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High glucose and palmitic acid induces neuronal senescence by NRSF/REST elevation and the subsequent mTOR-related autophagy suppression.
- Source :
-
Molecular brain [Mol Brain] 2022 Jul 18; Vol. 15 (1), pp. 61. Date of Electronic Publication: 2022 Jul 18. - Publication Year :
- 2022
-
Abstract
- Cell senescence is a basic aging mechanism. Previous studies have found that the cellular senescence in adipose tissue and other tissues, such as the pancreas, muscle and liver, is associated with the pathogenesis and progression of type 2 diabetes; however, strong evidence of whether diabetes directly causes neuronal senescence in the brain is still lacking. In this study, we constructed a high glucose and palmitic acid (HGP) environment on PC12 neuronal cells and primary mouse cortical neurons to simulate diabetes. Our results showed that after HGP exposure, neurons exhibited obvious senescence-like phenotypes, including increased NRSF/REST level, mTOR activation and cell autophagy suppression. Downregulation of NRSF/REST could remarkably alleviate p16, p21 and γH2A.X upregulations induced by HGP treatment, and enhance mTOR-autophagy of neurons. Our results suggested that the diabetic condition could directly induce neuronal senescence, which is mediated by the upregulation of NRSF/REST and subsequent reduction of mTOR-autophagy.<br /> (© 2022. The Author(s).)
- Subjects :
- Animals
Autophagy
Glucose metabolism
Glucose pharmacology
Mice
Neurons metabolism
TOR Serine-Threonine Kinases metabolism
Diabetes Mellitus, Type 2 metabolism
Diabetes Mellitus, Type 2 pathology
Membrane Proteins metabolism
Palmitic Acid metabolism
Palmitic Acid pharmacology
Repressor Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1756-6606
- Volume :
- 15
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular brain
- Publication Type :
- Academic Journal
- Accession number :
- 35850767
- Full Text :
- https://doi.org/10.1186/s13041-022-00947-2