24-Hydroxycholesterol
(Synonyms: 24-羟基胆固醇) 目录号 : GC33673
24-Hydroxycholesterol是一种天然的固醇类物质，是n-甲基-d-天门冬氨酸受体(NMDA)和转录因子LXR的激活剂。
Cas No.:30271-38-6
Sample solution is provided at 25 µL, 10mM.
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24-Hydroxycholesterol is a natural sterol, which serves as a positive allosteric modulator of N-Methyl-d-Aspartate (NMDA) receptorsR, and a potent activator of the transcription factors LXR.
24S-hydroxycholesterol oxysterol-generating enzyme Cyp46a1 is overexpressed during the angiogenic switch in rat insulin promoter 1-T-antigen 2 (RIP1-Tag2) pNET formation[1].
Hypoxia inducible factor-1a (HIF-1α) controls the overexpression of the enzyme Cyp46a1, which generates the oxysterol 24-hydroxycholesterol in a pancreatic neuroendocrine tumor (pNET) model commonly used to study neoangiogenesis. The activation of the HIF-1α-24S-HC axis ultimately leads to the induction of the angiogenic switch through the positioning of proangiogenic neutrophils in proximity to Cyp46a1+ islets[1]. 24-hydroxycholesterol levels are increased at 2-4 months in the untreated 5XFAD mouse brain and then became similar to those in the B6SJL mouse brain[2].
[1]. Soncini M, et al. 24-Hydroxycholesterol participates in pancreatic neuroendocrine tumor development. Proc Natl Acad Sci U S A. 2016 Oct 11;113(41):E6219-E6227. Epub 2016 Sep 26. [2]. Mast N, et al. Cholesterol-metabolizing enzyme cytochrome P450 46A1 as a pharmacologic target for Alzheimer's disease. Neuropharmacology. 2017 Sep 1;123:465-476.
| Cas No. | 30271-38-6 | SDF | |
| 别名 | 24-羟基胆固醇 | ||
| Canonical SMILES | CC(C)C(O)CC[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 | Soluble in DMSO | 储存条件 | Store at -20°C |
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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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Cholesterol, 24-Hydroxycholesterol, and 27-Hydroxycholesterol as Surrogate Biomarkers in Cerebrospinal Fluid in Mild Cognitive Impairment and Alzheimer's Disease: A Meta-Analysis
J Alzheimers Dis 2016;51(1):45-55.PMID:26836015DOI:10.3233/JAD-150734.
Abnormal cholesterol metabolism is an established feature of Alzheimer's disease (AD). Cerebrospinal fluid (CSF) is the fluid surrounding the central nervous system, and the protein and lipid content alterations in the CSF could be biomarkers for degenerative changes in the brain. The laboratory diagnosis of AD is limited to the analysis of three biomarkers in CSF: Aβ42, total tau, and phospho-tau. The purpose of this analysis is to systematically analyze the available data describing the biomarkers of cholesterol and its metabolites in the CSF of subjects with AD. MEDLINE, EMBASE, and the Cochrane Central database were systematically queried to collect studies that have evaluated the markers of cholesterol and its metabolites in the CSF of subjects with mild cognitive impairment (MCI) or AD and age-matched controls. Analysis of the published data shows that the levels of cholesterol are increased in MCI subjects; 24-Hydroxycholesterol and 27-hydroxycholesterol are elevated in AD and MCI subjects compared to controls. There is a significant dysfunction of cholesterol metabolism in the CSF of AD subjects. This analysis indicates that in addition to the available biomarkers in the CSF, such as Aβ42, total tau, and phospho-tau, 24-Hydroxycholesterol, 27-hydroxycholesterol, and cholesterol appear to be sensitive biomarkers for the evaluation of MCI and AD.
24-Hydroxycholesterol Induces Tau Proteasome-Dependent Degradation via the SIRT1/PGC1α/Nrf2 Pathway: A Potential Mechanism to Counteract Alzheimer's Disease
Antioxidants (Basel) 2023 Mar 3;12(3):631.PMID:36978879DOI:10.3390/antiox12030631.
Considerable evidence indicates that cholesterol oxidation products, named oxysterols, play a key role in several events involved in Alzheimer's disease (AD) pathogenesis. Although the majority of oxysterols causes neuron dysfunction and degeneration, 24-Hydroxycholesterol (24-OHC) has recently been thought to be neuroprotective also. The present study aimed at supporting this concept by exploring, in SK-N-BE neuroblastoma cells, whether 24-OHC affected the neuroprotective SIRT1/PGC1α/Nrf2 axis. We demonstrated that 24-OHC, through the up-regulation of the deacetylase SIRT1, was able to increase both PGC1α and Nrf2 expression and protein levels, as well as Nrf2 nuclear translocation. By acting on this neuroprotective pathway, 24-OHC favors tau protein clearance by triggering tau ubiquitination and subsequently its degradation through the ubiquitin-proteasome system. We also observed a modulation of SIRT1, PGC1α, and Nrf2 expression and synthesis in the brain of AD patients with the progression of the disease, suggesting their potential role in neuroprotection. These findings suggest that 24-OHC contributes to tau degradation through the up-regulation of the SIRT1/PGC1α/Nrf2 axis. Overall, the evidence points out the importance of avoiding 24-OHC loss, which can occur in the AD brain, and of limiting SIRT1, PGC1α, and Nrf2 deregulation in order to prevent the neurotoxic accumulation of hyperphosphorylated tau and counteract neurodegeneration.
