Serum proteomics analysis in time-dependent septic prognosis in mice

CAMILA A SENNA; DIEGO A GOLOMBEK; IGNACIO AIELLO; MALENA L MUL FEDELE; NATALIA PALADINO

Florida

Congreso; 2022 Conference - Society for Research on Biological Rhythms; 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) 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 markers 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 and 235 in LPS ZT11 and ZT19. We analyzed the relative amount of these 243 proteins using two-way ANOVA and observed 16 proteins which exhibited diurnal changes in the VEH samples (4 upregulated at ZT11 and 12 upregulated at ZT19) and 6 proteins which changed after LPS inoculation at both times (5 upregulated and 1 down regulated by LPS). In addition, 25 proteins showed a time-dependent response to LPS (10 upregulated and 5 downregulated at ZT11, 6 upregulated and 4 downregulated at ZT19). Several proteins upregulated at ZT11 are involved in immune response, cell communication, migration and adhesion, coagulation and cell death processes. While proteins downregulated at ZT11 are involved in metabolic processes, coagulation and immune response. On the other hand, several proteins upregulated at ZT19 are related to nutrient metabolism and/or catabolic process. Lastly, one protein downregulated at ZT19 is a negative regulator of catabolic process and coagulation, and another one participates in the response to cytokines and glucocorticoids, and regulates cell communication, adhesion and migration. In conclusion, activation of the coagulation cascade and immune response seems to be associated with a worse prognosis at ZT11 while catabolic processes appear to be induced at the time of better prognosis (ZT19).