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

Angiotensin-(1-7) attenuates caerulein-induced pancreatic acinar cell apoptosis
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血管紧张素 – (1 – 7) 减弱雨蛙素 – 诱导的胰腺腺泡细胞凋亡

DOI:
10.3892/mmr.2017.6982
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发表时间:
2017-09-01
影响因子:
3.4
通讯作者:
Wang, Chao
Wang, Chao
中科院分区:
医学4区
文献类型:
--
作者:
Cui, Lijian;Liu, Ruixia;Wang, Chao

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胰腺腺泡细胞广泛凋亡是急性胰腺炎(AP)的常见病理现象,与胰腺实质细胞减少及胰腺损伤密切相关。本研究旨在探讨血管紧张素(Ang)-(1-7)对雨蛙肽(CAE)诱导胰腺腺泡细胞凋亡的影响。将小鼠胰腺腺泡癌细胞(MPC-83)分为4组:对照组、CAE组、CAE + Ang-(1-7)组和CAE + Ang-(1-7)拮抗剂(A779)组。对照组为正常MPC-83细胞,不作特殊处理。CAE组用10 nmol/l CAE刺激,分别于2、6、12、24和48 h取材。CAE + Ang-(1-7)组和CAE + A779组分别用不同浓度的Ang-(1-7)或A779(10(-7)、10(-6)或10(-5)mol/l)预处理30 min。因为它部分或完全负责许多关键蛋白质的蛋白水解切割,包括核酶聚(ADP-核糖)聚合酶。半胱天冬酶-3的活化需要将其失活的酶原蛋白水解加工成活化的p17和p12片段。因此,本研究探讨了凋亡标志物,包括裂解的caspase-3,B细胞淋巴瘤2(Bcl-2),Bcl-2样蛋白4(Bax)和肾素-血管紧张素系统(RAS)途径相关蛋白(ACE 2和Mas受体)。结果显示,CAE组caspase-3酶切水平明显高于对照组(P
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