Journal article
Gentamycin Rationally Repositioned to Inhibit miR-34a Ameliorates Oxidative Injury to PC12 Cells
ACS omega, Vol.8(1), pp.771-781
10/01/2023
PMID: 36643496
Metrics
1 Record Views
Abstract
Ischemic stroke accompanies oxidative stress and cell death in the cerebral tissue. The microRNA miR-34a plays a pivotal role in this molecular pathology. This study presents the rational repositioning of aminoglycosidic antibiotics as miR-34a antagonists in order to assess their efficiency in protecting the PC12 stroke model cells from oxidative stress occurring under cerebral ischemic conditions. A library of 29 amino-sugar compounds were screened against anticipated structural models of miR-34a through molecular docking. MiR-ligand interactions were mechanistically studied by molecular dynamics simulations and free-energy calculations. Cultured PC12 cells were treated by H2O2 alone or in combination with gentamycin and neomycin as selected drugs. Cell viability and apoptosis were detected by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) and annexin V-FITC/propidium iodate (PI) double staining assays, respectively. The expression levels of key factors involved in cell proliferation, oxidative stress, and apoptosis in treated PC12 cells were measured through a quantitative real-time polymerase chain reaction and flow cytometric annexin V-FITC/PI double staining assays. A stable and energetically favorable binding was observed for miR-34a with gentamycin and neomycin. Gentamycin pretreatments followed by H2O2 oxidative injury led to increased cell viability and protected PC12 cells against H2O2-induced apoptotic events. This study will help in further understanding how the suppression of miR-34a in neural tissue affects the cell viability upon stroke.
Details
- Title
- Gentamycin Rationally Repositioned to Inhibit miR-34a Ameliorates Oxidative Injury to PC12 Cells
- Creators
- Zhila Izadi - Kermanshah University of Medical SciencesEbrahim Barzegari - Kermanshah University of Medical SciencesAmin Iranpanah - Kermanshah University of Medical SciencesSoraya Sajadimajd - Razi UniversityHossein Derakhshankhah - Kermanshah University of Medical Sciences
- Publication Details
- ACS omega, Vol.8(1), pp.771-781
- Publisher
- American Chemical Society
- Number of pages
- 11
- Grant note
- This work was supported by the National Institute for Medical Research Development of the Islamic Republic of Iran (NIMAD, grant number: 984499) and the Kermanshah University of Medical Sciences, Kermanshah, Iran.
- Identifiers
- 991013400558702368
- Copyright
- © 2022 The Authors.
- Academic Unit
- Faculty of Health
- Language
- English
- Resource Type
- Journal article