Serum proteomic analyze reveal different biologic process associated with time-dependent septic prognosis in mice

SENNA, CAMILA AGUSTINA; MUL FEDELE, MALENA LIS; AIELLO, IGNACIO; GOLOMBEK, DIEGO ANDRES; PALADINO, NATALIA

Conferencia; Society for Research on Biological Rhythms Meeting; 2022

Society for Research on Biological Rhythms

Sepsis is a syndrome caused by a deregulated host response to pathogens, representing the primary cause of death from infection. In patients undergoing sepsis, deregulated circadian rhythms have been reported. Moreover, in animal models, the mortality rate due to septic shock is strongly dependent on the circadian system: mice injected intraperitoneally with high doses of LPS (close to 20 mg/kg) at the end of the day ⦏ZT11 (ZT0: time of lights on; ZT12: time of lights off)⦎ show a higher mortality rate (80% approximately) than those injected in the middle of the night (ZT19; 30% approximately). In order to evaluate serum proteins which could be useful as a prognosis marker and/or to find new insights involved in this pathology, we performed a proteomic analysis from serum samples obtained from mice inoculated with LPS or vehicle (VEH) at ZT11 or ZT19. We found 243 proteins, of which 231 were present in VEH ZT11 and ZT19 (not exactly the same) and 235 in LPS ZT11 and ZT19 (not exactly the same). We analyzed the relative amount of these 243 proteins using two-way ANOVA and observed 16 proteins which change according to the time in the VEH samples (4 upregulated at ZT11 and 12 upregulated at ZT19) and 6 proteins which changes after LPS inoculation at both times (5 upregulated and 1 down regulated by LPS). In addition, 25 proteins showed a significant interaction factor in the ANOVA test, which exhibit different patterns on their expression. Four out of six proteins upregulated at ZT19 are related to nutrient metabolism and/or catabolic process. Of the four proteins downregulated at ZT19, one is a negative regulator of catabolic process and coagulation, and another participates in the response to cytokines and glucocorticoids, and regulates cell communication, adhesion and migration. On the other hand, seven out of ten proteins upregulated at ZT11 are involved in immune response, cell communication, migration and adhesion, coagulation and cell death process. Four out of five proteins downregulated at ZT11 are involved in metabolic process, coagulation and immune response. In conclusion, activation of the coagulation cascade and immune response seems to be associated with a worse prognosis at ZT11 and the catabolic process seems to be induced at the time of better prognosis (ZT19).