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Chen 2020 Chem Biol Interact

From Bioblast
Publications in the MiPMap
Chen HY, Ho YJ, Chou HC, Liao EC, Tsai YT, Wei YS, Lin LH, Lin MW, Wang YS, Ko ML, Chan H (2020) TGF-β1 signaling protects retinal ganglion cells from oxidative stress via modulation of the HO-1/Nrf2 pathway. Chem Biol Interact 331:109249.

» PMID: 32980322

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 β (TGF-β) has appeared as a neuroprotective protein in various indignities. However, the TGF-β 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-β1 & TGF-β2 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-β1 & TGF-β2 was upregulated in RGCs after H2O2 stimulation. Cell functional assays resulted that knockdown of TGF-β1 & TGF-β2 reduced survival rate whereas enhanced apoptosis and accumulation of reactive oxygen species (ROS). Especially TGF-β1 upregulation promoted the protein expression of aldehyde dehydrogenase 3A1 (ALDH3A1) and increased the activity of antioxidant and neuroprotection pathways. Additionally, TGF-β1 & TGF-β2 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-1α) caused mitochondrial damage and led to neurodegeneration. In summary, our results demonstrated that TGF-β1 preserves RGCs from free radicals-mediated injury by upregulating the activation of Nrf2 expression and HO-1 signaling balance HIF-1α upregulation, implying a prospective role of TGF-β1 in retinal neuroprotection-related therapies. Keywords: HO-1/Nrf2 pathway, Oxidative stress, Retinal ganglion cells, TGF-β1 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