Role of protein kinase Cα/heme oxygenase-1 signaling pathway in LPS-caused damage to type Ⅱ alveolar epithelial cells of rats: the relationship with mitochondrial fusion
10.3760/cma.j.issn.0254-1416.2018.11.028
- VernacularTitle:PKCα/HO-1信号通路在LPS致大鼠肺泡Ⅱ型上皮细胞损伤中的作用:与线粒体融合的关系
- Author:
Yanmin ZHAO
1
;
Jia SHI
;
Jianbo YU
;
Yuan ZHANG
;
Lirong GONG
;
Shu'an DONG
Author Information
1. 300100,天津医科大学南开临床学院天津市南开医院麻醉科
- Keywords:
Protein kinase c-alpha;
Heme oxygenase-1;
Lipopolysaccharides;
Epithelial cells;
Pulmonary alveoli;
Mitochondrial fusion
- From:
Chinese Journal of Anesthesiology
2018;38(11):1384-1387
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the role of protein kinase Cα (PKCoα)/heme oxygenase-1 (HO-1) signaling pathway in lipopolysaccharide (LPS)-caused damage to type Ⅱ alveolar epithelial cells of rats and the relationship with mitochondrial fusion.Methods Type Ⅱ alveolar epithelial cells were seeded in 96-well plates at a density of 2× 105 cells/ml and divided into 5 groups (n =40 each) using a random number table method:control group (group C),Go6976 group (group G),LPS group (group L),LPS plus PKCα inhibitor Go6976 group (group LG) and LPS plus dimethyl sulfoxide (DMSO) group (group LD).Group LG and group LD were pretreated with 5 μmol/L Go6976 and the equal volume of 0.1％ DMSO,respectively,for 30 min,lipopolysaccharide (LPS) 10 μg/ml was then given to establish the model of type Ⅱ alveolar epithelial cell damage in L,LG and LD groups,Go6976 5 μmol/L was added in group G,and the equal volume of phosphate buffer solution was added in group C.The cells were collected after 24 h of incubation for measurement of malondialdehyde (MDA) and reactive oxygen species (ROS) contents,superoxide dismutase (SOD) activity and expression of PKCα,HO-1,mitochondrial fusion-related proteins 1 and 2 (Mfn1,Mfn2),optic atrophy 1 (OPA1) protein and mRNA (by fluorescent quantitative polymerase chain reaction or Western blot).Results Compared with group C,MDA and ROS contents were significantly increased,the SOD activity was decreased,the expression of PKCα and HO-1 protein and mRNA was up-regulated,and the expression of Mfn1,Mfn2 and OPA1 protein and mRNA was downregulated in L,LG and LD groups (P＜0.05),and no significant change was found in the parameters mentioned above in group G (P＞0.05).Compared with group L,MDA and ROS contents were significantly increased,the SOD activity was decreased,and the expression of PKCα,HO-1,Mfn1,Mfn2 and OPA1 protein and mRNA was down-regulated in group LG (P＜0.05),and no significant change was found in the parameters mentioned above in group LD (P＞0.05).Conclusion Activation of PKCα/HO-1 signaling pathway is the endogenous protective mechanism of LPS-caused damage to type Ⅱ alveolar epithelial cells,which may be related to promoting mitochondrial fusion in rats.
