7,8-Dihydroneopterin
(Synonyms: 7,8-二氢-D-新蝶呤) 目录号 : GC45673An antioxidant
Cas No.:1218-98-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >85.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
7,8-Dihydroneopterin is a pteridine with antioxidant activities.[1] It scavenges 2,2-diphenyl-1-picrylhydrazyl radicals in a cell-free assay when used at concentrations ranging from 20 to 100 μM. 7,8-Dihydroneopterin (2-10 μM) inhibits copper ion-induced oxidation of LDL in a cell-free assay and decreases thiobarbituric acid reactive substances (TBARS) produced by THP-1 cells cultured with LDL.[2],[3] It inhibits necrosis induced by oxidized LDL (oxLDL) in U937, but not THP-1, cells when used at a concentration of 200 μM.[4]
Reference:
[1]. Oettl, K., Greilberger, J., and Reibnegger, G. Dihydroneopterin as a scavenger of nitrogen centered radicals. Pteridines 11(3), 90-93 (2000).
[2]. Gieseg, S.P., Reibnegger, G., Wachter, H., et al. 7,8 Dihydroneopterin inhibits low density lipoprotein oxidation in vitro. Evidence that this macrophage secreted pteridine is an anti-oxidant. Free Radic. Res. 23(2), 123-136 (1995).
[3]. Gieseg, S.P., and Cato, S. Inhibition of THP-1 cell-mediated low-density lipoprotein oxidation by the macrophage-synthesised pterin, 7,8-dihydroneopterin. Redox Rep. 8(2), 113-115 (2003).
[4]. Baird, S.K., Reid, L., Hampton, M.B., et al. OxLDL induced cell death is inhibited by the macrophage synthesised pterin, 7,8-dihydroneopterin, in U937 cells but not THP-1 cells. Biochim Biophys. Acta. 1745(3), 361-369 (2005).
| Cas No. | 1218-98-0 | SDF | |
| 别名 | 7,8-二氢-D-新蝶呤 | ||
| 化学名 | 2-amino-7,8-dihydro-6-[(1S,2R)-1,2,3-trihydroxypropyl]-4(3H)-pteridinone | ||
| Canonical SMILES | O=C1C2=C(NCC([C@H](O)[C@H](O)CO)=N2)NC(N)=N1 | ||
| 分子式 | C9H13N5O4 | 分子量 | 255.2 |
| 溶解度 | 0.3 mg/ml in DMF, 1 mg/ml in DMSO | 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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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.9185 mL | 19.5925 mL | 39.185 mL |
| 5 mM | 0.7837 mL | 3.9185 mL | 7.837 mL |
| 10 mM | 0.3918 mL | 1.9592 mL | 3.9185 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Neopterin/7,8-Dihydroneopterin is elevated in Duchenne muscular dystrophy patients and protects mdx skeletal muscle function
Exp Physiol 2018 Jul;103(7):995-1009.PMID:29791760DOI:10.1113/EP087031.
New findings: What is the central question of this study? We examined whether the macrophage-synthesized antioxidant 7,8-Dihydroneopterin was elevated in Duchenne muscular dystrophy (DMD) patients. We then examined whether 7,8-Dihydroneopterin could protect dystrophic skeletal mouse muscle from eccentric contraction-induced force loss and improve recovery. What is the main finding and its importance? Urinary neopterin/creatinine and 7,8-Dihydroneopterin/creatinine were elevated in DMD patients. 7,8-Dihydroneopterin attenuated eccentric contraction-induced force loss of dystrophic skeletal mouse muscle and accelerated recovery of force. These results suggest that eccentric contraction-induced force loss is mediated, in part, by an oxidative component and provides a potential protective role for 7,8-Dihydroneopterin in DMD. Abstract: Macrophage infiltration is a hallmark of dystrophin-deficient muscle. We tested the hypothesis that Duchenne muscular dystrophy (DMD) patients would have elevated levels of the macrophage-synthesized pterins, neopterin and 7,8-Dihydroneopterin, compared with unaffected age-matched control subjects. Urinary neopterin/creatinine and 7,8-Dihydroneopterin/creatinine were elevated in DMD patients, and 7,8-Dihydroneopterin/creatinine was associated with patient age and ambulation. Urinary 7,8-Dihydroneopterin corrected for specific gravity was also elevated in DMD patients. Given that 7,8-Dihydroneopterin is an antioxidant, we then identified a potential role for 7,8-Dihydroneopterin in disease pathology. We assessed whether 7,8-Dihydroneopterin could: (i) protect against isometric force loss in wild-type skeletal muscle exposed to various pro-oxidants; and (ii) protect wild-type and mdx muscle from eccentric contraction-induced force loss, which has an oxidative component. Force loss was elicited in isolated extensor digitorum longus (EDL) muscles by 10 eccentric contractions, and recovery of force after the contractions was measured in the presence of exogenous 7,8-Dihydroneopterin. 7,8-Dihydroneopterin attenuated isometric force loss by wild-type EDL muscles when challenged by H2 O2 and HOCl, but exacerbated force loss when challenged by SIN-1 (NO• , O2• , ONOO- ). 7,8-Dihydroneopterin attenuated eccentric contraction-induced force loss in mdx muscle. Isometric force production by EDL muscles of mdx mice also recovered to a greater degree after eccentric contractions in the presence of 7,8-Dihydroneopterin. The results corroborate macrophage activation in DMD patients, provide a potential protective role for 7,8-Dihydroneopterin in the susceptibility of dystrophic muscle to eccentric contractions and indicate that oxidative stress contributes to eccentric contraction-induced force loss in mdx skeletal muscle.
