Rosiglitazone Ameliorates Spinal Cord Injury via Inhibiting Mitophagy and Inflammation of Neural Stem Cells.
Oxid Med Cell Longev
; 2022: 5583512, 2022.
Article
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| MEDLINE
| ID: mdl-35028008
ABSTRACT
BACKGROUND:
Neurodegenerative diseases, such as Alzheimer's disease, and traumatic brain and spinal cord injury (SCI) are prevalent in clinical practice. Inhibition of hyperactive inflammation and proliferation of endogenous neural stem cells (NSCs) is a promising treatment strategy for SCI. Our previous studies demonstrated the beneficial effects of rosiglitazone (Rosi) on SCI, but its roles in inflammation inhibition and proliferation of NSCs are unknown.METHODS:
SCI in a rat model was established, and the effects of Rosi on motor functions were assessed. The effects of Rosi on NSC proliferation and the underlying mechanisms were explored in details.RESULTS:
We showed that Rosi ameliorated impairment of moto functions in SCI rats, inhibited inflammation, and promoted proliferation of NSCs in vivo. Rosi increased ATP production through enhancing glycolysis but not oxidative phosphorylation. Rosi reduced mitophagy by downregulating PTEN-induced putative kinase 1 (PINK1) transcription to promote NSC proliferation, which was effectively reversed by an overexpression of PINK1 in vitro. Through KEGG analysis and experimental validations, we discovered that Rosi reduced the expression of forkhead box protein O1 (FOXO1) which was a critical transcription factor of PINK1. Three FOXO1 consensus sequences (FCSs) were found in the first intron of the PINK1 gene, which could be potentially binding to FOXO1. The proximal FCS (chr 5 156680169-156680185) from the translation start site exerted a more significant influence on PINK1 transcription than the other two FCSs. The overexpression of FOXO1 entirely relieved the inhibition of PINK1 transcription in the presence of Rosi.CONCLUSIONS:
Besides inflammation inhibition, Rosi suppressed mitophagy by reducing FOXO1 to decrease the transcription of PINK1, which played a pivotal role in accelerating the NSC proliferation.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Traumatismos de la Médula Espinal
/
Células-Madre Neurales
/
Mitofagia
/
Rosiglitazona
/
Hipoglucemiantes
/
Inflamación
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Oxid Med Cell Longev
Asunto de la revista:
METABOLISMO
Año:
2022
Tipo del documento:
Article