Role of autophagy in the motivation of rat myocardial hypertrophy in H9c2 cells induced by bone morpho-genetic protein 4 and its mechanism
10.16571/j.cnki.1008-8199.2016.07.010
- VernacularTitle:细胞自噬在骨形成蛋白4促大鼠 H9 C2心肌细胞肥大中的作用及机制
- Author:
Yezhen TAO
;
Jianhua LI
;
Yakun LIU
;
Peipei WANG
;
Yu YUAN
- Publication Type:Journal Article
- Keywords:
Autophagy;
Extracellular signal regulating kinase (ERK1/2) signal transduction pathway;
Bone morphogenetic protein 4;
Myocardial cells;
Hypertrophy
- From:
Journal of Medical Postgraduates
2016;29(7):718-722
- CountryChina
- Language:Chinese
-
Abstract:
Objective Bone morphogenetic protein 4 ( BMP4) induces rat myocardial hypertrophy in H9c2 cells, but the spe-cific mechanism remains unclear .The study aimed to elucidate the role of autophagy in myocardial hypertrophy and its relationship with extracellular signal regulating kinase ( ERK1/2) signal transduction pathway . Methods H9c2 cardiomyocytes were randomly divided into 4 groups:control group, BMP4 group, BMP4+PD98059 (ERK1/2 signal pathway inhibitor) group and BMP4+3MA (autophagy inhibitor) group.With PD98059(50μmol/L) and 3MA(5mmol/L) blocking for 30min, BMP4 (50μg/L) were added.Expressions of tiny tube related proteins 1 light chain 3 (LC3) and p-ERK1/2 were detec-ted after culturing for 30min.48h later, measurements were made on cell surface area , average protein content and α-smooth muscle actin (α-SMA ) protein expression level .Cell morphology and size were measured respectively by inverted microscope and Image J software .Total protein content was detected by BCA , and western blot was used to measure the expressions of LC3, ERK1/2, p-ERK1/2 and α-SMA. Resul ts 30min later, the expressions of LC3 and p-ERK1/2 were significantly higher in BMP4 group than in control group [(1.54 ±0.05) vs (1.95 ±0.11),(0.94 ±0.04) vs (1.33 ± 0.06),P<0.01] and no significant difference was found in other two groups .Compared with BMP4 group, significant decrease was found in BMP4+PD98059 and BMP4+3MA [(1.95 ±0.11) vs (1.59 ±0.08), (1.36 ±0.02);(1.33 ±0.06) vs (0.87 ±0.05), (0.95 ±0.15), P<0.01], while no significant difference was found between BMP 4+PD98059 group and BMP4+3MA group.48h lat-er, the cell area, protein content and α-SMA protein expression level are significantly lower in control group than in BMP 4 group [(644.1 ±15.01)μm2 vs (745.6 ±14.43)μm2,(240.0 ±7.26)pg/cell vs (347.1 ±5.4)pg/cell,(1.22 ±0.06 vs 1.99 ±0.03),P<0.01], while the corresponding indexes were significantly higher in BMP 4+PD98059 and BMP4+3MA compared with BMP4 group [(745.6 ±14.43)μm2 vs (645.0 ±12.63)μm2, (647.7 ±13.89)μm2;(347.1 ±5.4)pg/cell vs (239.7 ±3.39)pg/cell , (241.1 ± 8.56)pg/cell;(1.99 ±0.03) vs (1.13 ±0.05);(1.12 ±0.02), P<0.01].No significant difference was found as to the indexes be-tween BMP4+PD98059 group and BMP4+3MA group(P>0.05). Conclusion Autophagy may participate in BMP4-induced rat myo-cardial hypertrophy in H9c2 cells through ERK1/2 signal transduction pathway .The clinical treatment of myocardial hypertrophy may benefit from the blocking of autophagy or ERK 1/2 signal transduction pathway .