糖尿病患者血浆减少α-突触核蛋白的磷酸化和寡聚化

doi:10.3969/j.issn.1006-7795.2017.06.020

首都医科大学学报 ›› 2017, Vol. 38 ›› Issue (6): 879-883.doi: 10.3969/j.issn.1006-7795.2017.06.020

• Alpha-突触核蛋白的致病机制 • 上一篇下一篇

糖尿病患者血浆减少α-突触核蛋白的磷酸化和寡聚化

郑凇杨^1,2, 李昕^1,2,3,4, 杨巍巍^1,2,3,4, 李旭冉^1,2, 李旭颖^1,2, 于文娇^1,2, 于顺^1,2,3,4

1. 首都医科大学宣武医院神经生物学研究室, 北京市老年病医疗研究中心, 北京 100053;
2. 首都医科大学帕金森病临床诊疗与研究中心, 北京 100053;
3. 帕金森病北京市重点实验室和教育部神经变性病重点实验室, 北京 100053;
4. 国家老年疾病临床医学研究中心, 北京 100053

收稿日期:2017-10-23 出版日期:2017-11-21 发布日期:2017-12-16
通讯作者: 于顺 E-mail:yushun103@163.com
基金资助:
国家自然科学基金（81371200，81071014，81401042），北京市医院管理局"使命"计划专项经费资助（SML20150803）；北京市科学技术委员会资助（Z161100005116011，Z171100000117013）；北京市卫生和计划生育委员会"老年重大疾病关键技术研究"（PXM2017_026283_000002）。

Decreased α-synuclein phosphorylation and oligomerization in the plasma of patients with type 2 diabetes

Zheng Songyang^1,2, Li Xin^1,2,3,4, Yang Weiwei^1,2,3,4, Li Xuran^1,2, Li Xuying^1,2, Yu Wenjiao^1,2, Yu Shun^1,2,3,4

1. Department of Neurobiology, Xuanwu Hospital, Capital Medical University, Beijing Institute of Geriatrics, Beijing 100053, China;
2. Clinical Center for Parkinson's Disease, Capital Medical University, Beijing 100053, China;
3. Beijing Key Laboratory for Parkinson's Disease and Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing 100053, China;
4. National Clinical Research Center for Geriatric Disorders, Beijing 100053, China

Received:2017-10-23 Online:2017-11-21 Published:2017-12-16
Supported by:
This study was supported by National Natural Science Foundation of China (81371200, 81071014, 81401042); Beijing Municipal Administration of Hospitals' Mission Plan (SML20150803); Beijing Municipal Science & Technology Commission (Z161100005116011,Z171100000117013); Beijing Municipal commission of Health and Family Planning (PXM2017_026283_000002).

摘要/Abstract

摘要： 目的研究2型糖尿病（type 2 diabetes，T2D）患者血浆对α-突触核蛋白（α-synuclein，α-Syn）磷酸化和寡聚化聚集的影响。方法收集首都医科大学宣武医院内分泌科T2D住院患者70例，另收集年龄和性别与之匹配的健康志愿者70例作为对照组。采集抗凝血，并分离血浆。将基因重组人α-Syn在患者和对照志愿者血浆中振荡孵育，ELISA法检测各组人群血浆中寡聚化和磷酸化α-Syn形成量。结果 T2D患者血浆中寡聚化和磷酸化α-Syn形成量较对照组均有显著降低（P<0.05），且其与年龄有相关性。结论 T2D患者血浆以年龄依赖的方式减少寡聚化和磷酸化α-Syn的形成。

关键词: α-突触核蛋白, 2型糖尿病, 血浆, 磷酸化, 寡聚化

Abstract: Objective To investigate the effect of the plasma of patients with type 2 diabetes (T2D) patient on the formation of oligomeric and phosphorylated α-synuclein (α-Syn).Methods A total of 70 hospitalized patients with T2D and 70 age-and sex-matched healthy control subjects were recruited. Blood plasmas were collected and recombinant human α-Syn was incubated with the plasma. ELISA was used to measure the levels of oligomeric and phosphorylated α-syn formed in the plasma. Results The levels of oligomeric and phosphorylated α-syn in the plasma of T2D patients were significantly lower than those in the plasma of healthy controls (P<0.05), which was positively correlated with age.Conclusion Compared with control plasma, the plasma from T2D patients decreases α-syn oligomerization and phosphorylation in an age-dependent manner.

