| First Author | Hui Y | Year | 2024 |
| Journal | iScience | Volume | 27 |
| Issue | 1 | Pages | 108689 |
| PubMed ID | 38226157 | Mgi Jnum | J:351215 |
| Mgi Id | MGI:7575368 | Doi | 10.1016/j.isci.2023.108689 |
| Citation | Hui Y, et al. (2024) High glucose impairs cognitive function through inducing mitochondrial calcium overload in Treg cells. iScience 27(1):108689 |
| abstractText | High glucose has been proved to impair cognitive function in type 2 diabetes, but the underlying mechanisms remain elusive. Here, we found that high glucose increased transcription factors' SP1 O-GlcNAcylation in regulatory T (Treg) cells. Glycosylated SP1 further enhanced HDAC2 recruitment and histone deacetylation on Na(+)/Ca(2+)/Li(+) exchanger (NCLX) promoter, which downregulated NCLX expression and led to mitochondrial calcium overload and oxidative damage, thereby promoting Treg cell dysfunction, M1 microglia polarization, and diabetes-associated cognitive impairment. Importantly, GLP-1 receptor agonist alleviated these deleterious effects via GLP-1-receptor-mediated upregulation of OGA and inhibition of SP1 O-GlcNAcylation in Treg cells. Our study highlighted a link between high-glucose-mediated SP1 O-GlcNAcylation and HDAC2/NCLX signaling in control of mitochondrial calcium concentrations in Treg cells. It also revealed a mechanism for linking Treg cell dysfunction and cognitive impairment in type 2 diabetes and provides an insight into the mechanism underlying the neuroprotective effects of GLP-1 receptor agonist. |
