Effects of PI3K/AKT signaling mediated by mercaptopyruvate sulfurtransferase on apoptosis and autophagy in acute pancreatitis cell model

Objective To investigate the effect of mercaptopyruvate thiotransferase (MPST) mediated PI3K/AKT signaling on apoptosis and autophagy in acute pancreatitis (AP) cell model.

Methods An AP in vitro cell model was constructed.Cells were divided into CON group, AP group, AP+siMPST group, and AP+oeMPST group.CCK-8 method was used to detect cell viability.The levels of inflammatory cytokines TNF-α, IL-1 and IL-6 were detected by ELISA.Flow cytometry was used to detect the level of apoptosis.Western blotting was used to detect the expression levels of LC3 Ⅱ/Ⅰ, beclin1, ATG5, MPST, PI3K, p-PI3K, AKT, and p-AKT in acinar cells.

Results The cell survival rates of the AP group, AP+siMPST group, and AP+oeMPST group were all lower than those of the CON group (P < 0.01), while the apoptosis rate was higher than that of the CON group (P < 0.01);The cell survival rate of the AP+siMPST group and the apoptosis rate of the AP+oeMPST group were higher than those of the AP group (P < 0.01), while the apoptosis rate of the AP+siMPST group and the cell survival rate of the AP+oeMPST group were lower than those of the AP group (P < 0.01).The levels of TNF-α, IL-1, IL-6, LC3 Ⅱ/Ⅰ, beclin1, ATG5, MPST, p-PI3K/PI3K, and p-AKT/AKT in acinar cells of AP group and AP+oeMPST group were significantly higher than in the CON group (P < 0.01).The above indicators were lower in the AP+siMPST group than in the AP group (P < 0.01), while the AP+oeMPST group was higher than in the AP group (P < 0.01).

Conclusions MPST can induce pancreatic acinar cell apoptosis, autophagy, and inflammatory response through PI3K/AKT signaling.Inhibiting MPST may have therapeutic significance for AP.