Asymmetric dimethylation and citrullination in the LEW.1AR1-iddm rat, an animal model of human type 1 diabetes, and effects of anti-TCR/anti-TNF-α antibody-based therapy
Asymmetric dimethylation and citrullination in the LEW.1AR1-iddm rat, an animal model of human type 1 diabetes, and effects of anti-TCR/anti-TNF-α antibody-based therapy
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DOI：
10.1007/s00726-019-02811-5
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发表时间：
2020-01-01
期刊：
影响因子：
3.5
通讯作者：
Joerns, Anne
中科院分区：
文献类型：
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作者：
Bollenbach, Alexander;Tsikas, Dimitrios;Joerns, Anne
LEW.1AR1-IDDM大鼠是人类1型糖尿病(T1D)的动物模型。用气相色谱-质谱法测定了正常血糖对照组(NGCO，n=6)、急性糖尿病(acT1D，n=6)、慢性糖尿病(chT1D，n=4)和治愈(cuT1D，n=4)大鼠器官蛋白中L精氨酸残基的不对称二甲基化程度(PrADMA)和瓜氨酸化程度(PrCit)。胰腺PrCit和PrADMA在两组间无差异，但存在相关性(r=0.728，P=0.0003，n=20)。AcT1D大鼠脾、肾组织中PrCit含量均低于NGCo大鼠。仅在脾组织中，cuT1D大鼠的PrADMA水平高于chT1D大鼠。联合治疗可在不改变胰腺PrADMA和PrCit的情况下，在脾内重建正常血糖和增加PrADMA。Western blotting显示不同的PrADMA模式，特别是在脾和胰腺中约为50 kDa的PrADMA，在胰腺中约为25 kDa的PrADMA，肾脏中仅显示非常微弱且很小的PrADMA。除了胰腺在不同代谢状态下的变化外，脾对识别T1D代谢变化的作用可能比迄今认为的更强。
The LEW.1AR1-iddm rat is an animal model of human type 1 diabetes (T1D). We determined by GC-MS the extent of asymmetric dimethylation (prADMA) and citrullination (prCit) of l-arginine residues in organ proteins (pr) of normoglycaemic control (ngCo, n = 6), acutely diabetic (acT1D, n = 6), chronically diabetic (chT1D, n = 4), and cured (cuT1D, n = 4) rats after anti-TCR/anti-TNF-alpha therapy. Pancreatic prCit and prADMA did not differ between the groups but were correlated (r = 0.728, P = 0.0003, n = 20). acT1D rats had lower prCit levels in spleen and kidney than ngCo rats. cuT1D rats had higher prADMA levels than chT1D rats only in the spleen. Combination therapy re-established normoglycaemia and increased prADMA in the spleen without altering pancreatic prADMA and prCit. Western blotting demonstrated the presence of different prADMA pattern, especially an approximate to 50-kDa prADMA in spleen and pancreas, and an approximate to 25-kDa prADMA in the pancreas only, with the kidney showing only a very faint and small prADMA. Besides the changes in the pancreas during different metabolic states, the spleen may play a stronger role for the recognition of metabolic changes in T1D than thought thus far.