Key words: α-synuclein, type 2 diabetes, plasma, phosphorylation, oligomerization

中图分类号:

R338

郑凇杨, 李昕, 杨巍巍, 李旭冉, 李旭颖, 于文娇, 于顺. 糖尿病患者血浆减少α-突触核蛋白的磷酸化和寡聚化[J]. 首都医科大学学报, 2017, 38(6): 879-883.

Zheng Songyang, Li Xin, Yang Weiwei, Li Xuran, Li Xuying, Yu Wenjiao, Yu Shun. Decreased α-synuclein phosphorylation and oligomerization in the plasma of patients with type 2 diabetes[J]. Journal of Capital Medical University, 2017, 38(6): 879-883.

参考文献

[1] Kruger R, Kuhn W, Muller T,et al. Ala30Pro mutation in the gene encoding alpha-synuclein in parkinson's disease[J]. Nat Genet, 1998, 18(2):106-108.
[2] International Parkinson Disease Genomics Consortium, Nalls M A, Plagnol V, et al. Imputation of sequence variants for identification of genetic risks for Parkinson's disease:a meta-analysis of genome-wide association studies[J]. Lancet, 2011, 377(9766):641-649.
[3] Polymeropoulos M H, Lavedan C, Leroy E, et al.Mutation in the alpha-synuclein gene identified in families with Parkinson's disease[J]. Science, 1997, 276(5321):2045-2047.
[4] Rodriguez-Araujo G, Nakagami H, Takami Y, et al.Low alpha-synuclein levels in the blood are associated with insulin resistance[J]. Sci Rep, 2015, 5:12081.
[5] Shiuchi T, Haque M S, Okamoto S, et al. Hypothalamic orexin stimulates feeding-associated glucose utilization in skeletal muscle via sympathetic nervous system[J]. Cell Metab, 2009, 10(6):466-480.
[6] Ayala J E, Bracy D P, Malabanan C, et al. Hyperinsulinemic-euglycemic clamps in conscious, unrestrained mice[J]. J Vis Exp, 2011(57)pii:3188.
[7] Alberti K G, Zimmet P Z. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1:diagnosis and classification of diabetes mellitus provisional report of a WHO consultation[J]. Diabet Med, 1998,15(7):539-553.
[8] 陈予东, 尹娜, 李昕, 等. 脑卒中患者血浆中α-突触核蛋白及其寡聚体形成量变化的研究[J]. 首都医科大学学报, 2013, 34(6):826-829.
[9] Liu G, Chen M, Mi N, et al.Increased oligomerization and phosphorylation of α-synuclein are associated with decreased activity of glucocerebrosidase and protein phosphatase 2A in aging monkey brains[J]. Neurobiol Aging, 2015, 36(9):2649-2659.
[10] Galbo T, Olsen G S, Quistorff B, et al.Free fatty acid-induced PP2A hyperactivity selectively impairs hepatic insulin action on glucose metabolism[J]. PLoS One, 2011, 6(11):e27424.
[11] Højlund K, Poulsen M, Staehr P,et al. Effect of insulin on protein phosphatase 2A expression in muscle in type 2 diabetes[J]. Eur J Clin Invest, 2002, 32(12):918-923.
[12] Dillin A, Hsu A L, Arantes-Oliveira N, et al. Rates of behavior and aging specified by mitochondrial function during development[J]. Science, 2002, 298(5602):2398-2401.
[13] Lee S S, Lee R Y, Fraser A G, et al. A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity[J]. Nat Genet, 2003, 33(1):40-48.
[14] Short K R, Bigelow M L, Kahl J, et al. Decline in skeletal muscle mitochondrial function with aging in humans[J]. Proc Natl Acad Sci USA, 2005, 102(15):5618-5623.
[15] Riera C E, Dillin A. Tipping the metabolic scales towards increased longevity in mammals[J]. Nat Cell Biol, 2015, 17(3):196-203.
[16] Fujiwara H, Hasegawa M, Dohmae N,et al. alpha-Synuclein is phosphorylated in synucleinopathy lesions[J]. Nat Cell Biol, 2002, 4(2):160-164.
[17] Arawaka S, Wada M, Goto S,et al. The role of G-protein-coupled receptor kinase 5 in pathogenesis of sporadic Parkinson's disease[J]. J Neurosci, 2006, 26(36):9227-9238.
[18] Kragh C L, Lund L B, Febbraro F, et al. Alpha-synuclein aggregation and Ser-129 phosphorylation-dependent cell death in oligodendroglial cells[J]. J Biol Chem, 2009, 284:10211-10222.

