单羧酸转运蛋白1在低糖条件下促进M1型小胶质细胞中诱导型一氧化氮合酶表达

doi:10.16098/j.issn.0529-1356.2022.03.003

解剖学报 ›› 2022, Vol. 53 ›› Issue (3): 288-294.doi: 10.16098/j.issn.0529-1356.2022.03.003

单羧酸转运蛋白1在低糖条件下促进M1型小胶质细胞中诱导型一氧化氮合酶表达

于哲成¹ 张晓艳² 杜娟娟¹ 周鹏^1*

1.温州医科大学神经研究所，浙江温州325035; 2.温州医科大学附属第二医院中医系，浙江温州 325035

收稿日期:2021-10-14 修回日期:2021-12-07 出版日期:2022-06-06 发布日期:2019-06-06
通讯作者: 周鹏 E-mail:zxnp8888@163.com
基金资助:
浙江省自然基金

Monocarboxylate transporter 1 enhancing the expression of inducible nitric oxide synthase within M1 phenotype microglia under low-glucose condition

YU Zhe-cheng¹ ZHANG Xiao-yan² DU Juan-juan¹ ZHOU Peng^1*

1.Institute of Neuroscience, Basic Medical College of Wenzhou Medical University, Zhejiang Wenzhou 325035, China; 2.Department of Chinese Traditional Medicine, the Second Affiliated Hospital of Wenzhou Medical University, Zhejiang Wenzhou 325035, China

Received:2021-10-14 Revised:2021-12-07 Online:2022-06-06 Published:2019-06-06
Contact: ZHOU Peng E-mail:zxnp8888@163.com
Supported by:
Natural Science of the Zhejiang Province Foundation

摘要/Abstract

摘要：

目的探讨在缺血环境下诱导型一氧化氮合酶(iNOS)和单羧酸转运蛋白1(MCT1)与M1型促炎性小胶质细胞的关系。方法小鼠6只，采用光化学栓塞法制作脑缺血模型；BV2细胞使用含5mmol/L低糖培养基刺激2h。使用免疫荧光染色、Western blotting方法检测缺血小鼠大脑中小胶质细胞和低糖刺激的BV2细胞中iNOS、MCT1及精氨酸酶1(ARG1)的表达。用RNA干扰及质粒转染技术分别调控未处理BV2细胞中的MCT1表达，检测iNOS及ARG1的变化。结果激光制作脑缺血模型成功后，缺血侧半球中iNOS和MCT1以及ARG1的表达升高（P<0.01），且MCT1主要表达在离子钙接头蛋白分子1（Iba1）阳性和iNOS阳性的小胶质细胞中。低糖刺激BV2小胶质细胞后，iNOS和MCT1表达升高（P<0.001），而ARG1表达降低（P<0.01），MCT1主要表达在iNOS阳性的BV2细胞中。RNA干扰BV2细胞后，细胞中MCT1表达降低，iNOS表达下降（P<0.01）；质粒转染BV2细胞后，MCT1表达增高，iNOS表达增加（P<0.01）。但在两种情况下，ARG1表达水平均未发生明显变化。结论在低糖环境中小胶质细胞向M1表型极化，MCT1和iNOS表达同时增高，MCT1参与iNOS的表达上调，可能处于iNOS调节通路的上游。

关键词: 诱导型一氧化氮合酶, 单羧酸转运蛋白1, 缺血性脑卒中, 小胶质细胞, 光化学栓塞法, 免疫印迹法, 小鼠

Abstract:

Objective To testify the link between the increase of inducible nitric oxide synthase (iNOS) and monocarboxylate transporter 1 (MCT1) expression in the M1 phenotype microglia under ischemic condition. Methods Photothrombosic ischemia stroke model was applied in 6 mice. BV2 cells were treated with low glucose medium contained 5mmol/L glucose for 2 hours. Immunofluorescent staining and Western blotting were used to check the responses from microglia in the mouse brains subjected to ischemia and BV2 cells were treated with low-glucose treatment. Application of RNA interference or plasmid transfection were used to regulate the MCT1 expression in BV2 cells. Results The expression levels of iNOS, MCT1 and arginase-1 (ARG1) increased in the ischemic side compared to the non-ischemic side of mice brain(P<0.01). In the BV2 cells exposed to low-glucose condition, iNOS and MCT1 levels increased(P<0.001), whereas ARG1 level decreased(P<0.01). RNA interference interfered the expression of MCT1 and then decreased the iNOS expression(P<0.01), while overexpression of MCT1 through plasmid transfection increased iNOS expression(P<0.01), while the ARG1 expressions in both conditions were not changed significantly. Conclusion After microglia polarized into inflammatory phenotype during ischemia period, iNOS production is related with MCT1 expression, and MCT1 is in the upstream of iNOS pathway.

