Inhibition of aerobic glycolysis alleviates sepsis-induced acute kidney injury by promoting lactate/Sirtuin 3/AMPK-regulated autophagy
发布时间：2021-06-02
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影响因子：3.098
发表刊物：Int J Mol Med .
关键字：aerobic glycolysis, 2-deoxy-D-glucose, autophagy, acute kidney injury, sepsis
摘要：Metabolism reprogramming influences the severity of organ dysfunction, progression to fibrosis, and development of disease in acute kidney injury (AKI). Previously we showed that inhibition of aerobic glycolysis improved survival rates and protected septic mice from kidney injury. However, the underlying mechanisms remain unclear. In the present study, it was revealed that sepsis or lipopolysaccharide (LPS) enhanced aerobic glycolysis as evidenced by increased lactate production and upregulated mRNA expression of glycolysis-related genes in kidney tissues and human renal tubular epithelial (HK-2) cells. The aerobic glycolysis inhibitor 2-deoxy-D-glucose (2-DG) downregulated glycolysis, and improved kidney injury induced by sepsis. 2-DG treatments increased the expression of sirtuin 3 (SIRT3) and phosphorylation-AMP-activated protein kinase (p-AMPK), following promoted autophagy and attenuated apoptosis of tubular epithelial cells in septic mice and in LPS-treated HK-2 cells. However, the glycolysis metabolite lactate downregulated SIRT3 and p-AMPK expression, inhibited autophagy and enhanced apoptosis in LPS-treated HK-2 cells. Furthermore, pharmacological blockade of autophagy with 3-methyladenine (3-MA) partially abolished the protective effect of 2-DG in sepsis-induced AKI. These findings indicated that inhibition of aerobic glycolysis protected against sepsis-induced AKI by promoting autophagy via the lactate/SIRT3/AMPK pathway.
合写作者：Tao Li,Huan Chen,Ke Liu,Meidong Liu
第一作者：Chuyi Tan,Jia Gu
论文类型：基础研究
通讯作者：Huali Zhang(通讯作者),Xianzhong Xiao
学科门类：医学
一级学科：基础医学
期号：2021 Mar;47(3):19.？doi: 10.3892/ijmm.2021.4852.
是否译文：否
发表时间：2021-01-12
收录刊物：SCI