Figure 6.
Methionine cycle recovery rewires nitrogen homeostasis from urea cycle to polyamine synthesis. (A) Schematic representation and determination of metabolites from methionine metabolism and polyamine synthesis in primary hepatocytes treated with 13C–methionine and 10 mM acetaminophen (APAP) at different times (1 and 3 h) and an anti-miR-873-5p or an unrelated control (miR-Ctrl): methionine (Met), S-adenosylmethionine (AdoMet), decarboxy-S-adenosylmethionine (dc-AdoMet), MTA, spermidine (Spd), spermine (Spm) and N-acetylspermine (Spm-NAc). (B) Schematic representation of TUNEL determination of primary hepatocytes treated for 6 h with 10mM APAP, an anti-miR-873-5p or miR-Ctrl and (C) different concentrations of ammonium chloride (1 mM and 2.5 mM NH4Cl) or (D) 1 μM SAM486A or 0.5 μM DFMO. * p < 0.05, ** p < 0.01, **** p < 0.0001 are shown.