Review of the article The GPCR Antagonistic Drug CM-20 Stimulates Mitochondrial Activity in Human RPE Cells
Article (Accepted Version)
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Abstract:
Background:
Age-related macular degeneration (AMD) is the leading cause of low vision and vision loss in the elderly population. Mitochondrial dysfunction deteriorating bioenergetics in retinal pigment epithelial (RPE) cells is etiologically associated with the onset and progression of AMD. Improvement of mitochondrial function may have therapeutic potential to protect RPE cells from degenerative loss.
Objective:
Test the mitochondrial targeting activity of FDA-approved G-protein coupled receptor (GPCR) antagonist (CM-20), a neuroprotective lead compound we previously identified, in RPE cells.
Methods:
Human-derived RPE cell line (ARPE-19) was differentiated to improve RPE morphology and related function. Dose response experiments were performed in differentiated ARPE-19 (dRPE) cells to test the bioactivity of CM-20 on mitochondrial membrane potential (MMP), denoting mitochondrial activity. Secondary assays with multiplexed live-cell mit...ochondrial imaging were applied for additional evaluation of CM-20. Protection of CM-20 to mitochondria against the retina-generated endogenous oxidative stressor (hydrogen peroxide) was examined.
Results:
Treatment with CM-20 elicited a dose-dependent increase of MMP. Multiplexed live-cell mitochondrial imaging showed a consistent increase in MMP under treatment with CM-20 at an optimal concentration (12.5 µM). MMP was significantly decreased under oxidative stress, and pre-treatment with CM-20 showed a rescue effect to increase MMP.
Conclusion:
The GPCR antagonist (CM-20) exhibited novel bioactivity to stimulate mitochondrial activity, indicating a dual targeting drug to both GPCR and mitochondria. Since both GPCRs and mitochondria are considered as retinal drug targets, in vivo testing of CM-20 in retinal protection is warranted for poly pharmacological therapy.
Source:
The Open Biochemistry Journal, 2022, 1/BMS-TOBIOCI-2021-7-6Collections
Institution/Community
Mašinski fakultetTY - JOUR AU - Jovanović, Tamara PY - 2022 UR - https://machinery.mas.bg.ac.rs/handle/123456789/5786 AB - Abstract: Background: Age-related macular degeneration (AMD) is the leading cause of low vision and vision loss in the elderly population. Mitochondrial dysfunction deteriorating bioenergetics in retinal pigment epithelial (RPE) cells is etiologically associated with the onset and progression of AMD. Improvement of mitochondrial function may have therapeutic potential to protect RPE cells from degenerative loss. Objective: Test the mitochondrial targeting activity of FDA-approved G-protein coupled receptor (GPCR) antagonist (CM-20), a neuroprotective lead compound we previously identified, in RPE cells. Methods: Human-derived RPE cell line (ARPE-19) was differentiated to improve RPE morphology and related function. Dose response experiments were performed in differentiated ARPE-19 (dRPE) cells to test the bioactivity of CM-20 on mitochondrial membrane potential (MMP), denoting mitochondrial activity. Secondary assays with multiplexed live-cell mitochondrial imaging were applied for additional evaluation of CM-20. Protection of CM-20 to mitochondria against the retina-generated endogenous oxidative stressor (hydrogen peroxide) was examined. Results: Treatment with CM-20 elicited a dose-dependent increase of MMP. Multiplexed live-cell mitochondrial imaging showed a consistent increase in MMP under treatment with CM-20 at an optimal concentration (12.5 µM). MMP was significantly decreased under oxidative stress, and pre-treatment with CM-20 showed a rescue effect to increase MMP. Conclusion: The GPCR antagonist (CM-20) exhibited novel bioactivity to stimulate mitochondrial activity, indicating a dual targeting drug to both GPCR and mitochondria. Since both GPCRs and mitochondria are considered as retinal drug targets, in vivo testing of CM-20 in retinal protection is warranted for poly pharmacological therapy. T2 - The Open Biochemistry Journal T1 - Review of the article The GPCR Antagonistic Drug CM-20 Stimulates Mitochondrial Activity in Human RPE Cells EP - 6 SP - 1/BMS-TOBIOCI-2021-7 UR - https://hdl.handle.net/21.15107/rcub_machinery_5786 ER -
@article{ author = "Jovanović, Tamara", year = "2022", abstract = "Abstract: Background: Age-related macular degeneration (AMD) is the leading cause of low vision and vision loss in the elderly population. Mitochondrial dysfunction deteriorating bioenergetics in retinal pigment epithelial (RPE) cells is etiologically associated with the onset and progression of AMD. Improvement of mitochondrial function may have therapeutic potential to protect RPE cells from degenerative loss. Objective: Test the mitochondrial targeting activity of FDA-approved G-protein coupled receptor (GPCR) antagonist (CM-20), a neuroprotective lead compound we previously identified, in RPE cells. Methods: Human-derived RPE cell line (ARPE-19) was differentiated to improve RPE morphology and related function. Dose response experiments were performed in differentiated ARPE-19 (dRPE) cells to test the bioactivity of CM-20 on mitochondrial membrane potential (MMP), denoting mitochondrial activity. Secondary assays with multiplexed live-cell mitochondrial imaging were applied for additional evaluation of CM-20. Protection of CM-20 to mitochondria against the retina-generated endogenous oxidative stressor (hydrogen peroxide) was examined. Results: Treatment with CM-20 elicited a dose-dependent increase of MMP. Multiplexed live-cell mitochondrial imaging showed a consistent increase in MMP under treatment with CM-20 at an optimal concentration (12.5 µM). MMP was significantly decreased under oxidative stress, and pre-treatment with CM-20 showed a rescue effect to increase MMP. Conclusion: The GPCR antagonist (CM-20) exhibited novel bioactivity to stimulate mitochondrial activity, indicating a dual targeting drug to both GPCR and mitochondria. Since both GPCRs and mitochondria are considered as retinal drug targets, in vivo testing of CM-20 in retinal protection is warranted for poly pharmacological therapy.", journal = "The Open Biochemistry Journal", title = "Review of the article The GPCR Antagonistic Drug CM-20 Stimulates Mitochondrial Activity in Human RPE Cells", pages = "6-1/BMS-TOBIOCI-2021-7", url = "https://hdl.handle.net/21.15107/rcub_machinery_5786" }
Jovanović, T.. (2022). Review of the article The GPCR Antagonistic Drug CM-20 Stimulates Mitochondrial Activity in Human RPE Cells. in The Open Biochemistry Journal, 1/BMS-TOBIOCI-2021-7-6. https://hdl.handle.net/21.15107/rcub_machinery_5786
Jovanović T. Review of the article The GPCR Antagonistic Drug CM-20 Stimulates Mitochondrial Activity in Human RPE Cells. in The Open Biochemistry Journal. 2022;:1/BMS-TOBIOCI-2021-7-6. https://hdl.handle.net/21.15107/rcub_machinery_5786 .
Jovanović, Tamara, "Review of the article The GPCR Antagonistic Drug CM-20 Stimulates Mitochondrial Activity in Human RPE Cells" in The Open Biochemistry Journal (2022):1/BMS-TOBIOCI-2021-7-6, https://hdl.handle.net/21.15107/rcub_machinery_5786 .