A role for the cystathionine-β-synthase /H2S axis in astrocyte dysfunction in the aging brain

Autor: Anindya Dey, Pijush Kanti Pramanik, Shailendra Kumar Dhar Dwivedi, Fiifi Neizer-Ashun, Tamas Kiss, Abhrajit Ganguly, Heather Rice, Priyabrata Mukherjee, Chao Xu, Mohiuddin Ahmad, Anna Csiszar, Resham Bhattacharya
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Redox Biology, Vol 68, Iss , Pp 102958- (2023)
Druh dokumentu: article
ISSN: 2213-2317
DOI: 10.1016/j.redox.2023.102958
Popis: Astrocytic dysfunction is central to age-related neurodegenerative diseases. However, the mechanisms leading to astrocytic dysfunction are not well understood. We identify that among the diverse cellular constituents of the brain, murine and human astrocytes are enriched in the expression of CBS. Depleting CBS in astrocytes causes mitochondrial dysfunction, increases the production of reactive oxygen species (ROS) and decreases cellular bioenergetics that can be partially rescued by exogenous H2S supplementation or by re-expressing CBS. Conversely, the CBS/H2S axis, associated protein persulfidation and proliferation are decreased in astrocytes upon oxidative stress which can be rescued by exogenous H2S supplementation. Here we reveal that in the aging brain, the CBS/H2S axis is downregulated leading to decreased protein persulfidation, together augmenting oxidative stress. Our findings uncover an important protective role of the CBS/H2S axis in astrocytes that may be disrupted in the aged brain.
Databáze: Directory of Open Access Journals