Roles of AKAP1 in high-glucose induced mitochondrial fission in podocytes
10.3760/cma.j.issn.1001-7097.2018.07.008
- VernacularTitle:AKAP1在高糖诱导的足细胞线粒体分裂中的作用
- Author:
Yu TAO
1
;
Yiqiong MA
;
Zhaowei CHEN
;
Qian YANG
;
Guohua DING
Author Information
1. 430060,武汉大学人民医院肾内科
- Keywords:
Podocyte;
Mitochondrial;
Diabetic nephropathy;
A kinase anchoring protein 1;
Dynamin-related protein 1
- From:
Chinese Journal of Nephrology
2018;34(7):523-530
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the roles of A kinase anchoring protein1(AKAP1)in high-glucose induced mitochondrial fission in podocytes.Methods Conditionally immortalized human podocytes were cultured in serum-free medium for 24 hours,and then exposed to different glucose concentration conditions in different time periods.The protein expressions of AKAP1 were observed by immunofluorescence,and AKAP1,dynamin related protein1 (Drp1) and phospho Ser 637-Drp1 (p-Drp1)were analyzed by Western blotting.AKAP1 siRNA was transfected to block AKAP1 expression.Podocytes were then divided into normal control group (5 mmol/L glucose),hypertonic group (30 mmol/L mannitol+5 mmol/L glucose),high glucose group (35 mmol/L glucose),and high glucose+AKAP1 siRNA group.Mitochondrial morphological changes were assessed by mitotracker red staining.Podocyte apoptosis was assessed by flow cytometry.Results Compared with normal group,high-glucose induced more podocytes apoptosis (P ＜ 0.05),more mitochondrial fission with decreased aspect ratio and form factor (all P ＜ 0.05).Upregulated AKAP1 protein level,and increased ratio of p-Drp1/Drp1 (all P ＜ 0.05) in time and concentration dependent manners were also obscrvcd.Compared with high glucose group,transfection of AKAP1 siRNA showed less apoptosis (P ＜ 0.05),less mitochondrial fission with increased aspect ratio and form factor (all P ＜ 0.05),and down-regulated AKAP1 protein level as well as p-Drp1/Drp1 ratio (all P ＜ 0.05).Conclusion High glucose induced mitochondrial fission might be induced through AKAP1-Drp1 pathway.
