Chen 2020 Chem Biol Interact: Difference between revisions

Revision as of 21:43, 1 October 2020

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 [Epub ahead of print].

» 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

2020-10

@@ Line 2: / Line 2: @@
 |title=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 [Epub ahead of print].
 |info=[https://www.ncbi.nlm.nih.gov/pubmed/32980322 PMID: 32980322]
-|authors=Chen HY, Ho YJ, Chou HC, Liao EC, Tsai YT, Wei YS, Lin LH, Lin MW, Wang YS, Ko ML, Chan H
+|authors=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
 |year=2020
 |journal=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 (H<sub>2</sub>O<sub>2</sub>)-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 H<sub>2</sub>O<sub>2</sub> 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.
+|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 (H<sub>2</sub>O<sub>2</sub>)-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 H<sub>2</sub>O<sub>2</sub> 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
 |editor=[[Plangger M]]
@@ Line 11: / Line 11: @@
 {{Labeling
 |area=Respiration
+|injuries=Oxidative stress;RONS
+|organism=Mouse
+|tissues=Nervous system
+|preparations=Intact cells
+|couplingstates=LEAK, ROUTINE, ET
+|pathways=ROX
 |instruments=Oxygraph-2k
 |additional=2020-10
 }}