CD36 down regulation by the macrophage antioxidant 7,8-Dihydroneopterin through modulation of PPAR-γ activity
Free Radic Res 2022 May-Jun;56(5-6):366-377.PMID:36017639DOI:10.1080/10715762.2022.2114904.
CD36 is the key scavenger receptor driving the formation of cholesterol-loaded foam cells, the principal cellular component of atherosclerotic plaques. CD36 is down regulated by 7,8-Dihydroneopterin, a potent superoxide and hypochlorite scavenging antioxidant generated by interferon-γ stimulated macrophages. 7,8-Dihydroneopterin downregulates CD36 mRNA and protein levels so inhibiting macrophage foam cell formation in vitro. We examined the mechanism of 7,8-Dihydroneopterin downregulation of CD36 by measuring CD36 and PPAR-γ levels by Western blot analysis, in the monocyte-like U937 cells with a range of PPAR-γ stimulants and inhibitors. Lipoxygenase activity was measured by monitoring linoleic acid oxidation at 234 nm for diene formation. Between 100 and 200 μM, 7,8-Dihydroneopterin decreased CD36 levels by 50% within 12 h with levels dropping below 25% by 24 h. CD36 levels returned to basal levels after 24 h. Inhibition of protein synthesis by cycloheximide shows 7,8-Dihydroneopterin had no effect on CD36 degradation rates. PPAR-γ levels were not altered by the addition of 7,8-Dihydroneopterin. MAP Kinase, P38 and NF-κB pathways inhibitors SP600125, PD98059, SB202190 and BAY 11-7082, respectively, did not restore the CD36 levels in the presence of 7,8-Dihydroneopterin. The addition of the lipophilic PPAR-γ activators rosiglitazone and azelaoyl-PAF prevented the CD36 downregulation by 7,8-Dihydroneopterin. 7,8-Dihydroneopterin inhibited soybean lipoxygenase and reduced U937 cell basal levels of cellular lipid oxides as measured by HPLC-TBARS analysis. The data show 7,8-Dihydroneopterin down regulates CD36 expression by decreasing the level of lipid oxide stimulation of PPAR-γ promotor activity, potentially through lipoxygenase inhibition.
Potential to inhibit growth of atherosclerotic plaque development through modulation of macrophage neopterin/7,8-Dihydroneopterin synthesis
Br J Pharmacol 2008 Feb;153(4):627-35.PMID:17700723DOI:10.1038/sj.bjp.0707408.
