Progesterone Reduces ATP-Induced Pyroptosis of SH-SY5Y Cells

Aim. To investigate the mechanism of progesterone inhibiting the scorch death of SH-SY5Y cells induced by exogenous adenosine triphosphate (ATP). Methods. SH-SY5Y cells with good logarithmic growth were used in the experiment. The cells were randomly divided into 5 groups: normal control group, DMSO group, BBG group, ATP group, and ATP+progesterone group. The cell survival rate of each group was measured by CCK-8 method. The expressions of P2X(7) receptor, caspase-1, caspase-11, and IL-1 beta were detected by western blotting. Results. (1) After SH-SY5Y cells were treated with ATP at different concentrations (1, 3, 6, and 9 mmol/L) for 2 hours, the cell survival rate decreased in a concentration-dependent manner compared with the normal blank group. The results showed that the optimal lethal concentration of ATP was 6 mmol/L. SH-SY5Y cells were preincubated with progesterone at different concentrations (3, 10, 30, and 100 nmol/L) for 30 minutes and then incubated with 6 mmol/L ATP. The cell survival rate of this group was significantly improved (P < 0.01). The optimal concentration of progesterone to improve cell survival and inhibit cell death was 30 nmol/L. (2) Compared to the control group, there was no significant difference (P > 0.05) in P2X(7) receptor, caspase-1, caspase-11, and IL-1 beta with the DMSO group (0.001% DMSO, 24 h) and BBG group (bbg1 mmol/L, 24 h). (3) In the ATP group, the expression of P2X(7) receptor and caspase-1 (the key protein of classical cell death pathway) increased significantly (P < 0.01), which was related to inflammatory factor IL-1 beta with consistent performance (P < 0.01). There was no significant change in caspase-11 (the key protein of nonclassical focal death pathway) (P > 0.05). (4) The expression of P2X(7) receptor, caspase-1, and inflammatory factor IL-1 beta in the progesterone+ATP group was significantly downregulated (P < 0.01). There was no significant change in caspase-11 (P > 0.05). Conclusion. Certain dose of progesterone can inhibit the focal death of SH-SY5Y cells induced by extracellular high concentration ATP. It can reduce the expression of P2X(7) receptor, inhibit the conduction pathway of cell death, reduce the release of inflammatory factor IL-1 beta, and improve cell survival.

Automated summary

This study aimed to investigate the mechanism of progesterone inhibiting the scorch death of SH-SY5Y cells induced by exogenous adenosine triphosphate (ATP). The results showed that progesterone can improve cell survival and inhibit cell death by reducing the expression of P2X(7) receptor, inhibiting the conduction pathway of cell death, and reducing the release of inflammatory factor IL-1 beta.