Regenerative therapy · 2025
Sevoflurane suppresses LPS-induced microglia injury by regulating USP11-mediated UHRF1 deubiquitination.
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Liu Dongzhi, Sun Chengliang, Zhang Xiuli, Gao Shunheng
Аннотация
BACKGROUND: Spinal cord injury (SCI) is a devastating neurological and pathological condition that leads to severe motor, sensory, and autonomic dysfunctions. The neuroprotective effect of Sevoflurane (Sevo) in the rat model of SCI has been reported. However, the mechanism of Sevo is still elusive.
METHODS: 24 rats were divided into four groups: sham group, sham + Sevo group, SCI group, and SCI + Sevo group. On days 0, 14, 28, and 42 post-SCI, functional recovery was evaluated using the BBB test. The histological changes in the spinal cord were observed by HE staining. Western blotting, ELISA, and corresponding kits were used to detect the effects of Sevo on apoptosis, inflammatory factors, and oxidative stress. Human microglia HMC3 were induced by lipopolysaccharide (LPS) to mimic the in vitro environment of SCI. Ubiquitin-specific peptidase 11 (USP11) and ubiquitin-like, containing PHD and RING finger domains 1 (UHRF1), B-cell lymphoma-2 (BCL-2), and Bcl-2 related X protein (BAX) protein levels were determined using Western blot. Cell apoptosis, Interleukin-1β (IL-1β), and IL-6 levels were assessed using flow cytometry and ELISA. malondialdehyde (MDA), glutathione (GSH), and Reactive oxygen species (ROS) products were examined using special assay kits. After Ubibrowser prediction, GO enrichment, and protein-protein interaction (PPI) networks, the interaction between USP11 and UHRF1 was verified using Co-immunoprecipitation (CoIP) assay.
RESULTS: Sevo treatment improved spinal cord functional recovery in rats, as evidenced by enhanced BBB locomotor rating scale and neuron death in vivo. Meanwhile, Sevo also reduced inflammation and oxidative damage in rats following SCI. Sevo exposure decreased USP11 and UHRF1 expression in LPS-treated HMC3 cells. Sevo repressed LPS-triggered HMC3 cell apoptosis, inflammatory response, and oxidative stress promotion by regulating USP11. At the molecular level, USP11 interacted with UHRF1 and maintained its stabilization by removing ubiquitin.
CONCLUSION: Sevo could protect LPS-induced HMC3 cell apoptosis, inflammation, and oxidative stress by regulating the USP11/UHRF1 axis, which might provide a novel therapeutic mechanism for Sevo in SCI.
METHODS: 24 rats were divided into four groups: sham group, sham + Sevo group, SCI group, and SCI + Sevo group. On days 0, 14, 28, and 42 post-SCI, functional recovery was evaluated using the BBB test. The histological changes in the spinal cord were observed by HE staining. Western blotting, ELISA, and corresponding kits were used to detect the effects of Sevo on apoptosis, inflammatory factors, and oxidative stress. Human microglia HMC3 were induced by lipopolysaccharide (LPS) to mimic the in vitro environment of SCI. Ubiquitin-specific peptidase 11 (USP11) and ubiquitin-like, containing PHD and RING finger domains 1 (UHRF1), B-cell lymphoma-2 (BCL-2), and Bcl-2 related X protein (BAX) protein levels were determined using Western blot. Cell apoptosis, Interleukin-1β (IL-1β), and IL-6 levels were assessed using flow cytometry and ELISA. malondialdehyde (MDA), glutathione (GSH), and Reactive oxygen species (ROS) products were examined using special assay kits. After Ubibrowser prediction, GO enrichment, and protein-protein interaction (PPI) networks, the interaction between USP11 and UHRF1 was verified using Co-immunoprecipitation (CoIP) assay.
RESULTS: Sevo treatment improved spinal cord functional recovery in rats, as evidenced by enhanced BBB locomotor rating scale and neuron death in vivo. Meanwhile, Sevo also reduced inflammation and oxidative damage in rats following SCI. Sevo exposure decreased USP11 and UHRF1 expression in LPS-treated HMC3 cells. Sevo repressed LPS-triggered HMC3 cell apoptosis, inflammatory response, and oxidative stress promotion by regulating USP11. At the molecular level, USP11 interacted with UHRF1 and maintained its stabilization by removing ubiquitin.
CONCLUSION: Sevo could protect LPS-induced HMC3 cell apoptosis, inflammation, and oxidative stress by regulating the USP11/UHRF1 axis, which might provide a novel therapeutic mechanism for Sevo in SCI.