Aug 2026· Turkish Journal of Biochemistry· 0 citations· 59 references
TL;DR
The findings indicate that an increase in oxidative stress parameters arose at the earlier phase of ischemic neurodegenerative processes, while SREBP-1 expression increased in the mid-phase.
Abstract
Abstract Objectives Ischemic brain injury causes neurodegeneration. This study investigated the mechanism of neurodegeneration by examining the expression of transcription factors, sterol regulatory element-binding protein-1 (SREBP-1) and CCAAT enhancer-binding protein β (C/EBPβ), in a time course. Besides oxidative stress markers such as thiobarbituric acid-reactive substances (TBARS), total thiol molecule (TTM) levels, and superoxide dismutase (SOD), glutathione-S-transferase (GST) activities were also detected. Methods In adult male rats, carotid artery occlusion and hypotension were produced for 10 min. Control groups were sham-operated. Animals were sacrificed after 24 h, 1, 2, and 4 weeks of reperfusion periods. The expression of SREBP-1 and C/EBPβ in the rat brain cortex and cerebellum was examined by Western blotting. Results C/EBPβ expression significantly increased in both cytosolic (1.19-, 1.58-fold) and nuclear (1.73-, 1.81-fold) extracts of the brain cortex after 24 h and 1 week of reperfusion. In the cerebellum, C/EBPβ expression significantly increased in 1 week, cytosolic (1.63-fold), and nuclear (1.35-fold) extracts. SREBP-1 expression significantly increased in both cytosolic (2.07-fold) and nuclear (1.41-fold) extracts of the brain cortex after 1 week of reperfusion. SREBP-1 expression significantly increased in cytosolic (2.15-fold) and nuclear (1.79-fold) extracts of cerebellum after 1 week of reperfusion. In addition, TBARS levels and SOD activities significantly increased by 43.16 % and 47.30 %, respectively, after 24 h of reperfusion. Conclusions Our findings indicate that an increase in oxidative stress parameters arose at the earlier phase of ischemic neurodegenerative processes, while SREBP-1 expression increased in the mid-phase. C/EBPβ expressions were increased at early to mid-phases of reperfusion injury.
Ischemic stroke is a prevalent cerebrovascular disease and remains a major cause of chronic disability and death worldwide. Runt-related transcription factor-1 (RUNX1) is a critical member of the core-binding factor family abnormally elevated in ischemic brain tissue. However, the exact roles of RUNX1 and its underlying cellular mechanisms in cerebral ischemia/reperfusion (I/R) injury have not been explored. Here we found that RUNX1 was highly expressed in brain tissues from middle cerebral artery occlusion (MCAO) mice and oxygen-glucose deprivation and reperfusion (OGD/R)-treated HT22 cells. In vivo experiments also showed that knockdown of RUNX1 significantly reduced the infarct volume and ameliorated neurological deficits in MCAO mice. Next, we investigated the exact mechanisms underlying the neuroprotective effect of si-RUNX1 against cerebral I/R injury. The results showed that knockdown of RUNX1 suppressed endoplasmic reticulum stress (ERS) and ERS-mediated neuroinflammation, as well as ferritinophagy and ferroptosis in both MCAO mice and OGD/R-treated HT22 cells. Mechanistically, RUNX1 directly targeted ELAV-like family protein 2 (CELF2) and regulated its transcription, therefore regulating the mTOR signaling. We also found that CELF2/mTOR mediated the inhibitory effects of si-RUNX1 on ERS-mediated inflammation and ferritinophagy-mediated ferroptosis both in vivo and in vitro. In summary, these data taken together revealed that si-RUNX1 suppressed ERS-mediated neuroinflammation and ferritinophagy-mediated ferroptosis through regulating the CELF2/mTOR signaling. These findings indicated that RUNX1/CELF2/mTOR might serve as therapeutic targets for cerebral I/R injury.
Functional experiments revealed that silencing miR-9–5p protected against cerebral ischemia/reperfusion injury and suppressed NLRP3 inflammasome activation following IS, suggesting that its blockade could be a potential therapeutic strategy for ischemic brain injury.
APS effectively mitigated neuronal damage and motor dysfunction after cerebral ischemia and improved neurological function and ameliorated neuronal damage in rats subjected to middle cerebral artery occlusion.
Qi Wu, Jinzhong Ni, Hui Teng et al.· Drug Research· 0 citations
A new machine-learning framework aims to improve the success rate of computational protein design while moving away from results that reproduce sequences found in nature.