H2S attenuates sepsis‑induced cardiac dysfunction via a PI3K/Akt‑dependent mechanism

Abstract

The heart is the most vulnerable target organ in sepsis, and it has been previously reported that hydrogen sulfide (H 2 S) has a protective role in heart dysfunction caused by sepsis. Additionally, studies have demonstrated that the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway has a protective function during sepsis. However, the potential association between H 2 S and PI3K/Akt in sepsis-induced cardiac dysfunction is unclear. Therefore, the PI3K inhibitor LY294002 was used to investigate the role of PI3K/Akt signaling in the protective effects of H 2 S during sepsis-induced myocardial injury. A rat sepsis model was established using cecal ligation and puncture (CLP) surgery. Sodium hydrosulfide, a H 2 S donor, was administered intraperitoneally (8.9 µmol/kg), and serum myocardial enzyme levels, inflammatory cytokine levels, cardiac histology and cardiomyocyte apoptosis were assessed to determine the extent of myocardial damage. The results demonstrated that exogenous H 2 S reduced serum myocardial enzyme levels, decreased the levels of the inflammatory factors tumor necrosis factor (TNF)-α and interleukin (IL)-6, and increased the level of anti-inflammatory IL-10 following CLP. Staining of histological sections demonstrated that myocardial damage and cardiomyocyte apoptosis were alleviated by the administration of exogenous H 2 S. Western blot analysis was used to detect phosphorylated and total PI3K and Akt levels, as well as NF-κB, B-cell lymphoma-2, Bcl-2-associated X protein (Bax) and caspase levels, and the results demonstrated that H 2 S significantly increased PI3K and Akt phosphorylation. This indicated that the PI3K/Akt signaling pathway was activated by H 2 S. Additionally, H 2 S reduced Bax and caspase expression, indicating that apoptosis was inhibited, and decreased NF-κB levels, indicating that inflammation was reduced. Furthermore, the PI3K inhibitor LY294002 eliminated the protective effects of H 2 S. In conclusion, the results of the current study suggest that exogenous H 2 S activates PI3K/Akt signaling to attenuate myocardial damage in sepsis.

Exosomes from adipose tissue-derived mesenchymal stem cells ameliorate histone-induced acute lung injury by activating the PI3K/Akt pathway in endothelial cells

“…In many animal models of sepsis, endothelial cell damage is associated with apoptosis [19,40,41]. Additionally, improvement of the PI3K/Akt signaling pathway attenuated apoptosis and improved survival in animal models of sepsis [41][42][43]. ADSCs and exosomes have the potential to trigger the PI3K/Akt signaling pathway in wound healing [44] and myocardial ischemia/reperfusion injury [45].…”

Exosomes from Adipose Tissue-Derived Mesenchymal Stem Cells Ameliorate Histone-Induced Acute Lung Injury by Activating the PI3K/Akt Pathway in Endothelial Cells.

“…In many sepsis animal models, endothelial cell damage is associated with apoptosis [19,40,41]. Additionally, improvement of the PI3K/Akt signaling pathway attenuated apoptosis and improved survival in sepsis animal models [41][42][43]. ADSCs and exosomes have the potential to trigger the PI3K/Akt signaling pathway in wound healing [44] and myocardial ischemia/reperfusion injury [45].…”

L-Cysteine Provides Neuroprotection of Hypoxia-Ischemia Injury in Neonatal Mice via a PI3K/Akt-Dependent Mechanism

“… 9 Interestingly, the PI3K/Akt pathway contributes to HI-induced brain damage through suppressing microglial activation, neuroinflammation and neuronal apoptosis. 10 In addition, the protective effects of H 2 S treatment in myocardial 11 and cerebral ischemia were positively associated with this PI3K/Akt signaling pathway. 12 Based on these findings, we found that stimulation of Akt phosphorylation by L-Cysteine rescues brain function in neonatal mice exposed to HI insult.…”