Dephosphorylation of AMP-activated protein kinase exacerbates ischemia/reperfusion-induced acute kidney injury via mitochondrial dysfunction
文献类型：期刊论文
| 作者 | Ma, Haijian1; Guo, Xiaozhen2; Cui, Shichao2; Wu, Yongmei3; Zhang, Yangming2,4 ; Shen, Xiaoyan1; Xie, Cen2; Li, Jingya2,5
|
| 刊名 | KIDNEY INTERNATIONAL
 |
| 出版日期 | 2022-02 |
| 卷号 | 101期号:2页码:315-330 |
| 关键词 | acute kidney injury AMPK autophagy lipid metabolism |
| ISSN号 | 0085-2538 |
| DOI | 10.1016/j.kint.2021.10.028 |
| 文献子类 | Article |
| 英文摘要 | Kidney tubular epithelial cells are high energy-consuming epithelial cells that depend mainly on fatty acid oxidation for an energy supply. AMP-activated protein kinase (AMPK) is a key regulator of energy production in most cells, but the function of AMPK in tubular epithelial cells in acute kidney disease is unclear. Here, we found a rapid decrease in Thr172-AMPKa phosphorylation after ischemia/reperfusion in both in vivo and in vitro models. Mice with kidney tubular epithelial cell-specific AMPKa deletion exhibited exacerbated kidney impairment and apoptosis of tubular epithelial cells after ischemia/reperfusion. AMPKa deficiency was accompanied by the accumulation of lipid droplets in the kidney tubules and the elevation of ceramides and free fatty acid levels following ischemia/reperfusion injury. Mechanistically, ischemia/reperfusion triggered ceramide production and activated protein phosphatase PP2A, which dephosphorylated Thr172-AMPKa. Decreased AMPK activity autophagy and impeded clearance of the dysfunctional mitochondria. Targeting the PP2A-AMPK axis by the dephosphorylation and promoting the mitophagy process. Thus, our study reveals that AMPKa plays an important role in protecting against tubular epithelial cell injury in for acute kidney injury treatment. |
| WOS关键词 | FATTY-ACID OXIDATION ; PHOSPHORYLATION ; HOMEOSTASIS ; METABOLISM ; MODEL ; GLUCOSE ; MUSCLE ; MICE ; AKI |
| WOS研究方向 | Urology & Nephrology |
| 语种 | 英语 |
| WOS记录号 | WOS:000746612100016 |
| 出版者 | ELSEVIER SCIENCE INC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309362]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Shen, Xiaoyan; Xie, Cen; Li, Jingya |
| 作者单位 | 1.Fudan Univ, Sch Pharm, Dept Pharmacol, 826 Zhang Heng Rd,Zhangjiang High Tech Pk, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 189 Guo Shou Jing Rd,501 Hai Ke Rd, Shanghai 201203, Peoples R China; 3.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Peoples R China; 4.Yantai Inst Mat Med, Yantai Key Lab Nanomed & Adv Preparat, Yantai, Shandong, Peoples R China; 5.Chinese Acad Sci, Sch Pharmaceut Sci & Technol, Hangzhou Inst Adv Study, Hangzhou, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ma, Haijian,Guo, Xiaozhen,Cui, Shichao,et al. Dephosphorylation of AMP-activated protein kinase exacerbates ischemia/reperfusion-induced acute kidney injury via mitochondrial dysfunction[J]. KIDNEY INTERNATIONAL,2022,101(2):315-330. |
| APA | Ma, Haijian.,Guo, Xiaozhen.,Cui, Shichao.,Wu, Yongmei.,Zhang, Yangming.,...&Li, Jingya.(2022).Dephosphorylation of AMP-activated protein kinase exacerbates ischemia/reperfusion-induced acute kidney injury via mitochondrial dysfunction.KIDNEY INTERNATIONAL,101(2),315-330. |
| MLA | Ma, Haijian,et al."Dephosphorylation of AMP-activated protein kinase exacerbates ischemia/reperfusion-induced acute kidney injury via mitochondrial dysfunction".KIDNEY INTERNATIONAL 101.2(2022):315-330. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。