Serum 24-Hydroxycholesterol in probable Alzheimer's dementia: Reexploring the significance of a tentative Alzheimer's disease biomarker
Aging Med (Milton) 2019 May 25;2(2):74-81.PMID:31942515DOI:10.1002/agm2.12068.
Objective: This study measured and analyzed the serum levels of 24-Hydroxycholesterol in patients with probable Alzheimer's disease (AD) and age-/sex-matched controls. Methods: A case-control study involving 40 AD patients and 40 controls was performed at a tertiary neurological teaching hospital in eastern India. Blood and serum samples were collected for APOE genotyping and 24-Hydroxycholesterol levels, respectively. Results: Serum 24-Hydroxycholesterol was significantly lower in AD patients compared to controls (median concentration: controls, 47.14 ng/mL (interquartile range, 16.34); AD patients, 32.93 ng/mL (interquartile range, 9.45); P < 0.001) but showed no significant correlation with Mini Mental State Examination (MMSE) score in AD cases (r = -0.169, P = 0.298) or in controls (r = 0.18, P = 0.26). No statistically significant difference was observed between serum 24-Hydroxycholesterol levels of the APOE4-positive and -negative subgroups in AD patients (P = 0.79). Findings were consistent and unchanged even when the ratio of serum 24-Hydroxycholesterol to serum total cholesterol was considered. Conclusion: The decreased 24-Hydroxycholesterol level in peripheral circulation in AD cases observed in the present study may suggest its role in AD pathogenesis. The lack of a clear correlation between serum levels of 24-Hydroxycholesterol and MMSE score-a surrogate marker of AD severity-raises the question as to whether 24-Hydroxycholesterol level declines with decreasing neuronal mass or whether the steroid continues to play a protective role.
Plasma 24-Hydroxycholesterol is associated with narrower common carotid artery and greater flow velocities in relapsing multiple sclerosis
Mult Scler Relat Disord 2022 Jul;63:103906.PMID:35671670DOI:10.1016/j.msard.2022.103906.
Background: Multiple sclerosis (MS) studies suggest greater cardiovascular disease burden and disturbances in the cholesterol pathways. The potential impact of oxidized cholesterol molecules on MS is emerging. Objective: To determine the relationship between multiple oxysterol molecules and atherosclerosis burden in MS patients. Materials and methods: A total of 99 MS patients (61 relapsing-remitting MS(RRMS) and 38 progressive MS (PMS)) patients and 38 healthy controls (HCs) underwent magnetic resonance angiography (MRA) and the cross-sectional area (CSA) of the common carotid artery (CCA) was determined at three different levels before the bifurcation (C7, C6 and C5). Additionally, an echo-color Doppler ultrasound was performed and measures of blood flow velocities were derived. Blood samples acquired at the time of the imaging examinations were analyzed and 24-, 25-, 27-hydroxycholesterol (24HC, 25HC, 27HC) and 7-ketocholesterol (7KC) were quantified in ng/mL RESULTS: In the MS patients, higher levels of 24HC were significantly associated with smaller CCA CSA measured at all three cervical levels (r=-0.201, p = 0.046; r=-0.228, p = 0.023, and r=-0.215, p = 0.032, for C7, C6 and C5, respectively). These associations were driven by the RRMS group only (r=-0.407, p = 0.002 for C7; r=-0.414, p = 0.002, for C6; and r=-0.368, p = 0.006 for C5). No associations were seen in the HCs. Despite adjusting for the significant age effect (B = 0.445, p = 0.004), higher 24HC levels were independently associated with smaller CCA CSA (B=-0.20, p = 0.045). 24HC was additionally associated with greater time-averaged and peak diastolic CCA velocities. RRMS patients treated with potent anti-inflammatory therapies had lower oxysterol levels (p = 0.019). Conclusion: Greater 24HC levels are associated with smaller CSA CCA and greater flow velocities in RRMS patients.
24-Hydroxycholesterol participates in pancreatic neuroendocrine tumor development
Proc Natl Acad Sci U S A 2016 Oct 11;113(41):E6219-E6227.PMID:27671648DOI:10.1073/pnas.1613332113.
Cells in the tumor microenvironment may be reprogrammed by tumor-derived metabolites. Cholesterol-oxidized products, namely oxysterols, have been shown to favor tumor growth directly by promoting tumor cell growth and indirectly by dampening antitumor immune responses. However, the cellular and molecular mechanisms governing oxysterol generation within tumor microenvironments remain elusive. We recently showed that tumor-derived oxysterols recruit neutrophils endowed with protumoral activities, such as neoangiogenesis. Here, we show that hypoxia inducible factor-1a (HIF-1α) controls the overexpression of the enzyme Cyp46a1, which generates the oxysterol 24-Hydroxycholesterol (24S-HC) in a pancreatic neuroendocrine tumor (pNET) model commonly used to study neoangiogenesis. The activation of the HIF-1α-24S-HC axis ultimately leads to the induction of the angiogenic switch through the positioning of proangiogenic neutrophils in proximity to Cyp46a1+ islets. Pharmacologic blockade or genetic inactivation of oxysterols controls pNET tumorigenesis by dampening the 24S-HC-neutrophil axis. Finally, we show that in some human pNET samples Cyp46a1 transcripts are overexpressed, which correlate with the HIF-1α target VEGF and with tumor diameter. This study reveals a layer in the angiogenic switch of pNETs and identifies a therapeutic target for pNET patients.