Helix B surface peptide protects against acute lung injury through reducing oxidative stress and endoplasmic reticulum stress via activation of Nrf2/HO-1 signaling pathway
X.-G. Bi, M.-L. Li, W. Xu, J.-Y. You, D. Xie, X.-F. Yuan, Y. Xiang Department of General ICU, The Third Affiliated Hospital of Sun Yat-sen University-Lingnan Hospital, Guangzhou, China. bxg655@sina.com
OBJECTIVE: Acute lung injury (ALI) is a clinical problem with poor prognosis and high mortality. The purpose of this study was to explore the effects of helix B position peptide (HBSP) on ALI and its mechanism.
MATERIALS AND METHODS: C57/BL6 male mice were used to construct ALI models by LPS tracheal injection and detect the effect of HBSP on mouse ALI by subcutaneously injecting HBSP. In addition, normal human lung epithelial cell line (BEAS-2B) were cultured and stimulated with HBSP. Then, the effects of HBSP on oxidative stress and endoplasmic reticulum stress (ERS) in BEAS-2B cells were examined. Finally, the effect of HBSP on the Nrf2/HO-1 signaling pathway was examined, and the mechanism of action of HBSP was verified using the Nrf2/HO-1 signaling pathway inhibitor ML385.
RESULTS: In vitro, HBSP increased the expression of SOD1/2 and decreased the expression of ERS-related molecules such as CHOP, GRP-78, and caspase-12, indicating that HBSP effectively reduces the level of oxidative stress and ERS in BEAS-2B cells. In addition, HBSP also increased the activity of the Nrf2/HO-1 signaling pathway and ML385 reduced the protective effect of HBSP on BEAS-2B cells. In vivo, HBSP significantly reduced LPS-induced mouse ALI. W/D and inflammatory factors in the BALF of the mouse lung were significantly reduced and the level of oxidative stress was also reduced.
CONCLUSIONS: HBSP plays an important role in relieving ALI by activating Nrf2/HO-1 signaling pathway, which reduces the level of inflammation in lung tissue and oxidative stress and ERS in lung epithelial cells.
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X.-G. Bi, M.-L. Li, W. Xu, J.-Y. You, D. Xie, X.-F. Yuan, Y. Xiang
Helix B surface peptide protects against acute lung injury through reducing oxidative stress and endoplasmic reticulum stress via activation of Nrf2/HO-1 signaling pathway
Eur Rev Med Pharmacol Sci
Year: 2020
Vol. 24 - N. 12
Pages: 6919-6930
DOI: 10.26355/eurrev_202006_21683