Chen 2020 Chem Biol Interact
| Chen HY, Ho YJ, Chou HC, Liao EC, Tsai YT, Wei YS, Lin LH, Lin MW, Wang YS, Ko ML, Chan H (2020) TGF-Ξ²1 signaling protects retinal ganglion cells from oxidative stress via modulation of the HO-1/Nrf2 pathway. Chem Biol Interact [Epub ahead of print]. |
Chen Hsin-Yi, Ho Yi-Jung, Chou Hsiu-Chuan, Liao En-Chi, Tsai Yi-Ting, Wei Yu-Shan, Lin Li-Hsun, Lin Meng-Wei, Wang Yi-Shiuan, Ko Mei-Lan, Chan Hong-Lin (2020) Chem Biol Interact
Abstract: Oxidative stress provides a major contribution to the pathogenesis of glaucoma and may induce retinal ganglion cell (RGC) damage. Transforming growth factor Ξ² (TGF-Ξ²) has appeared as a neuroprotective protein in various indignities. However, the TGF-Ξ² mechanism of protective effects against oxidative stress damage in RGCs still undetermined. In our research, we investigated the regulatory mechanisms and potential effects of TGF-Ξ²1 & TGF-Ξ²2 in hydrogen peroxide (H2O2)-stimulated oxidative stress of RGCs in vitro. By a series of cell functional qualitative analysis, such as MTT cell viability assay, wound healing ability assay, apoptosis assay, intracellular ROS detection, immunoblot analysis, intracellular GSH content, and high-resolution respirometry, we illustrated the cell state in oxidative stress-induced injury. Results of protein expression showed that TGF-Ξ²1 & TGF-Ξ²2 was upregulated in RGCs after H2O2 stimulation. Cell functional assays resulted that knockdown of TGF-Ξ²1 & TGF-Ξ²2 reduced survival rate whereas enhanced apoptosis and accumulation of reactive oxygen species (ROS). Especially TGF-Ξ²1 upregulation promoted the protein expression of aldehyde dehydrogenase 3A1 (ALDH3A1) and increased the activity of antioxidant and neuroprotection pathways. Additionally, TGF-Ξ²1 & TGF-Ξ²2 on antioxidant signaling was related to activation of heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor (Nrf2), which are stress-response proteins. ROS accumulation followed by the accumulation of hypoxia-inducible factor (HIF-1Ξ±) caused mitochondrial damage and led to neurodegeneration. In summary, our results demonstrated that TGF-Ξ²1 preserves RGCs from free radicals-mediated injury by upregulating the activation of Nrf2 expression and HO-1 signaling balance HIF-1Ξ± upregulation, implying a prospective role of TGF-Ξ²1 in retinal neuroprotection-related therapies. β’ Keywords: HO-1/Nrf2 pathway, Oxidative stress, Retinal ganglion cells, TGF-Ξ²1 β’ Bioblast editor: Plangger M
Labels: MiParea: Respiration
Stress:Oxidative stress;RONS Organism: Mouse Tissue;cell: Nervous system Preparation: Intact cells
Coupling state: LEAK, ROUTINE, ET
Pathway: ROX
HRR: Oxygraph-2k
2020-10