Key words: Inducible nitric oxide synthase, Monocarboxylate transporter 1, Ischemic stroke, Microglia, Photochemical embolization, Western blotting, Mouse

中图分类号:

Q189

于哲成张晓艳杜娟娟周鹏 . 单羧酸转运蛋白1在低糖条件下促进M1型小胶质细胞中诱导型一氧化氮合酶表达[J]. 解剖学报, 2022, 53(3): 288-294.

YU Zhe-cheng ZHANG Xiao-yan DU Juan-juan ZHOU Peng. Monocarboxylate transporter 1 enhancing the expression of inducible nitric oxide synthase within M1 phenotype microglia under low-glucose condition [J]. Acta Anatomica Sinica, 2022, 53(3): 288-294.

参考文献

［1］Wolf SA, Boddeke HW, Kettenmann H. Microglia in Physiology and Disease［J］. Annu Rev Physiol, 2017, 79:619-643.

［2］Collmann FM, Pijnenburg R,Hamzei-Taj S,et al. Individual in vivo profiles of microglia polarization after stroke, represented by the genes iNOS and Ym1［J］. Front Immunol,2019,10:1236.

［3］Liddelow SA,Guttenplan KA,ClarkeK LE,et al. Neurotoxic reactive astrocytes are induced by activated microglia［J］. Nature,2017,541(7638): 481-487.

［4］Tang Y, Le W. Differential roles of M1 and M2 microglia in neurodegenerative diseases［J］. Mol Neurobiol,2015, 53(2):1181-1194.

［5］Yeh FL, Hansen DV, Sheng M. TREM2, microglia, and neurodegenerative diseases［J］. Trends Mol Med,2017,23(6): 512-533.

［6］Kierdorf K, Prinz M. Microglia: same same, but different［J］. J Exp Med, 2019,2169(10): 2223-2225.

［7］Colonna M,Butovsky O. Microglia function in the central nervous system during health and neurodegeneration［J］. Annu Rev Immunol,2017,35:441-468.

［8］Zhao B, Wang H, Li CX, et al. GPR17 mediates ischemia-like neuronal injury via microglial activation［J］. Int J Mol Med,2018, 42(5): 2750-2762.

［9］Shen Y, Kapfhamer D, Minnella AM, et al. Bioenergetic state regulates innate inflammatory responses through the transcriptional co-repressor CtBP［J］. Nat Commun,2017,8(1): 624.

［10］Ghosh S, Castillo E, Frias ES, et al. Bioenergetic regulation of microglia［J］. Glia,2017, 66(6):1200-1212.

［11］Galván-Pe?a S, O’Neill LA. Metabolic reprograming in macrophage polarization［J］. Front Immunol,2014, 5:420.

［12］Salter MW, Stevens B. Microglia emerge as central players in brain disease［J］. Nat Med,2017, 23(9): 1018-1027.

［13］Hashimoto T, Hussien R,Cho HS, et al. Evidence for the mitochondrial lactate oxidation complex in rat neurons: demonstration of an essential component of brain lactate shuttles［J］. PLoS One, 2008,3(8): e2915.

［14］Moreira TJ, Maekawa F, Repond C,et al. Enhanced cerebral expression of MCT1 and MCT2 in a rat ischemia model occurs in activated microglial cells［J］, J Cereb Blood Flow Metab,2009, 29(7): 1273-1283.

［15］Kong L, Wang Z, Liang X, et al. Monocarboxylate transporter 1 promotes classical microglial activation and proinflammatory effect via 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase3［J］. J Neuroinflammation, 2019,16(1):240.

［16］Zhao Z,Wu MS, Zou C,et al. Downregulation of MCT1 inhibits tumor growth, metastasis and enhances chemotherapeutic efficacy in osteosarcoma through regulation of the NF-κB pathway［J］.Cancer Letters,2014,342(1)150-158.

［17］Huang C,Lu X, Wang JL, et al. Compound C induces the ramification of murine microglia in an AMPK-independent and small rhogtpase-dependent manner［J］. Neuroscience,2016, 331:24-39.

［18］Subedi L, Lee JH, Yumnam S, et al. Anti-inflammatory effect of sulforaphane on LPS-activated microglia potentially through JNK/AP-1/NF-kB inhibition and Nrf2/HO-1 activation［J］. Cells,2019,8(2):194.

［19］Yang L, Renyuan Zhoua, Yu Tong,et al. Neuroprotection by dihydrotestosterone in LPS-induced neuroinflammation［J］. Neurobiol Dis，2020，140：104814.

［20］Du JJ，Ye Zh，Zhou T，et al. Small ubiquitin-like modifier proteins specific protease 3 in microgliaparticipating in the early progression of photothrombosic ischemic stroke mice model［J］. Acta Anatomica Sinica,2021,52(4):548-553.(in Chinese)

杜娟娟，叶蓁，周涛，等.小胶质细胞中小泛素样修饰蛋白特异性蛋白酶3参与小鼠光化学栓塞法缺血性脑卒中早期的疾病进展［J］.解剖学报,2021，52(4)：548-553.

