Phosphatidylinositol 3‑kinase‑mediated HO‑1/CO represses Fis1 levels and alleviates lipopolysaccharide‑induced oxidative injury in alveolar macrophages

  • Authors:
    • Jia Shi
    • Jianbo Yu
    • Yuan Zhang
    • Zhen Li
    • Lirong Gong
    • Shuan Dong
    • Rui Mu
  • View Affiliations

  • Published online on: July 17, 2018     https://doi.org/10.3892/etm.2018.6448
  • Pages: 2735-2742
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Abstract

Sepsis‑related acute respiratory distress syndrome is characterized by marked oxidative stress and mitochondrial dysfunction lacking of specific therapy. Heme oxygenase (HO)‑1 followed by endogenous carbon monoxide (CO) exerted a cytoprotective effect against multi‑organ damage during sepsis. Additionally, the phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (Akt) pathway, which serves as an upstream regulator of HO‑1, was associated with inflammation and oxidative stress. Therefore, the purpose of the present study was to investigate whether the PI3K/Akt pathway was involved in the effects of HO‑1/CO on the expression of mitochondrial fission 1 protein (Fis1). In the present study, CO releasing molecule‑2 (CORM2), as the exogenous source of CO, plus LY294002, as a specific PI3K inhibitor, were pre‑incubated in lipopolysaccharide (LPS)‑simulated rat NR8383 alveolar macrophages. The results demonstrated that CORM2 improved cell viability, inhibited tumor necrosis factor‑α levels, malondialdehyde contents, while elevating interleukin‑10 levels and superoxide dismutase activities. In addition, pretreatment with CORM2 suppressed the fragmentation of mitochondria, upregulated the expressions of phosphorylated‑Akt and HO‑1 but downregulated the levels of Fis1 mRNA and protein in LPS‑exposed cells. However, pretreatment with LY294002 significantly inhibited the phosphorylation of Akt, decreased HO‑1 levels, aggravated mitochondrial fragmentation, increased Fis1 mRNA and protein levels, and reversed the above protective effects of CORM2. Collectively, the results of the present study indicated that the PI3K/Akt pathway mediated the cytoprotective effects of HO‑1/CO on the transcription and translational levels of Fis1, and alleviated LPS‑induced oxidative injury in alveolar macrophages.
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September-2018
Volume 16 Issue 3

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Shi J, Yu J, Zhang Y, Li Z, Gong L, Dong S and Mu R: Phosphatidylinositol 3‑kinase‑mediated HO‑1/CO represses Fis1 levels and alleviates lipopolysaccharide‑induced oxidative injury in alveolar macrophages. Exp Ther Med 16: 2735-2742, 2018.
APA
Shi, J., Yu, J., Zhang, Y., Li, Z., Gong, L., Dong, S., & Mu, R. (2018). Phosphatidylinositol 3‑kinase‑mediated HO‑1/CO represses Fis1 levels and alleviates lipopolysaccharide‑induced oxidative injury in alveolar macrophages. Experimental and Therapeutic Medicine, 16, 2735-2742. https://doi.org/10.3892/etm.2018.6448
MLA
Shi, J., Yu, J., Zhang, Y., Li, Z., Gong, L., Dong, S., Mu, R."Phosphatidylinositol 3‑kinase‑mediated HO‑1/CO represses Fis1 levels and alleviates lipopolysaccharide‑induced oxidative injury in alveolar macrophages". Experimental and Therapeutic Medicine 16.3 (2018): 2735-2742.
Chicago
Shi, J., Yu, J., Zhang, Y., Li, Z., Gong, L., Dong, S., Mu, R."Phosphatidylinositol 3‑kinase‑mediated HO‑1/CO represses Fis1 levels and alleviates lipopolysaccharide‑induced oxidative injury in alveolar macrophages". Experimental and Therapeutic Medicine 16, no. 3 (2018): 2735-2742. https://doi.org/10.3892/etm.2018.6448