Antophagy inhibition can decrease AR42J cell apoptosis induced by exendin-4 / 中华肝胆外科杂志
Chinese Journal of Hepatobiliary Surgery
; (12): 848-852, 2018.
Article
ي Zh
| WPRIM
| ID: wpr-734389
المكتبة المسؤولة:
WPRO
ABSTRACT
Objective To explore whether exendin-4 inhibits AR42J cells and its mechanism.Methods AR42J cells were treated with exendin-4 under multiple concentrations(1,5,10 pmol/L) at 24,48,72,96,120 h to assess its cell viability by MTT assay and got the IC-50 and time points.Then checking whether exendin-4 could induce the AR42Jcells apoptosis by setting normal control (NC) group,exendin-4 (Ex-4) group and Ex-4+ z-VAD-fmk (apoptosis inhibitor) group,and exploring whether 3-MA which is autophagy inhibitor could inhibit the AR42J cells apoptosis induced by exendin-4 by setting NC group,Ex-4 group and Ex-4+3-MA group.Cell viability was analyzed by MTT and the cells apoptosis was detected by flow cytometry and the protein levels of caspase-3,LC3 and p62 were studied by Western blot.Results Concentration of 10 pmol/L exendin-4 and and time point 72 h were selected for the further study.z-VAD-fmk pretreatment can significantly inhibit the cell viability of exendin-4 by (81.2±3.3)% vs.(49.4±3.0)% (P<0.05).Flow cytometry showed that exendin-4 could induce the AR42J cells apoptosis by (28.2± 1.4)% vs.(3.6±0.8)%,and increased the caspase-3 level by Western blot,which both can be reversed by (79.1 ±2.3) % vs.(49.8±2.5)% (P<0.05) when the cells were treated for 72 h,as was apoptosis ratio by (14.5±2.1)% vs.(29.2±3.2)%.Western blot showed that exendin-4 can upregulate protein levels of LC3B-Ⅱ,p62 和 caspase-3 and 3-MA,and pretreatment can inhibit the upregulation of LC3B-Ⅱ and caspase-3 but further increased the upregulation of p62 induced by exendin-4.Conclusions Exendin-4 can induce AR42J cells apoptosis and 3-MA pretreating can inhibit exendin-4 cytotoxicity through downregulating autophagy.So auto phagy inhibitor 3-MA could potentially extenuate the cytotoxicity of exendin-4 in pancreatic acinar cells.
النص الكامل:
1
الفهرس:
WPRIM
اللغة:
Zh
مجلة:
Chinese Journal of Hepatobiliary Surgery
السنة:
2018
نوع:
Article