Angiotensin-(1-7) attenuates caerulein-induced pancreatic acinar cell apoptosis

作者：Cui, Lijian; Liu, Ruixia; Li, Chunyun; Yu, Xiaozheng; Liu, Xiaoya; Hou, Fei; Chi, Cheng; Yin, Chenghong^*; Wang, Chao^*

来源：Molecular Medicine Reports, 2017, 16(3): 3455-3460.

DOI：10.3892/mmr.2017.6982

• angiotensin-(1-7)
• apoptosis
• caspase-3
• B-cell lymphoma 2
• bcl-2-like protein 4
• angiotensin-converting enzyme 2
• Mas receptor

Extensive apoptosis of pancreatic acinar cells frequently occurs in acute pancreatitis (AP), and has been identified to be closely associated with the decrease of pancreatic parenchymal cells and pancreatic damage. The present study aimed to investigate the possible effect of angiotensin (Ang) -(1-7) on caerulein (CAE)-induced pancreatic acinar cell apoptosis. Mouse pancreatic acinar cancer cells (MPC-83) were divided into 4 groups: Control group; CAE group; CAE + Ang-(1-7) group; and CAE + Ang-(1-7) antagonist (A779) group. The control group consisted of normal MPC-83 cells without special treatment. The CAE group was stimulated with 10 nmol/l CAE and harvested at 2, 6, 12, 24 and 48 h. For the CAE + Ang-(1-7) group and CAE + A779 group, the CAE-induced pancreatic acinar cells were mock pretreated or pretreated with different concentrations of Ang-(1-7) or A779 (10(-7), 10(-6) or 10(-5) mol/l) for 30 min. Caspase-3 is a critical executioner of apoptosis, as it is either partly or completely responsible for the proteolytic cleavage of numerous key proteins including the nuclear enzyme poly (ADP-ribose) polymerase. Activation of caspase-3 requires proteolytic processing of its inactive zymogen into activated p17 and p12 fragments. Thus, the present study investigated the apoptotic markers, including cleaved caspase-3, B-cell lymphoma 2 (Bcl-2), Bcl-2-like protein 4 (Bax) and renin-angiotensin system (RAS) pathway related proteins (ACE2 and Mas receptor). The results demonstrated that the cleaved caspase-3 levels were increased in the CAE group (P<0.05), peaking at 24 h, and declined when incubated with Ang-(1-7). Following treatment with Ang-(1-7), levels of the anti-apoptotic protein Bcl-2 rose dramatically in a dose-dependent manner. The ratio of the pro-apoptotic protein Bax to the anti-apoptotic protein Bcl-2 dropped notably, which demonstrated a tendency towards curbing apoptosis. In addition, the cleaved caspase-3 levels, and the ratio of Bax to Bcl-2 in the CAE + A779 group presented a significant rise compared with the CAE group. It was concluded that Ang-(1-7) may possess an inhibitory effect on CAE-induced pancreatic acinar cell apoptosis and that appropriate interventions in RAS may attenuate pancreatic injury during AP.

• 出版日期2017-9
• 单位首都医科大学