糖尿病患者血浆减少α-突触核蛋白的磷酸化和寡聚化

Decreased α-synuclein phosphorylation and oligomerization in the plasma of patients with type 2 diabetes

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	苏志燕, 刘薇, 史婷婷. 老年2型糖尿病患者血尿酸浓度与代谢综合征的相关性分析[J]. 首都医科大学学报, 2023, 44(1): 137-142.
[2]	马艺欣, 张仲迎, 佀思聪, 罗鸿宇, 赵欢, 杨伟. 2型糖尿病患者新型脂肪因子血清内脏脂肪素和内脏脂肪特异性丝氨酸蛋白酶抑制因子的表达水平与左心室肥厚的关系[J]. 首都医科大学学报, 2022, 43(5): 767-773.
[3]	修双玲, 付俊玲, 穆志静, 孙丽娜, 赵蕾. 老年2型糖尿病患者体脂率对肌力和躯体功能的影响[J]. 首都医科大学学报, 2022, 43(4): 641-646.
[4]	宋丽敏, 李思源, 李军, 赵会荣, 李佳佳, 王双. 新疆石河子地区绝经后2型糖尿病女性SOST基因联合LRP5基因多态性及突变与骨代谢关系的研究[J]. 首都医科大学学报, 2022, 43(2): 269-274.
[5]	修双玲, 孙丽娜, 穆志静, 付俊玲, 赵蕾. 不同方法校正的肌肉质量与老年2型糖尿病躯体功能的相关性比较[J]. 首都医科大学学报, 2022, 43(2): 284-288.
[6]	杨柳青, 田红梅, 石汉平. 三种饮食模式与慢性疾病研究进展[J]. 首都医科大学学报, 2022, 43(2): 311-320.
[7]	刘立, 王冠, 赵鑫宇, 刘景院, 纪宇, 刘勇, 韩威, 翁以炳, 李昂. 双重滤过血浆置换治疗高脂血症胰腺炎的临床效果观察[J]. 首都医科大学学报, 2021, 42(6): 943-949.
[8]	高歌, 查旭, 刘伟进, 杨慧. 129位丝氨酸磷酸化α-突触核蛋白DELFIA检测方法的建立及初步应用[J]. 首都医科大学学报, 2021, 42(5): 776-782.
[9]	张冬雪, 文祯, 孙玉燕, 姜涛. 初诊2型糖尿病患者中肝脏胰岛素清除率与临床特点及胃肠激素相关性的初步分析[J]. 首都医科大学学报, 2021, 42(5): 822-828.
[10]	孔明, 李爽, 耿华, 周莉, 徐曼曼, 刘静, 陈煜. 双重血浆分子吸附系统治疗过程中肝素抗凝效果的影响因素研究[J]. 首都医科大学学报, 2021, 42(4): 647-652.
[11]	米颖馨, 王欣, 张开, 李可悦, 孙丽娜, 修双玲. 中老年男性2型糖尿病患者尿酸水平与肌少症的相关性研究[J]. 首都医科大学学报, 2021, 42(3): 453-458.
[12]	郑爽爽, 高志远, 宋双双, 何悦明, 卢洁. BOLD MRI评价糖尿病患者尿微量白蛋白及氧合水平的研究[J]. 首都医科大学学报, 2021, 42(1): 125-130.
[13]	王振中, 喻飞, 杨波, 马立峰. 富血小板血浆对兔骨关节炎软骨中基质金属蛋白酶-13表达的影响[J]. 首都医科大学学报, 2020, 41(6): 923-928.
[14]	李响, 蒲连美, 阮杨, 李红, 金泽宁. 汉族人群ADIPOR1 rs7539542与冠状动脉粥样硬化性心脏病和2型糖尿病的关联分析[J]. 首都医科大学学报, 2020, 41(6): 935-942.
[15]	尹星琪, 于彩果, 柯静, 赵冬, 于可. 2型糖尿病患者新型冠状病毒肺炎流行期间心理状态及行为调查[J]. 首都医科大学学报, 2020, 41(6): 970-977.