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Heme oxygenase-1(HO-1) regulates Golgi stress and attenuates endotoxin-induced acute lung injury through hypoxia inducible factor-1? (HIF-1?)/HO-1 signaling pathway.

ABSTRACT: Sepsis caused acute lung injury (ALI) is a kind of serious disease in critically ill patients with very high morbidity and mortality. Recently, it has been demonstrated that Golgi is involved in the process of oxidative stress. However, whether Golgi stress is associated with oxidative stress in septic induced acute lung injury has not been elucidated. In this research, we found that lipopolysaccharide (LPS) induced oxidative stress, apoptosis, inflammation and Golgi morphology changes in acute lung injury both in vivo and in vitro. The knockout of heme oxygenase-1(HO-1) aggravated oxidative stress, inflammation, apoptosis and reduced the expression of Golgi matrix protein 130 (GM130), mannosidase ?, Golgi-associated protein golgin A1 (Golgin 97), and increased the expression of Golgi phosphoprotein 3 (GOLPH3), which caused the fragmentation of Golgi. Furtherly, the activation of hypoxia inducible factor-1? (HIF-1?)/HO-1 pathway, attenuates Golgi stress and oxidative stress by increasing the levels of GM130, mannosidase ?, Golgin 97, and decreasing the expression of GOLPH3 both in vivo and in vitro. Therefore, the activation of HO-1 plays a crucial role in alleviating sepsis-induced acute lung injury by regulating Golgi stress, oxidative stress, which may provide a therapeutic target for the treatment of acute lung injury.

SUBMITTER: Li X

PROVIDER: S-EPMC7825924 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Heme oxygenase-1(HO-1) regulates Golgi stress and attenuates endotoxin-induced acute lung injury through hypoxia inducible factor-1α (HIF-1α)/HO-1 signaling pathway.

Li Xiangyun X Yu Jianbo J Gong Lirong L Zhang Yuan Y Dong Shuan S Shi Jia J Li Cui C Li Yuting Y Zhang Yanfang Y Li Haibo H

Free radical biology & medicine 20210123

Sepsis caused acute lung injury (ALI) is a kind of serious disease in critically ill patients with very high morbidity and mortality. Recently, it has been demonstrated that Golgi is involved in the process of oxidative stress. However, whether Golgi stress is associated with oxidative stress in septic induced acute lung injury has not been elucidated. In this research, we found that lipopolysaccharide (LPS) induced oxidative stress, apoptosis, inflammation and Golgi morphology changes in acute ...[more]

PMID: 33493554

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Project description:Background/Aims: Diabetic foot ulcers (DFUs) present a major challenge in clinical practice, and hyperglycemia-induced angiogenesis disturbance and endothelial dysfunction likely exacerbate DFUs. The long-acting glucagon-like peptide-1 (GLP-1) analog liraglutide (Lira) is a potential activator of AMP-activated protein kinase (AMPK) that appears to enhance endothelial function and have substantial pro-angiogenesis and antioxidant stress effects. Therefore, in this study, we aimed to investigate whether the protective role of Lira in diabetic wound healing acts against the mechanisms underlying hyperglycemia-induced endothelial dysfunction and angiogenesis disturbance. Methods: Accordingly, db/db mice were assessed after receiving subcutaneous Lira injections. We also cultured human umbilical vein endothelial cells (HUVECs) in either normal or high glucose (5.5 or 33 mM glucose, respectively) medium with or without Lira for 72 h. Results: An obvious inhibition of hyperglycemia-triggered endothelial dysfunction and angiogenesis disturbance was observed; follow by a promotion of diabetic wound healing under Lira treatment combined with restored hyperglycemia-impaired AMPK signaling pathway activity. AMPKα1/2 siRNA and Compound C (Cpd C), an inhibitor of AMPK, abolished both Lira-mediated endothelial protection and pro-angiogenesis action, as well as the diabetic wound healing promoted by Lira. Furthermore, hypoxia inducible factor-1α (Hif-1α; transcription factors of AMPK substrates) knockdown in HUVECs and db/db mice demonstrated that Lira activated AMPK to prevent hyperglycemia-triggered endothelial dysfunction and angiogenesis disturbance, with a subsequent promotion of diabetic wound healing that was Hif-1α-heme oxygenase-1 (HO-1) axis-dependent. Taken together, these findings reveal that the promotion of diabetic wound healing by Lira occurs via its AMPK-dependent endothelial protection and pro-angiogenic effects, which are regulated by the Hif-1α-HO-1 axis.

Dataset Information

Heme oxygenase-1(HO-1) regulates Golgi stress and attenuates endotoxin-induced acute lung injury through hypoxia inducible factor-1? (HIF-1?)/HO-1 signaling pathway.

Publications

Heme oxygenase-1(HO-1) regulates Golgi stress and attenuates endotoxin-induced acute lung injury through hypoxia inducible factor-1α (HIF-1α)/HO-1 signaling pathway.

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