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L-α-Hydroxyglutaric Acid
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
L-α-Hydroxyglutaric Acid图片
包装与价格:
包装价格(元)
1mg电议
5mg电议
10mg电议
25mg电议

产品介绍
L-α-Hydroxyglutaric Acid 是一种表观遗传修饰剂和推定的肾癌代谢物。 L-α-Hydroxyglutaric Acid 可以抑制组蛋白去甲基化酶,从而促进组蛋白甲基化。 L-α-Hydroxyglutaric Acid 抑制线粒体肌酸激酶 (Mi-CK) 活性,Km 和 Ki 分别为 2.52 mM 和 11.13 mM。

Cell lines

CD8-positive T-lymphocytes

Preparation Method

Cells were activated with anti-CD3 and anti-CD28 antibodies for 48 h, then expanded for an additional 4 days in the presence of IL-2 and then treated with the indicated concentration of L-α-Hydroxyglutaric Acid for 16 h.

Reaction Conditions

300,500 μM L-α-Hydroxyglutaric Acid for 16 h

Applications

L-α-Hydroxyglutaric Acid inhibited the production of effector cytokines and reduced cytotoxicity. In addition, when the dose of L-α-Hydroxyglutaric Acid was more than 300 μM, L-α-Hydroxyglutaric Acid inhibited cell expansion, increased cell apoptosis, decreased IFN-γ secretion, but increased IL-2 secretion.

Animal models

Wistar rats

Preparation Method

The homogenates of different mouse tissues were mixed with the corresponding buffer, and L-α-Hydroxyglutaric Acid at a final concentration of 0.25 to 5 mM was also added to the medium.

Dosage form

0.25 to 5 mM L-α-Hydroxyglutaric Acid for 15 min at 37 ℃

Applications

When examined the effect of L-α-Hydroxyglutaric Acid, at concentrations varying from 1 to 5 mM, on CK activity in total homogenates from cerebellum, cerebral cortex, skeletal muscle and cardiac muscle. L-α-Hydroxyglutaric Acid did not alter tCK activities from cerebral cortex, skeletal muscle, and cardiac muscle, but significantly inhibited the enzyme activity from cerebellum at all concentrations tested.

产品描述

L-α-Hydroxyglutaric Acid is an important metabolite in various domains of life. In mammals and plants, it is produced by lactate dehydrogenase (LDH) and malate dehydrogenase (MDH)-mediated 2-ketoglutarate (2-KG) reduction under hypoxic conditions[2]. L-α-Hydroxyglutaric Acid is an inhibitor of 2-KG dependent dioxygenases with specific pro-oncogenic capabilities[3,4].

In CD8-positive T-lymphocytes, L-α-Hydroxyglutaric Acid inhibited the production of effector cytokines and reduced cytotoxicity. In addition, when the dose of L-α-Hydroxyglutaric Acid was more than 300 μM, L-α-Hydroxyglutaric Acid inhibited cell expansion, increased cell apoptosis, decreased IFN-γ secretion, but increased IL-2 secretion[6].This compound was identified to aid the proliferation and antitumorigenic abilities of CD8+ T-lymphocytes, to contribute to relieving the cellular reductive stress[5].

When examined the effect of L-α-Hydroxyglutaric Acid, at concentrations varying from 1 to 5 mM, on CK activity in total homogenates from cerebellum, cerebral cortex, skeletal muscle and cardiac muscle. L-α-Hydroxyglutaric Acid did not alter tCK activities from cerebral cortex, skeletal muscle, and cardiac muscle, but significantly inhibited the enzyme activity from cerebellum at all concentrations tested. The inhibition of Mi-CK activity by L-α-Hydroxyglutaric Acid is non-competitive. The Km calculated was 2.52±0.74 mM. The Ki value was calculated by the method of which provides a simple way of determining the inhibition constant (Ki) for non-competitive inhibitors. The Ki value calculated was 11.13±3.71 mM for L-α-Hydroxyglutaric Acid[1].

Besides, in Zebrafish, L-α-Hydroxyglutaric Acid-induced apoptosis was caused by oxidation[7].

References:
[1]: da Silva CG, Bueno AR, et,al. L-2-hydroxyglutaric acid inhibits mitochondrial creatine kinase activity from cerebellum of developing rats. Int J Dev Neurosci. 2003 Jun;21(4):217-24. doi: 10.1016/s0736-5748(03)00035-2. PMID: 12781789.
[2]: Oldham WM, Clish CB, et,al. Hypoxia-Mediated Increases in L-2-hydroxyglutarate Coordinate the Metabolic Response to Reductive Stress. Cell Metab. 2015 Aug 4;22(2):291-303. doi: 10.1016/j.cmet.2015.06.021. Epub 2015 Jul 23. PMID: 26212716; PMCID: PMC4526408.
[3]: Xu W, Yang H, et,al. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Cancer Cell. 2011 Jan 18;19(1):17-30. doi: 10.1016/j.ccr.2010.12.014. PMID: 21251613; PMCID: PMC3229304.
[4]: Chowdhury R, Yeoh KK, et,al. The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases. EMBO Rep. 2011 May;12(5):463-9. doi: 10.1038/embor.2011.43. Epub 2011 Apr 1. PMID: 21460794; PMCID: PMC3090014.
[5]: Tyrakis PA, Palazon A, et,al. S-2-hydroxyglutarate regulates CD8+ T-lymphocyte fate. Nature. 2016 Dec 8;540(7632):236-241. doi: 10.1038/nature20165. Epub 2016 Oct 26. PMID: 27798602; PMCID: PMC5149074.
[6]: Tyrakis PA, Palazon A, et,al. S-2-hydroxyglutarate regulates CD8+ T-lymphocyte fate. Nature. 2016 Dec 8;540(7632):236-241. doi: 10.1038/nature20165. Epub 2016 Oct 26. PMID: 27798602; PMCID: PMC5149074.
[7]:Parng C, Ton C, et,al. A zebrafish assay for identifying neuroprotectants in vivo. Neurotoxicol Teratol. 2006 Jul-Aug;28(4):509-16. doi: 10.1016/j.ntt.2006.04.003. Epub 2006 Jun 30. PMID: 16814516.