USP13 reduces septic mediated cardiomyocyte oxidative stress and inflammation by inducing Nrf2

Main Article Content

Danyang Wu
Rong Yuan
Lian Zhang
Meng Sun

Keywords

Cardiovascular Disease, LPS, Nrf2, Septic Shock, USP13

Abstract

Background: Sepsis is a common cardiovascular complication that can cause heart damage. The regulatory role of ubiquitin-specific peptidase 13 (USP13) on erythroid 2–related factor 2 (Nrf2) has been reported, but its regulatory role in septic cardiomyopathy remains unclear.


Methods: The Sprague Dawley (SD) rat model of septic myocardial injury was constructed by lipopolysaccharides (LPS). The serum lactate dehydrogenase (LDH) and creatine kinase (CK) levels were detected, the mRNA and protein expression levels of Nrf2 and USP13 in tissues were detected by real-time quantitative reverse transcription PCR (qRT-PCR) and western blot (WB), and the expression of USP13 at the treatment time of 3 h, 6 h, and 12 h was also detected. The cell viability and USP13, Nrf-2 and heme oxygenase-1 (HO-1) expression levels of H9C2-treated cells by LPS and the oxidative stress level and inflammatory response of H9C2 cells were detected by enzyme-linked immunosorbent assay (ELISA) and WB.


Results: The results showed that USP13 was downregulated in septic myocardial injury tissues, and the Nrf2 level was increased in vitro after the cells were treated with LPS. Overexpression of USP13 further induced Nrf2 to reduce apoptosis, oxidative stress, and expression of inflammatory factors.


Conclusion: In conclusion, this study demonstrated that USP13 was downregulated in septic myocardial injury tissues, and USP13 overexpression increased Nrf2 levels and reduced apoptosis. Further studies showed that USP13 reduced LPS-induced oxidative stress and inflammation by inducing Nrf2.

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