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]。