Propofol alleviates oxidative stress via upregulating lncRNA-TUG1/Brg1 pathway in hypoxia/reoxygenation hepatic cells

Abstract

Reducing oxidative stress is an effective method to prevent hepatic ischaemia/reperfusion injury (HIRI). This study focuses on the role of propofol on the oxidative stress of hepatic cells and the involved lncRNA-TUG1/Brahma-related gene 1 (Brg1) pathway in HIRI mice. The mouse HIRI model was established and was intraperitoneally injected with propofol postconditioning. Hepatic injury indexes were used to evaluate HIRI. The oxidative stress was indicated by increasing 8-isoprostane concentration. Mouse hepatic cell line AML12 was treated with hypoxia and subsequent reoxygenation (H/R). The targeted regulation of lncRNA-TUG1 on Brg1 was proved by RNA pull-down, RIP (RNA-binding protein immunoprecipitation) and the expression level of Brg1 responds to silencing or overexpression of lncRNA-TUG1. Propofol alleviates HIRI and induces the upregulation of lncRNA-TUG1 in the mouse HIRI model. Propofol increases cell viability and lncRNA-TUG1 expression level in H/R-treated hepatic cells. In H/R plus propofol-treated hepatic cells, lncRNA-TUG1 silencing reduces cell viability and increased oxidative stress. LncRNA-TUG1 interacts with Brg1 protein and keeps its level via inhibiting its degradation. Brg1 overexpression reverses lncRNA-TUG1 induced the reduction of cell viability and the increase in oxidative stress. LncRNA-TUG1 silencing abrogates the protective role of propofol against HIRI in the mouse HIRI model. LncRNA-TUG1 has a targeted regulation of Brg1, and thereby affects the oxidative stress induced by HIRI. This pathway mediates the protective effect of propofol against HIRI of hepatic cell.

Propofol protects cardiomyocytes from hypoxia/reoxygenation injury via regulating MALAT1/miR‐206/ATG3 axis

“…[27,35] Specifically, PPF alleviates oxidative stress by regulating the TUG1/Brg1 pathway in hepatocytes exposed to H/R. [36] PPF exhibits protective effects in I/R-induced liver injury by increasing miR-133a-5p expression and decreasing MAPK6 expression. [37] In this study, it was found that PPF could decrease the expression of MALAT1 and increase the expression of miR-206.…”

The Role of BRG1 in Antioxidant and Redox Signaling

“…BRG1-mediated Nrf2/HO-1 transcriptional activation is important for oxidative stress injury induced by ischemia/reperfusion (I/R) or hypoxia/reoxygenation (H/R). Propofol alleviates oxidative stress in anoxia/reoxygenated hepatocytes through the lncRNA-TUG1/BRG1 pathway [ 40 ]. Knockdown of BRG1 inhibited HO-1 expression, thereby weakening the protective effect of propofol postconditioning on hepatic ischemia/reperfusion injury (HIRI) [ 41 ].…”

Role of microRNA‑218‑5p in sevoflurane‑induced protective effects in hepatic ischemia/reperfusion injury mice by regulating GAB2/PI3K/AKT pathway

“…Excessive oxidative stress and excessive inflammatory response are well recognized as another contributory factor in the pathology of HIRI ( 30 ). Thus, the present study examined the protective effects of Sevo on oxidative stress.…”