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. 2023 Aug;46(4):1133-1143.
doi: 10.1007/s10753-023-01804-7. Epub 2023 Apr 13.

LPS-aggravated Ferroptosis via Disrupting Circadian Rhythm by Bmal1/AKT/p53 in Sepsis-Induced Myocardial Injury

Hao Lin  1 , Fang Ji  2 , Kong-Qin Lin  1 , Yu-Tao Zhu  1 , Wen Yang  1 , Long-Hai Zhang  2 , Jian-Gao Zhao  3 , Ying-Hao Pei  4
Affiliations

LPS-aggravated Ferroptosis via Disrupting Circadian Rhythm by Bmal1/AKT/p53 in Sepsis-Induced Myocardial Injury

Hao Lin et al. Inflammation. 2023 Aug.

Abstract

Circadian disruption is involved in the progress of sepsis-induced cardiomyopathy (SICM), one of the leading causes of death in sepsis. The molecular mechanism remains ambiguous. In this study, LPS was used to build SICM model in H9c2 cell. The results suggested that LPS induced cytotoxicity via increasing ferroptosis over the time of course. After screening the expressions of six circadian genes, the circadian swing of Bmal1 was dramatically restrained by LPS in H9c2 cell of SIMC vitro model. PcDNA and siRNA were used to upregulate and downregulate Bmal1 and confirmed that Bmal1 inhibited LPS-triggered ferroptosis in H9c2 cells. Then, the results suggested that AKT/p53 pathway was restrained by LPS in H9c2 cell. Rescue test indicated that Bmal1 inhibited LPS-triggered ferroptosis via AKT/p53 pathway in H9c2 cells. In summary, our findings demonstrated that LPS induced cytotoxicity via increasing ferroptosis over the time of course in H9c2 cells and Bmal1 inhibited this toxicity of LPS via AKT/p53 pathway. Although further studies are needed, our findings may contribute to a new insight to mechanism of SICM.

Keywords: Bmal1/AKT/p53; LPS; disrupting circadian rhythm; ferroptosis; sepsis-induced myocardial injury..

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