Loss of AMPK exacerbates experimental autoimmune encephalomyelitis disease severity.
Loss of AMPK exacerbates experimental autoimmune encephalomyelitis disease severity.
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DOI：
10.1016/j.bbrc.2009.05.106
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发表时间：
2009-08-14
影响因子：
3.1
通讯作者：
Giri, Shailendra
中科院分区：
文献类型：
--
作者：
Nath, Narender;Khan, Musfiquidin;Rattan, Ramandeep;Mangalam, Ashutosh;Makkar, Randhir S.;de Meester, Carloe;Bertrand, Luc;Singh, Inderjit;Chen, Yingjie;Viollet, Benoit;Giri, Shailendra
AMP 激活蛋白激酶 (AMPK) 是哺乳动物细胞中的能量感应代谢开关。在此，我们报告了我们的新发现，即实验性自身免疫性脑脊髓炎 (EAE)（一种中枢神经系统 (CNS) 炎症性疾病）的所有免疫细胞中 AMPK 均丢失。 AMPKα1 主要在 T 细胞和抗原呈递细胞 (APC) 中表达，这些细胞主要参与 EAE 疾病的进展。与对照相比，从 EAE 患病动物分离的脾巨噬细胞、总 T 细胞及其亚群（CD4、CD8 和调节性 T 细胞）中，AMPK 在蛋白质水平上丢失，但不影响其 mRNA 水平，表明 AMPK 蛋白的丢失是转录后修饰的结果。为了检查其在炎症性疾病中的病理相关性，使用 MOG35-55 肽在野生型 (+/+) 和 AMPKα1 缺失小鼠 (−/−) 中诱导 EAE。与野生型小鼠相比，AMPKα1−/− 小鼠表现出严重的 EAE 疾病，伴有单核细胞的深度浸润，然而，AMPKα2 并不参与增强疾病的严重程度。从 AMPKα1−/− 免疫小鼠中分离的脾细胞显示出对 IFNγ 产生的显着诱导。我们的研究确定 AMPK 是所有免疫细胞疾病期间下调的靶点，恢复 AMPK 可能成为多发性硬化症 (MS) 等自身免疫性疾病的新治疗靶点。
AMP-activated protein kinase (AMPK) is an energy sensing metabolic switch in mammalian cells. Here, we report our novel finding that AMPK is lost in all immune cells of experimental autoimmune encephalomyelitis (EAE), an inflammatory disease of Central Nervous System (CNS). AMPKα1 is predominantly expressed in T cells and antigen presenting cells (APCs), which are primarily involved in EAE disease progression. AMPK is lost at protein level in spleen macrophages, total T cells and their subsets (CD4, CD8 and regulatory T cells) isolated from EAE afflicted animals compared to control, without affecting its mRNA levels suggesting that the loss of AMPK protein is the result of posttranscriptional modification. To examine its pathological relevance in inflammatory disease, EAE was induced in wild type (+/+) and AMPKα1 null mice (−/−) using MOG35–55 peptide. AMPKα1−/− mice exhibited severe EAE disease with profound infiltration of mononuclear cells compared to wild type mice however, AMPKα2 is not involved in enhancing the severity of the disease. Spleen cells isolated from AMPKα1−/− immunized mice exhibited a significant induction in the production of IFNγ. Our study identifies AMPK as a down regulated target during disease in all immune cells and possibly restoring AMPK may serve as a novel therapeutic target in autoimmune diseases like multiple sclerosis (MS).
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影响因子：
4.1
作者：
Al-Hakim, Abdallah K.;Zagorska, Anna;Alessi, Dario R.
通讯作者：
Alessi, Dario R.
影响因子：
4.8
作者：
Jorgensen, SB;Wojtaszewski, JFP;Pilegaard, H
通讯作者：
Pilegaard, H
影响因子：
168.9
作者：
Hartung, HP;Gonsette, R;Zwingers, T
通讯作者：
Zwingers, T
影响因子：
4.8
作者：
Momcilovic, Milica;Hong, Seung-Pyo;Carlson, Marian
通讯作者：
Carlson, Marian
影响因子：
4.7
作者：
Giri, Shailendra;Khan, Mushfiquddin;Singh, Avtar K.
通讯作者：
Singh, Avtar K.