Role and related mechanism of S1P/S1P1 signal pathway during post conditioning of hypertrophic cardiomyocytes
10.3760/cma.j.issn.0253-3758.2016.05.013
- VernacularTitle:一磷酸鞘氨醇/一磷酸鞘氨醇1受体信号通路在大鼠肥大心肌细胞缺血后适应中的作用及其机制
- Author:
Xinhui BAO
1
;
Haixia LI
;
Jing TAO
;
Xiaomei LI
;
Yining YANG
;
Yitong MA
;
Bangdang CHEN
Author Information
1. 新疆医科大学第一附属医院心脏中心
- Keywords:
Myocardial reperfusion;
Receptors,lysosphingolipid;
Apoptosis
- From:
Chinese Journal of Cardiology
2016;44(5):431-435
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the role and mechanism of sphingosine-l-phosphate (S1P)/sphingosine-1-phosphate receptor 1 (S1P1) signal pathway during post conditioning of hypertrophic cardiomyocytes.Methods Neonatal rat cardiomyocytes were isolated and cultured,then stimulated by norepinephrine (NE) to induce cardiomyocytes hypertrophy.Using tri-gas incubator to create hypoxia and reoxygenation enviroment to mimic ischemia-reperfusion and postconditioning.Hypertrophic cardiomyoctyes were divided into five groups according to the presence or absence of various drugs and postconditiong and relevant signal pathways changes were detected:(1) IPost group (hypoxia + postconditioning);(2) IPost + S1P group (cells were pretreated with S1P (1 μmol/L) for 2 h before IPost);(3) IPost + W-146 + S1P group (cells in IPost + W-146 + S1P group were pretreated with S1P1 inhibitor W-146 (0.4 μmol/L) for 20 min);(4) IPost + PD98059 + S1P group (cells in IPost + S1P group were pretreated with MAPK antagonist PD98059 (125 μmo[/L) for 20 min);(5) IPost + LY-294002 + S1P group (cells in IPost + S1P group were pretreated with PI3K antagonist LY294002 (0.1 μmol/L) for 20 min).Apoptosis was detected by flow cytometry and protein expression of relevant signal pathways were detected by Western blot.Results (1) Apoptosis rate was significantly increased in hypoxia/reoxygenation (27.90 ± 4.49) ％ group compared with normal control group (7.97 ± 2.18) ％,which could be significantly reduced in IPost group (15.90 ± 1.77) ％ (all P ＜ 0.05).(2) Apoptosis rate and caspase-3 expression were both significantly lower in IPost + S1P and IPost + S1P + LY-294002 groups than in IPost and IPost + S1P + W-146 and IPost + S1P + PD98059 group (all P ＜ 0.05).(3)p-ERK1/2 expression was significantly higher in IPost + S1P and IPost + S1P + LY-294002 group than in IPost and IPost + SIP + W-146 group and IPost + S1P + PD98059 group (all P ＜ 0.05) while p-Akt expression was similar among IPost,IPost + S1P + W-146 and IPost + S1P +PD98059 groups.p-ERK1/2 and p-Akt levels in IPost + S1P + W-146 group and IPost + S1P + PD98059 were similar as in IPost group.Conclusions S1P can play protective role on NE induced cardiomyocytes hypertrophy during post conditioning through downregulating caspase-3 expression and reducing apoptosis rate via targeting S1P1 and activating ERK1/2 signal pathway.
