cholesterol in intestinal immunity.
Interferon-inducible cholesterol-25-hydroxylase broadly inhibits viral entry by production of 25-Hydroxycholesterol
Immunity 2013 Jan 24;38(1):92-105.PMID:23273844DOI:10.1016/j.immuni.2012.11.005.
Interferons (IFN) are essential antiviral cytokines that establish the cellular antiviral state through upregulation of hundreds of interferon-stimulated genes (ISGs), most of which have uncharacterized functions and mechanisms. We identified cholesterol-25-hydroxylase (CH25H) as a broadly antiviral ISG. CH25H converts cholesterol to a soluble antiviral factor, 25-Hydroxycholesterol (25HC). 25HC treatment in cultured cells broadly inhibited growth of enveloped viruses including VSV, HSV, HIV, and MHV68 and acutely pathogenic EBOV, RVFV, RSSEV, and Nipah viruses under BSL4 conditions. It suppressed viral growth by blocking membrane fusion between virus and cell. In animal models, Ch25h-deficient mice were more susceptible to MHV68 lytic infection. Moreover, administration of 25HC in humanized mice suppressed HIV replication and reversed T cell depletion. Thus, our studies demonstrate a unique mechanism by which IFN achieves its antiviral state through the production of a natural oxysterol to inhibit viral entry and implicate membrane-modifying oxysterols as potential antiviral therapeutics.
Pathogenic role of 25-Hydroxycholesterol in cancer development and progression
Future Oncol 2022 Dec;18(39):4415-4442.PMID:36651359DOI:10.2217/fon-2022-0819.
Cholesterol is an essential lipid that serves several important functions, including maintaining the homeostasis of cells, acting as a precursor to bile acid and steroid hormones and preserving the stability of membrane lipid rafts. 25-Hydroxycholesterol (25-HC) is a cholesterol derivative that may be formed from cholesterol. 25-HC is a crucial component in various biological activities, including cholesterol metabolism. In recent years, growing evidence has shown that 25-HC performs a critical function in the etiology of cancer, infectious diseases and autoimmune disorders. This review will summarize the latest findings regarding 25-HC, including its biogenesis, immunomodulatory properties and role in innate/adaptive immunity, inflammation and the development of various types of cancer.