DMOG(dihydroxyalanine) is an antagonist of α-ketoglutarate cofactor and an inhibitor of HIF-proline hydroxylase, leading to the stability and accumulation of HIF-1α protein in the nucleus[4].
DMOG reduce susceptibility to endotoxemia by tolerating cells to LPS activation and promoting M2 polarization and subsequent up-regulation of IL-10 by peritoneal B1 cells[1]. DMOG inhibited hydroxyproline synthesis from chick embryo lung, with IC50 values of 9.3 μM and 3.7 μM corresponding to tissue and medium sources, respectively[2].The combination of DMOG and nSi exerted admirable effects on periodontal tissue regeneration. DMOG/nSi-PLGA fibrous membranes could enhance and orchestrate osteogenesis-angiogenesis[4].Inhibition of hydroxylase by oxygen sensing leads to upregulation of the transcription factors HIF-1α and NF-β under normal oxygen in vitro,0.1 to 1mM DMOG can stabilize the expression of HIF-1α[3].DMOG reduces FGF-2-induced proliferation and cyclin A expression by inhibiting prolyl hydroxylase activity in HPASMC[8]. DMOG acts as a pro-angiogenic agent and plays a protective role in experimental model of colitis and diarrhoea via HIF-1 related signal[5][6]. DMOG induces cell autophagy and protect cells from a subsequent OGD insult.[7].
DMOG inhibits endogenous HIF inactivation, and induces angiogenesis in ischaemic skeletal muscles of mice[5]. Up-regulation of hypoxia-inducible factor-1α by DMOG enhances the cardioprotective effects of ischemic postconditioning in hyperlipidemic rats[6].
参考文献:
[1]: Hams E, Saunders SP, et,al. The hydroxylase inhibitor dimethyloxallyl glycine attenuates endotoxic shock via alternative activation of macrophages and IL-10 production by B1 cells. Shock. 2011 Sep;36(3):295-302. doi: 10.1097/SHK.0b013e318225ad7e. PMID: 21844787; PMCID: PMC3157050.
[2]: Baader E, Tschank G, et,al. Inhibition of prolyl 4-hydroxylase by oxalyl amino acid derivatives in vitro, in isolated microsomes and in embryonic chicken tissues. Biochem J. 1994 Jun 1;300 ( Pt 2)(Pt 2):525-30. doi: 10.1042/bj3000525. PMID: 8002959; PMCID: PMC1138193.
[3]: Jaakkola P, Mole DR, et,al. Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science. 2001 Apr 20;292(5516):468-72. doi: 10.1126/science.1059796. Epub 2001 Apr 5. PMID: 11292861.
[4]: Shang L, Liu Z, Ma B, Shao J, Wang B, Ma C, Ge S. Dimethyloxallyl glycine/nanosilicates-loaded osteogenic/angiogenic difunctional fibrous structure for functional periodontal tissue regeneration. Bioact Mater. 2020 Oct 26;6(4):1175-1188. doi: 10.1016/j.bioactmat.2020.10.010. PMID: 33163699; PMCID: PMC7593348.
[5]: Milkiewicz M, Pugh CW, et,al. Inhibition of endogenous HIF inactivation induces angiogenesis in ischaemic skeletal muscles of mice. J Physiol. 2004 Oct 1;560(Pt 1):21-6. doi: 10.1113/jphysiol.2004.069757. Epub 2004 Aug 19. PMID: 15319416; PMCID: PMC1665195.
[6]: Li X, Zhao H, et,al. Up-regulation of hypoxia-inducible factor-1α enhanced the cardioprotective effects of ischemic postconditioning in hyperlipidemic rats. Acta Biochim Biophys Sin (Shanghai). 2014 Feb;46(2):112-8. doi: 10.1093/abbs/gmt132. Epub 2014 Jan 3. PMID: 24389644.
[7]: Singh A, Wilson JW, et,al. Hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors induce autophagy and have a protective effect in an in-vitro ischaemia model. Sci Rep. 2020 Jan 31;10(1):1597. doi: 10.1038/s41598-020-58482-w. Erratum in: Sci Rep. 2020 Apr 8;10(1):6041. PMID: 32005890; PMCID: PMC6994562.
[8]: Schultz K, Murthy V, et,al. Prolyl hydroxylase 2 deficiency limits proliferation of vascular smooth muscle cells by hypoxia-inducible factor-1{alpha}-dependent mechanisms. Am J Physiol Lung Cell Mol Physiol. 2009 Jun;296(6):L921-7. doi: 10.1152/ajplung.90393.2008. Epub 2009 Mar 20. PMID: 19304911; PMCID: PMC2692800.
DMOG（二羟基丙氨酸）是 α-酮戊二酸辅助因子的拮抗剂和 HIF-脯氨酸羟化酶的抑制剂，导致 HIF-1α 蛋白在细胞核中的稳定和积累[4]。< /p>\n
DMOG 通过使细胞耐受 LPS 激活并促进 M2 极化和随后腹膜 B1 细胞对 IL-10 的上调来降低对内毒素血症的易感性[1]。 DMOG抑制鸡胚肺中羟脯氨酸的合成，组织来源和培养基来源的IC50值分别为9.3 μM和3.7 μM[2]。DMOG和nSi联合使用对牙周组织再生具有良好的效果. DMOG/nSi-PLGA 纤维膜可增强和协调成骨-血管生成[4]。在体外常氧条件下，氧感应抑制羟化酶导致转录因子 HIF-1α 和 NF-β 上调,0.1 至 1mM DMOG 可以稳定 HIF-1α 的表达[3]。DMOG 通过抑制 HPASMC 中的脯氨酰羟化酶活性来降低 FGF-2 诱导的增殖和细胞周期蛋白 A 的表达[8]< /sup>。 DMOG 作为促血管生成剂，通过 HIF-1 相关信号在结肠炎和腹泻实验模型中发挥保护作用[5][6]。 DMOG 诱导细胞自噬并保护细胞免受随后的 OGD 损伤。[7]。
DMOG 抑制内源性 HIF 失活，并在小鼠缺血骨骼肌中诱导血管生成[5]。 DMOG上调缺氧诱导因子1α增强缺血后适应对高脂血症大鼠的心脏保护作用[6]。
| Cell experiment [1]: | |
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Cell lines |
B1 cells |
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Preparation Method |
B1 cells were FACS sorted from total peritoneal cells. Cells were cultured in the presence of DMOG (1 mM) for 2 h followed by stimulation. |
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Reaction Conditions |
1 mM DMOG for 2 hours |
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Applications |
The hydroxylase inhibitor DMOG reduce susceptibility to endotoxemia by tolerating cells to LPS activation and promoting M2 polarization and subsequent up-regulation of IL-10 by peritoneal B1 cells. |
| Animal experiment [2]: | |
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Animal models |
BALB/c and C57BL/6 mice |
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Preparation Method |
Intraperitoneal injection of DMOG |
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Dosage form |
8 mg DMOG / mouse |
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Applications |
DMOG significantly increased survival after LPS-induced shock. DMOG up-regulated the expression of IL-10 in peritoneal B-1 cells. Mice treated with DMOG before surgery developed severe worsening of disease symptoms and significantly increased mortality. |
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参考文献: [1]. Hams E, Saunders SP, et,al. The hydroxylase inhibitor dimethyloxallyl glycine attenuates endotoxic shock via alternative activation of macrophages and IL-10 production by B1 cells. Shock. 2011 Sep;36(3):295-302. doi: 10.1097/SHK.0b013e318225ad7e. PMID: 21844787; PMCID: PMC3157050. |
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