Aspirin intervenes in hyperlipidemia kidney damage by blocking endoplasmic reticulum stress in podocytes
10.3760/cma.j.issn.1001-7097.2020.02.011
- VernacularTitle: 阿司匹林阻断高脂血症诱导的足细胞内质网应激的机制
- Author:
Yudong CHU
1
;
Rongshan LI
2
;
Yuan TIAN
2
;
Pengjie XU
1
;
Jiang LIU
1
;
Xiaohui QIU
1
;
Shizhong BU
3
Author Information
1. Department of Nephrology, Ningbo Medical Center Lihuili Hospital, Ningbo 315000, China
2. Department of Nephrology, Shanxi Provincial People's Hospital, Taiyuan 030000, China
3. Diabetes Research Center, Ningbo University, Ningbo 315000, China
- Publication Type:Journal Article
- Keywords:
Aspirin;
Hyperlipidemias;
Lipoproteins, LDL;
Podocytes;
Endoplasmic reticulum stress
- From:
Chinese Journal of Nephrology
2020;36(2):139-144
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effects and underlying mechanisms of aspirin on endoplasmic reticulum stress in podocytes induced by hyperlipemia.
Methods:Cultured podocytes were divided into four groups: control group, aspirin (100 μg/ml) group, oxidized low density lipoprotein (ox-LDL, 100 μg/ml) group, aspirin+ox-LDL group. The expression of protein kinase R-1ike endoplasmic reticulum kinase (PERK), eukaryotic translation initiation factor 2α (eIF2α), activating transcription factor-4 (ATF4) and CAAT/enhancer binding protein homologous protein (CHOP) at 6 h, 12 h, 24 h, 48 h were evaluated by real-time PCR. The related proteins of p-PERK and p-eIF2α at 24 h and ATF4 at 12 h were evaluated by Western blotting, respectively.
Results:The expressions of PERK, eIF2α peaked at 24 h, while ATF4 and CHOP peaked at 12 h in ox-LDL group and aspirin+ox-LDL group. Compared with control group, the expressions of PERK, eIF2α, ATF4 and CHOP were significantly higher in ox-LDL group at each times (all P<0.05). Compared with ox-LDL group, the expressions of the above indicators were significantly lower in aspirin+ox-LDL group at each times (all P<0.05). At 24 h, compared with control group, the expressions of p-PERK and p-eIF2α were significantly higher in ox-LDL group (both P<0.05). Compared with ox-LDL group, the expressions of p-PERK and p-eIF2α were significantly lower in aspirin+ox-LDL group (both P<0.05). At 12 h, the expression of ATF4 protein in each group was similar to that of mRNA. There were no significant difference in the expressions of all indicators between aspirin group and control group.
Conclusions:Hyperlipidemia may cause endoplasmic reticulum stress in podocytes by inducing phosphorylation of PERK and eIF2α, activating ATF4 transcription and inducing high expression of CHOP. Aspirin may partially block the PERK pathway, which may have protective effects for podocytes.