The rise in plasma neopterin observed with increasing severity of vascular disease is a strong indicator of the inflammatory nature of atherosclerosis. Plasma neopterin originates as the oxidation product of 7,8-Dihydroneopterin secreted by gamma-interferon stimulated macrophages within atherosclerotic plaques. Neopterin is increasingly being used as a marker of inflammation during clinical management of patients with a range of disorders including atherosclerosis. Yet the role of 7,8-Dihydroneopterin/neopterin synthesis during the inflammatory process and plaque formation remains poorly understood and controversial. This is partially due to the unresolved role oxidants play in atherosclerosis and the opposing roles of 7,8-Dihydroneopterin/neopterin. Neopterin can act as pro-oxidant, enhancing oxidant damage and triggering apoptosis in a number of different cell types. Neopterin appears to have some cellular signalling properties as well as being able to chelate and enhance the reactivity of transition metal ions during Fenton reactions. In contrast, 7,8-Dihydroneopterin is also a radical scavenger, reacting with and neutralizing a range of reactive oxygen species including hypochlorite, nitric oxide and peroxyl radicals, thus protecting lipoproteins and various cell types including macrophages. This has led to the suggestion that 7,8-Dihydroneopterin is synthesized to protect macrophages from the oxidants released during inflammation. The oxidant/antioxidant activity observed in vitro appears to be determined both by the relative concentration of these compounds and the specific chemistry of the in vitro system under study. How these activities might influence or modulate the development of atherosclerotic plaque in vivo will be explored in this review.
Nucleoside transporters are critical to the uptake and antioxidant activity of 7,8-Dihydroneopterin in monocytic cells
Free Radic Res 2020 May;54(5):341-350.PMID:32375530DOI:10.1080/10715762.2020.1764948.
7,8-Dihydroneopterin protects cells intracellularly from oxidative stress-induced death, but its mode of transport across the cell membrane is unknown. Nucleosides, such as guanosine, are transported via nucleoside transporters of the equilibrative and concentrative forms. Therefore, the objective of this study was to identify which membrane transporters are responsible for 7,8-Dihydroneopterin transport in cells and whether this is necessary for protection against oxidative stress. Monocytic cell lines U937, THP-1 and human monocytes were incubated with varying concentrations of 7,8-Dihydroneopterin with or without nucleoside transporter inhibitors nitrobenzylthioinosine (NBMPR; ENT1), dipyridamole (DP; ENT1 and ENT2) or indomethacin (INDO; CNT). Only DP inhibited 7,8-Dihydroneopterin uptake in U937 cells, while NBMPR and DP inhibited 7,8-Dihydroneopterin uptake in THP-1 cells. All three inhibitors limited 7,8-Dihydroneopterin uptake in human monocytes at short time points only. When the cells were incubated with 10 mM of the peroxyl radical generator 2,2'-azobis-2-methyl-propanimidamide, dihydrochloride (AAPH) a 50-80% loss of cell viability was measured. 7,8-Dihydroneopterin protected all cell lines against AAPH-induced cell death, which was prevented with DP in U937 cells, NBMPR in THP-1 cells and a combination of all three nucleoside inhibitors in human monocytes. These data indicate 7,8-Dihydroneopterin is transported across the cell membrane of monocytic cells via equilibrative and concentrative nucleoside transporters in a cell lineage-dependent manner. The data also indicate protection from peroxyl radical-generated cell death with 7,8-Dihydroneopterin is intracellular and facilitated through nucleoside transporters in monocytic cells.
Effect of 7,8-Dihydroneopterin mediated CD36 down regulation and oxidant scavenging on oxidised low-density lipoprotein induced cell death in human macrophages
Int J Biochem Cell Biol 2017 Jun;87:27-33.PMID:28356230DOI:10.1016/j.biocel.2017.03.017.
The role of CD36 in oxidised low-density lipoprotein (oxLDL) mediated cell death was examined by down regulating the receptor level with the macrophage generated antioxidant 7,8-Dihydroneopterin. Down regulation of CD36 protein levels in human monocyte derived macrophages by 7,8-Dihydroneopterin corresponded to a decrease in CD36-mRNA. The oxidation products of 7,8-Dihydroneopterin, dihydroxanthopterin and neopterin did not significantly down regulate CD36. The CD36 down regulation resulted in a decrease in oxLDL uptake measured as 7-ketocholesterol accumulation. Though less oxLDL was taken up by the macrophages as a result of the 7,8-Dihydroneopterin induced down regulation in CD36 levels, the cytotoxicity of the oxLDL was not decreased. Addition of 7,8-Dihydroneopterin to oxLDL treated macrophages decreased the concentration of intracellular oxidants. In the presence of oxLDL, 7,8-Dihydroneopterin was oxidised to neopterin showing that the 7,8-Dihydroneopterin was scavenging intracellular oxidants generated in response to the oxLDL. The results show CD36 down regulation does not protect human macrophages form oxLDL cytotoxicity but 7,8-Dihydroneopterin intracellular oxidant scavenging is protective.