Extended Data Fig. 2: PEP inhibits the activation of cGAS-STING pathway during cell senescence by disrupting the formation of cGAS-DNA complex. | Nature Aging

Extended Data Fig. 2: PEP inhibits the activation of cGAS-STING pathway during cell senescence by disrupting the formation of cGAS-DNA complex.

From: The glycolytic metabolite phosphoenolpyruvate restricts cGAS-driven inflammation to promote healthy aging

Extended Data Fig. 2: PEP inhibits the activation of cGAS-STING pathway during cell senescence by disrupting the formation of cGAS-DNA complex.

(a) Immunoblot of Pkm in BMDMs from Pkmfl/fl-LysMcre−/− (n = 5), Pkmfl/fl-LysMcre+/− (n = 5) or Pkmfl/fl-LysMcre+/+ (n = 6) mice. (b) The effect of PKM knockout on the activation of cGAS-STING pathway. Immunoblot of p-IRF3 in BMDMs from Pkmfl/fl-LysMcre−/−, Pkmfl/fl-LysMcre+/−or Pkmfl/fl-LysMcre+/+ mice upon HT-DNA transfection. (c) Heatmap showing levels of glycolytic metabolites in senescent WI-38 cell upon PEP or vehicle (Veh) treatment measured by LC-MS. (d) The effect of PEP on HT-DNA-induced the cGAMP synthesis in THP-1 cells. (n = 3). (e) Experimental workflow of Sepharose and PEP coupled. (f) Quantification of cGAS foci in THP-1 cells transfected with HT-DNA (2 μg·ml−1) for 3 h with PEP or vehicle (Veh) treatment. (n = 3). (g,h) Cytokine-array analysis of secreted factors in replication-induced senescent WI-38 cells treated with PEP or vehicle (Veh). (n = 2). Data show the mean ± SD; Each dot represents one independent biological replicate; One-way ANOVA with Turkey post hoc test in (d); Two-way ANOVA with Sidak post hoc test in (f); Two-tailed unpaired t test in (h).

Source data

Back to article page