Article Sidebar
Published:
Mar 17, 2021DOI:
10.4314/tjpr.v20i1.4Keywords:
Article Details
Submission of a manuscript to this journal is a representation that the manuscript has not been published previously and is not under consideration for publication elsewhere.
All authors named in each manuscript would be required to sign a form (to be supplied by the Editor) so that they may retain their copyright in the article but to assign to us (the Publishers) and its licensees in perpetuity, in all forms, formats and media (whether known or created in the future) to (i) publish, reproduce, distribute, display and store the contribution, (ii) translate the contribution into other languages, create adaptations, reprints, include within collections and create summaries, extracts and/or abstracts of the contribution, (iii) create any other derivative works(s) based on the contribution, (iv) to exploit all subsidiary rights in the contribution, (v) the inclusion of electronic links from the contribution to third party material where-ever it may be located, and (vi) license any thrid party to do any or all of the above.
Main Article Content
Downregulation of FOXO4 promotes neuronal survival by mediating oxidative-stress–induced apoptosis after cerebral ischemia/reperfusion injury
Abstract
Purpose: To investigate the effect of FOXO4 on cerebral ischemia/reperfusion (CIR) injury and the underlying mechanism.
Methods: An in vitro ischemia/reperfusion (IR) model was achieved using oxygen-glucose deprivation/reoxygenation (OGD/R). Expression of RNA and protein was determined using quantitative real time polymerase chain reaction (qRT-PCR) and western blotting, respectively. Cell viability and apoptosis were determined using MTT assay and flow cytometry, respectively. Commercial kits were used to measure lactate dehydrogenase (LDH), reactive oxygen species (ROS), chloramphenicol acetyltransferase (CAT), malondialdehyde (MDA), and superoxide dismutase (SOD).
Results: Following OGD/R, FOXO4 mRNA and protein expressions were upregulated in SH-SY5H human neuroblastoma cells. ODG/R reduced cell proliferation and increased the proportion of apoptotic cells, and these effects were inhibited by knockdown of FOXO4 (p < 0.05). Levels of cleaved caspase 3 and cleaved poly(ADP-ribose) polymerases (PARPs) were increased after ODG/R and these increases
were inhibited by FOXO4 knockdown. ROS content and levels of LDH and MDA were increased after ODG/R and decreased by knockdown of FOXO4 (p < 0.05). Levels of CAT and SOD were reduced after ODG/R, and this reduction was reversed by knockdown of FOXO4 (p < 0.05).
Conclusion: The results demonstrate that knockdown of FOXO4 promotes cell proliferation and inhibits cellular apoptosis via reduction of oxidative stress after CIR injury, indicating a new therapeutic target for the treatment of CIR injury.
Keywords: FOXO4, Neuronal survival, Oxidative stress, Cerebral ischemia/reperfusion injury
