Tetramethylpyrazine protects retinal ganglion cells against H2O2‑induced damage via the�microRNA‑182/mitochondrial pathway

Abstract

Glaucoma is the leading cause of irreversible blindness worldwide; the apoptosis of the retinal ganglion cells (RGCs) is a hallmark of glaucoma. Tetramethylpyrazine (TMP) is the main active component of Ligusticum wallichii Franchat , and has been demonstrated to improve a variety of injuries through its antioxidative and antiapoptotic properties. However, these effects of TMP on glaucoma have not been studied. The present study aimed to investigate the potential role of TMP in glaucoma and to elucidate its possible mechanisms responsible for these effects. An in vitro model was generated, in which primary RGCs (PRGCs) were treated with H 2 O 2 . Our study revealed that TMP protected against H 2 O 2- induced injury to PRGCs, as evidenced by enhanced cell viability, reduced caspase 3 activity and decreased cell apoptosis. We also reported that TMP treatment inhibited reactive oxygen species (ROS) production and malondialdehyde levels, but upregulated the antioxidative enzyme superoxide dismutase. In particular, TMP significantly increased the expression of microRNA-182-5p (miR-182) in H 2 O 2 -treated PRGCs, which was selected as the target miRNA for further research. In addition, our findings suggested that the protective effects of TMP on H 2 O 2 -induced injury were attenuated by knockdown of miR-182. The results of a luciferase reporter assay demonstrated that Bcl-2 interacting protein 3 (BNIP3), an effector of mitochondria-mediated apoptosis, was a direct target of miR-182. In addition, TMP treatment significantly decreased the expression of BNIP3, Bax, cleaved-caspase-3 and cleaved-poly(ADP-ribose)polymerase, but increased that of Bcl-2. Also, TMP treatment decreased the release of cytochrome c from mitochondria and improved mitochondrial membrane potential in H 2 O 2 -treated RGCs. Of note, the inhibitory effects of TMP on the mitochondrial apoptotic pathway were suggested to be reversed by knockdown of miR-182. Collectively, our findings provide novel evidence that TMP protects PRGCs against H 2 O 2 -induced damage through suppressing apoptosis and oxidative stress via the miR-182/mitochondrial apoptotic pathway.

MicroRNA-182-5p protects human lens epithelial cells against oxidative stress-induced apoptosis by inhibiting NOX4 and p38 MAPK signalling

“…Another study demonstrated that the expression of miR-34a was up-regulated in HLE-B3 cells treated by H 2 O 2 [17]. In this study, we observed that expression of miR-182-5p was signi cantly downregulated by the treatment of H 2 O 2 in HLE-B3 cells, which was consistent with previous work [18].…”

MicroRNA-182-5p protects human lens epithelial cells against oxidative stress-induced apoptosis by inhibiting NOX4 and p38 MAPK signalling

“…Another study demonstrated that the expression of miR-34a was up-regulated in HLE-B3 cells treated by H 2 O 2 [17]. In this study, we observed that expression of miR-182-5p was significantly downregulated by the treatment of H 2 O 2 in HLE-B3 cells, which was consistent with previous work [18]. Emerging evidence suggests that miR-182-5p contributes to anti-apoptotic and anti-oxidative processes.…”

MicroRNA-182-5p protects human lens epithelial cells against oxidative stress-induced apoptosis by inhibit ing NOX4 and p38 MAPK signaling

“…Another study demonstrated that the expression of miR-34a was up-regulated in HLE-B3 cells treated by H 2 O 2 [16]. In this study, the expression of miR-182-5p were significantly downregulated by the treatment of H 2 O 2 in HLE-B3 cells, which was consistent with previous work [17]. Emerging evidence suggests that miR-182-5p contribute to anti-apoptotic and antioxidative processes.…”