［21］Sickmann HM, Walla AB, Schousboe A, et al. Functional significance of brain glycogen in sustaining glutamatergic neurotransmission［J］. J Neurochem,2009, 109（Suppl 1）: 80-86.

［22］Zhou P,Guan T, Jiang Z,et al. Monocarboxylate transporter 1 and the vulnerability of oligodendrocyte lineage cells to metabolic stresses［J］. CNS Neurosci Ther,2018, 24(2):126-134.

［23］Pereira-Vieira J, Preto A, Casal M, et al. MCT1, MCT4 and CD147 expression and 3-bromopyruvate toxicity in colorectal cancer cells are modulated by the extracellular conditions［J］. Biol Chem,2019,400(6):787-799.

［24］Yue Y,Stone S,Lin W. Role of nuclear factor kappaB in multiple sclerosis and experimental autoimmune encephalomyelitis［J］. Neural Regen Res,2018,13(9):1507-1515.

[1]	洪晓敏李三强崔钦奕郑润月杨孟利罗仁利李前辉 . 酒精性肝纤维化核因子κB信号通路与性别的差异 [J]. 解剖学报, 2024, 55(1): 55-61.
[2]	魏茜茜李超红赵晨露唐家萍刘玉珍. 大鼠颈上神经节中Ⅰ组代谢型谷氨酸受体表达及慢性间歇性低氧对其的影响 [J]. 解剖学报, 2024, 55(1): 3-9.
[3]	袁蕾杨智伟杨惠刘政海何洁万炜. 三七总皂苷抑制小鼠星形胶质细胞活化缓解完全弗氏佐剂所致炎性痛 [J]. 解剖学报, 2024, 55(1): 25-31.
[4]	马婷婷陈建红刘爱翠李海宁. 抑制lncRNA TUG1下调核苷酸结合寡聚结构域样受体蛋白1炎症小体在延缓阿尔茨海默病进展的作用 [J]. 解剖学报, 2024, 55(1): 32-42.
[5]	邹成功冯浩陈兵唐辉邵川孙谋杨荣何家全. 创伤性颅脑损伤中神经功能障碍与认知功能损伤的动态变化 [J]. 解剖学报, 2024, 55(1): 43-48.
[6]	吕海燕沈西雅赵富生朱梅. 松茸多糖对 1-甲基-4-苯基-吡啶离子诱导 PC12 细胞损伤的影响 [J]. 解剖学报, 2024, 55(1): 49-54.
[7]	郑丽平刘霞杜晓华吴亚娟刘珊珊 . 脑源性神经营养因子在牦牛与黄牛端脑不同区域的表达与分布 [J]. 解剖学报, 2024, 55(1): 10-16.
[8]	郝永明郭磊周程辉裴汉军李莉赵哲 . 改良腹主动脉缩窄法建立心肌肥厚模型[J]. 解剖学报, 2024, 55(1): 120-124.
[9]	许亚平余悦欣陈金福王柯柯郭志坤 . 高龄大鼠心室肌间质弹性纤维和胶原纤维的结构分布特征及其机制 [J]. 解剖学报, 2023, 54(6): 716-721.
[10]	王文娟丁雨桐苏昊任捷孙艳荣王涵菲陆嘉莉张林倩白钰秦丽华. 低雌激素状态下大鼠海马及纹状体Nogo-A的表达变化[J]. 解剖学报, 2023, 54(6): 620-627.
[11]	张琴杨俊霞蒋青松. 福辛普利对糖尿病视网膜病变小鼠血管紧张素转化酶2和血管内皮生长因子的影响[J]. 解剖学报, 2023, 54(6): 628-634.
[12]	陈子璇司丽娜舒薇菡张欣魏晨阳程露阳杨松鹤乔跃兵. 褪黑素调控下丘脑PI3K/Akt/mTOR信号延缓雌性小鼠青春期启动的机制 [J]. 解剖学报, 2023, 54(6): 644-651.
[13]	梁盼盼禹爱梅杜静寇文辉王欢欢宋爱霞. 基于c-Jun氨基末端激酶/p38丝裂原活化蛋白激酶信号通路探讨阿魏酸钠对偏头痛大鼠炎症反应的抑制作用[J]. 解剖学报, 2023, 54(6): 652-659.
[14]	徐颖刘斌郑兴何宗钊. 补体C3a受体在盲肠结扎穿孔致脓毒症大鼠认知障碍中的作用及机制 [J]. 解剖学报, 2023, 54(6): 668-675.
[15]	刘哲川李坤马帅男孟家琪王艳芹. 利拉鲁肽对百草枯诱导的小鼠帕金森病模型炎症及线粒体融合/分裂的影响 [J]. 解剖学报, 2023, 54(6): 676-681.

单羧酸转运蛋白1在低糖条件下促进M1型小胶质细胞中诱导型一氧化氮合酶表达

Monocarboxylate transporter 1 enhancing the expression of inducible nitric oxide synthase within M1 phenotype microglia under low-glucose condition

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