张华莉

教授 博士生导师 硕士生导师

入职时间:1997-07-09

所在单位:基础医学院

学历:博士研究生毕业

办公地点:湘雅老校区第二教学楼5楼

性别:女

联系方式:15607310187

学位:医学博士学位

在职信息:在职

主要任职:湖南省脓毒症转化医学重点实验室学术委员会副主任,湖南省病理生理学会副理事长,危重病专业委员会副主任委员,中国病理生理学会常务理事

毕业院校:中南大学

学科:基础医学

曾获荣誉:

2013-06-01  当选:  中南大学“升华学者”特聘教授

2013-06-01  当选:  湖南省自然科学杰出青年基金获得者

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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

点击次数:

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:

发表时间:2021-01-12

收录刊物:SCI

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