Vitamin B6 alleviates chronic sleep deprivation-induced hippocampal ferroptosis through CBS/GSH/GPX4 pathway - 27/04/24
Abstract |
Several studies have found that sleep deprivation (SD) can lead to neuronal ferroptosis and affect hippocampal function. However, there are currently no effective interventions. Vitamin B6 is a co-factor for key enzymes in the transsulfuration pathway which is critical for maintaining cell growth in the presence of cysteine deprivation. The results showed that SD inhibited cystine-glutamate antiporter light chain subunit xCT protein expression and caused cysteine deficiency, which reduced the synthesis of the glutathione (GSH) to trigger neuronal ferroptosis. Nissl staining further revealed significant neuronal loss and shrinkage in the CA1 and CA3 regions of the hippocampus in SD mice. Typical ferroptotic indicators characterized by lipid peroxidation and iron accumulation were showed in the hippocampus after sleep deprivation. As expected, vitamin B6 could alleviate hippocampal ferroptosis by upregulating the expression of cystathionine beta-synthase (CBS) in the transsulfuration pathway, thereby replenishing the intracellular deficient GSH and restoring the expression of GPX4. Similar anti-ferroptotic effects of vitamin B6 were demonstrated in HT-22 cells treated with ferroptosis activator erastin. Furthermore, vitamin B6 had no inhibitory effect on erastin-induced ferroptosis in CBS-knockout HT22 cells. Our findings suggested chronic sleep deprivation caused hippocampal ferroptosis by disrupting the cyst(e)ine/GSH/GPX4 axis. Vitamin B6 alleviated sleep deprivation-induced ferroptosis by enhancing CBS expression in the transsulfuration pathway.
Il testo completo di questo articolo è disponibile in PDF.Graphical Abstract |
Highlights |
● | Chronic sleep deprivation induces hippocampal ferroptosis by inhibiting xCT protein. |
● | Vitamin B6 alleviates lipid peroxidation and iron accumulation in vivo and in vitro. |
● | Vitamin B6 inhibits ferroptosis by enhancing CBS in the transsulfuration pathway. |
Keywords : Vitamin B6, Sleep deprivation, Ferroptosis, Cystathionine beta-synthase, Transsulfuration pathway
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Vol 174
Articolo 116547- Maggio 2024 Ritorno al numeroBenvenuto su EM|consulte, il riferimento dei professionisti della salute.
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