Alleviation of sepsis‑induced cardiac dysfunction by overexpression of Sestrin2 is associated with inhibition of p‑S6K and activation of the p‑AMPK pathway.

Abstract

Sepsis‑induced myocardial injury is one of the manifestations of multiple organ dysfunction in sepsis. The aim of the present study was to determine the mechanism of alleviation of lipopolysaccharide (LPS)‑induced injury on cardiomyocytes by Sestrin2. A sepsis model using LPS injection was constructed in Sprague‑Dawley (SD) rats, and after 6, 12 and 24 h, rat blood was collected and cardiac troponin T (CTnT) levels were determined using ELISA. Heart specimens were excised, tumor necrosis factor‑α (TNF‑α) and interleukin 6 (IL‑6) levels were detected by ELISA, malondialdehyde (MDA) levels were estimated using colorimetric analysis, and phosphorylated (p)‑S6K and p‑AMP‑activated protein kinase (AMPK) levels were determined by western blot analysis. In the septic rats, phenomenon of myocardial fiber rupture, interstitial edema and inflammatory cell infiltration were observed under light microscope. Following LPS injection, CTnT in serum and MDA in myocardial homogenate were increased time‑dependently. TNF‑α and IL‑6 levels were significantly increased, with a peak at 6 h. p‑S6K levels were adaptively downregulated, and levels of p‑AMPK and Sestrin2 were adaptively upregulated by LPS. In LPS‑injured H9c2 cells, Sestrin2 overexpression attenuated the LPS‑mediated inhibitory effects on cell viability, suppressed LPS‑mediated increase in CTnT, TNF‑α, IL‑6 and MDA levels, as well as attenuated p‑S6K levels and elevated p‑AMPK and Sestrin2 levels. Sestrin2 interference showed the opposite effect. Sestrin2 promoted cell viability and inhibited the inflammatory responses of LPS‑injured myocardial cells. The phenomena may be associated with inhibition of p‑S6K and activation of the p‑AMPK pathway.

• Authors: Ziwen Wang, Lin Bu, Peng Yang, Shoujie Feng, Feng Xu
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 20 Issue 3 Pg. 2511-2518 (Sep 2019) ISSN: 1791-3004 [Electronic] Greece
• PMID: 31524263 (Publication Type: Journal Article)

Chemical References

• Lipopolysaccharides
• Nuclear Proteins
• Sesn2 protein, rat
• Ribosomal Protein S6 Kinases, 70-kDa
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (metabolism)
• Animals
• Cell Survival (drug effects)
• Female
• Gene Expression
• Heart Diseases (etiology, metabolism, physiopathology)
• Lipopolysaccharides (pharmacology)
• Myocardium (metabolism)
• Myocytes, Cardiac (drug effects, metabolism)
• Nuclear Proteins (genetics)
• Rats
• Ribosomal Protein S6 Kinases, 70-kDa (metabolism)
• Sepsis (complications)
• Signal Transduction (drug effects)