Time of day-dependent alterations of ferroptosis in LPS-induced myocardial injury via Bmal-1/AKT/ Nrf2 in rat and H9c2 cell.
Heliyon
; 10(17): e37088, 2024 Sep 15.
Article
en En
| MEDLINE
| ID: mdl-39296207
ABSTRACT
Background:
One of the most prevalent causes of death in sepsis is sepsis-induced cardiomyopathy (SICM). Circadian disruption is involved in the progress of sepsis. However, the molecular mechanism remains unclear.Methods:
Here, we built LPS-induced SICM in-vivo and in-vitro models. LPS was administrated at the particular Zeitgeber times (ZT), ZT4-ZT10-ZT16-ZT22 and ZT10-ZT22 in vivo and vitro experiments, respectively.Results:
In vivo experiment, injection of LPS at ZT10 induced higher infiltration of inflammatory cells and content of intracellular Fe2+, and lower level of Glutathione peroxidase 4 (GPX4) and cardiac function than other ZTs (P < 0.05), which indicated that myocardial ferroptosis in septic rat presented a time of day-dependent manner. Bmal-1 protein and mRNA levels of injection of LPS at ZT10 were lower than those at other three ZTs (P < 0.05). The ratios of pAKT/AKT at ZT4 and ZT10 LPS injection were lower than those at ZT16 and ZT22 (P < 0.05). Nrf2 protein levels at ZT10 LPS injection were lower than those at other three ZTs (P < 0.05). These results indicated that the circadian of Bmal-1 and its downstream AKT/Nrf2 pathway in rat heart were inhibited under SICM condition. Consistent with in-vivo experiment, we found LPS could significantly reduce the expressions of Bmal-1 protein and mRNA in H9c2 cell. Up-regulation of Bmal-1 could reduce the cell death, oxidative stress, ferroptosis and activation of AKT/Nrf2 pathway at both ZT10 and ZT22 LPS administration. Conversely, its down-regulation presented opposite effects. AKT siRNA could weaken the effect of Bmal-1 pcDNA.Conclusion:
Ferroptosis presented the time of day-dependent manners via Bmal-1/AKT/Nrf2 in vivo and vitro models of SICM.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Heliyon
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Reino Unido