Modulation of Mitochondrial Metabolic Parameters and Antioxidant Enzymes in Healthy and Glaucomatous Trabecular Meshwork Cells with Hybrid Small Molecule SA-2

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dc.creatorAmankwa, Charles E.
dc.creatorYoung, Olivia
dc.creatorDebNath, Biddut
dc.creatorGondi, Sudershan R.
dc.creatorRangan, Rajiv
dc.creatorEllis, Dorette Z.
dc.creatorZode, Gulab S.
dc.creatorStankowska, Dorota L.
dc.creatorAcharya, Suchismita
dc.creator.orcid0000-0001-5098-5555 (Acharya, Suchismita)
dc.creator.orcid0000-0002-7823-2595 (Zode, Gulab S.)
dc.date.accessioned2023-08-03T20:08:26Z
dc.date.available2023-08-03T20:08:26Z
dc.date.issued2023-07-29
dc.description.abstractOxidative stress (OS)-induced mitochondrial damage is a risk factor for primary open-angle glaucoma (POAG). Mitochondria-targeted novel antioxidant therapies could unearth promising drug candidates for the management of POAG. Previously, our dual-acting hybrid molecule SA-2 with nitric oxide-donating and antioxidant activity reduced intraocular pressure and improved aqueous humor outflow in rodent eyes. Here, we examined the mechanistic role of SA-2 in trabecular meshwork (TM) cells in vitro and measured the activity of intracellular antioxidant enzymes during OS. Primary human TM cells isolated from normal (hNTM) or glaucomatous (hGTM) post-mortem donors and transformed glaucomatous TM cells (GTM-3) were used for in vitro assays. We examined the effect of SA-2 on oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) in vitro using Seahorse Analyzer with or without the oxidant, tert-butyl hydroperoxide (TBHP) treatment. Concentrations of total antioxidant enzymes, catalase (CAT), malondialdehyde (MDA), and glutathione peroxidase (GPx) were measured. We observed significant protection of both hNTM and hGTM cells from TBHP-induced cell death by SA-2. Antioxidant enzymes were elevated in SA-2-treated cells compared to TBHP-treated cells. In addition, SA-2 demonstrated an increase in mitochondrial metabolic parameters. Altogether, SA-2 protected both normal and glaucomatous TM cells from OS via increasing mitochondrial energy parameters and the activity of antioxidant enzymes.
dc.description.sponsorshipThis research was funded by the National Institute of Health, grant number R01EY029823.
dc.identifier.citationAmankwa, C. E., Young, O., DebNath, B., Gondi, S. R., Rangan, R., Ellis, D. Z., Zode, G., Stankowska, D. L., & Acharya, S. (2023). Modulation of Mitochondrial Metabolic Parameters and Antioxidant Enzymes in Healthy and Glaucomatous Trabecular Meshwork Cells with Hybrid Small Molecule SA-2. International journal of molecular sciences, 24(14), 11557. https://doi.org/10.3390/ijms241411557
dc.identifier.issn1422-0067
dc.identifier.issue14
dc.identifier.urihttps://hdl.handle.net/20.500.12503/32381
dc.identifier.volume24
dc.publisherMDPI
dc.relation.urihttps://doi.org/10.3390/ijms241411557
dc.rights.holder© 2023 by the authors.
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceInternational Journal of Molecular Sciences
dc.subjectantioxidants
dc.subjectextracellular acidification rate
dc.subjectmitochondria
dc.subjectoxygen consumption rate
dc.subjectsmall molecules
dc.subjecttrabecular meshwork
dc.subject.meshHumans
dc.subject.meshAntioxidants / metabolism
dc.subject.meshTrabecular Meshwork / metabolism
dc.subject.meshGlaucoma, Open-Angle / drug therapy
dc.subject.meshGlaucoma, Open-Angle / metabolism
dc.subject.meshGlaucoma / drug therapy
dc.subject.meshGlaucoma / metabolism
dc.subject.meshMitochondria / metabolism
dc.titleModulation of Mitochondrial Metabolic Parameters and Antioxidant Enzymes in Healthy and Glaucomatous Trabecular Meshwork Cells with Hybrid Small Molecule SA-2
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