SDMA (Symmetric dimethylarginine)
(Synonyms: 对称N,N-二甲基精氨酸,Symmetric dimethylarginine; NG,NG'-Dimethyl-L-arginine) 目录号 : GC33824
SDMA (Symmetric dimethylarginine)是精氨酸的甲基化形式，是一氧化氮合酶（NOS）的内源性抑制剂。
Cas No.:30344-00-4
Sample solution is provided at 25 µL, 10mM.
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SDMA (Symmetric dimethylarginine) is a methylated form of arginine and an endogenous inhibitor of nitric oxide synthase (NOS)[1]. SDMA inhibits vascular endothelial growth factor (VEGF)-induced endothelial nitric oxide synthase (eNOS) phosphorylation and nitric oxide production, but does not inhibit VEGFR2 activation and signaling leading to eNOS activation[2]. SDMA is a renal biomarker whose level is closely related to glomerular filtration rate and can diagnose renal disease earlier than traditional creatinine testing[3].
In vitro, SDMA (1.5, 3.1, 6.1μM) treatment of monocytes for 2h stimulated the expression of TNF-α and IL-6 in a concentration-dependent manner[4]. SDMA (100nM) treatment of glomerular endothelial cells for 30min abolished VEGF-induced nitric oxide synthesis and led to increased intracellular superoxide anion production[5].
In vivo, 28 days of SDMA infusion into healthy mice via osmotic minipumps (250µM/kg/day) resulted in a significant increase in SDMA levels, but had no effect on glomerular filtration rate, blood pressure, myocardial function, or renal histology[6].
References:
[1] Leiper J, Vallance P. Biological significance of endogenous methylarginines that inhibit nitric oxide synthases[J]. Cardiovascular research, 1999, 43(3): 542-548.
[2] Fiedler L R, Wojciak-Stothard B. The DDAH/ADMA pathway in the control of endothelial cell migration and angiogenesis[J]. Biochemical Society Transactions, 2009, 37(6): 1243-1247.
[3] Breit M, Weinberger K M. Metabolic biomarkers for chronic kidney disease[J]. Archives of biochemistry and biophysics, 2016, 589: 62-80.
[4] Schepers E, Barreto D V, Liabeuf S, et al. Symmetric dimethylarginine as a proinflammatory agent in chronic kidney disease[J]. Clinical Journal of the American Society of Nephrology, 2011, 6(10): 2374-2383.
[5] Feliers D, Lee D Y, Gorin Y, et al. Symmetric dimethylarginine alters endothelial nitric oxide activity in glomerular endothelial cells[J]. Cellular signalling, 2015, 27(1): 1-5.
[6] Veldink H, Faulhaber-Walter R, Park J K, et al. Effects of chronic SDMA infusion on glomerular filtration rate, blood pressure, myocardial function and renal histology in C57BL6/J mice[J]. Nephrology Dialysis Transplantation, 2013, 28(6): 1434-1439.
SDMA (Symmetric dimethylarginine)是精氨酸的甲基化形式，是一氧化氮合酶（NOS）的内源性抑制剂[1]。SDMA抑制血管内皮生长因子（VEGF）诱导的内皮一氧化氮合酶（eNOS）磷酸化和一氧化氮生成，但不能抑制VEGFR2激活和导致eNOS激活的信号传导[2]。SDMA 是一种肾脏生物标志物，其水平与肾小球滤过率密切相关，可以比传统的肌酐检测更早地诊断肾脏疾病[3]。
在体外，SDMA（1.5, 3.1, 6.1μM）处理单核细胞2h，浓度依赖性地刺激了TNF-α 和IL-6的表达[4]。SDMA（100nM）处理肾小球内皮细胞30min，消除了VEGF诱导的一氧化氮合成，并导致细胞内超氧阴离子产生增加[5]。
在体内，SDMA（250µM/kg/day）对健康小鼠通过渗透微型泵输注28天，导致SDMA水平显著增加，但对小鼠肾小球滤过率、血压、心肌功能和肾组织学没有影响[6]。
| Cell experiment [1]: | |
Cell lines | Monocytes |
Preparation Method | Whole blood was incubated with saline (control) or different doses of ADMA (0.6, 3.6, and 36μM) or SDMA (1.5, 3.1, and 6.1μM) for 2h in a humidified atmosphere of 5% CO2 in air at 37°C. Cells were finally stained for intracellular TNF-α or IL-6. Samples were analyzed with a flow cytometer. |
Reaction Conditions | 1.5, 3.1, 6.1μM; 2h |
Applications | SDMA has a proinflammatory effect on monocytes, stimulated the expression of TNF-α and IL-6，which could not be demonstrated for its structural analog ADMA. |
| Animal experiment [2]: | |
Animal models | C57Bl/6 mice |
Preparation Method | Mice received vehicle-controlled infusion of SDMA (250µM/kg/day) for 28 days using osmotic minipumps (n=24/group). The following parameters were monitored: glomerular filtration rate, cardiac function and blood pressure. Blood samples for SDMA determination were obtained at baseline, 2 and 4 weeks. Mice were euthanized at 4 weeks to obtain tissue for renal histology. |
Dosage form | 250µM/kg/day, 28 days; Osmotic minipump infusion |
Applications | Chronic SDMA infusion led to a significant increase of SDMA levels from 0.26±0.10 to 3.49±1.66µM at 4 weeks. Chronic SDMA infusion has no effect on glomerular filtration rate, blood pressure, myocardial function, and renal histology in mice. |
References: [1]Schepers E, Barreto D V, Liabeuf S, et al. Symmetric dimethylarginine as a proinflammatory agent in chronic kidney disease[J]. Clinical Journal of the American Society of Nephrology, 2011, 6(10): 2374-2383. [2]Veldink H, Faulhaber-Walter R, Park J K, et al. Effects of chronic SDMA infusion on glomerular filtration rate, blood pressure, myocardial function and renal histology in C57BL6/J mice[J]. Nephrology Dialysis Transplantation, 2013, 28(6): 1434-1439. | |
| Cas No. | 30344-00-4 | SDF | |
| 别名 | 对称N,N-二甲基精氨酸,Symmetric dimethylarginine; NG,NG'-Dimethyl-L-arginine | ||
| Canonical SMILES | N[C@@H](CCCN/C(NC)=N/C)C(O)=O | ||
| 分子式 | C8H18N4O2 | 分子量 | 202.25 |
| 溶解度 | DMSO : 50 mg/mL (247.22 mM; ultrasonic and adjust pH to 3 with 1M HCl) | 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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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 4.9444 mL | 24.7219 mL | 49.4438 mL |
| 5 mM | 0.9889 mL | 4.9444 mL | 9.8888 mL |
| 10 mM | 0.4944 mL | 2.4722 mL | 4.9444 mL |
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| 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 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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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，
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2.
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