Frontiers in Cell and Developmental Biology (Oct 2020)
Peroxisomal Dysfunction Contributes to White Matter Injury Following Subarachnoid Hemorrhage in Rats via Thioredoxin-Interacting Protein-Dependent Manner
Abstract
Background and PurposeWhite matter injury (WMI) exists in the early stage of subarachnoid hemorrhage (SAH) and has not been well addressed so far.MethodsWe utilized short hairpin RNA (shRNA) and clustered regularly interspaced short palindromic repeats (CRISPR) to verify the role of peroxisomes in WMI following SAH. We evaluated short- and long-term neurobehavior after SAH. Western blotting, immunofluorescence, and Golgi staining techniques were performed to assess the changes in protein levels.ResultsCatalase (CAT) CRISPR treatment significantly attenuated neurological deficits and reduced long-term spatial learning and memory impairments after SAH by increasing the level of myelin basic protein (MBP) while decreasing the levels of amyloid precursor protein (APP), interleukin 6 (IL-6), and tumor necrosis factor (TNF)-α. The use of thioredoxin-interacting protein (TXNIP) shRNA significantly offset the effects of CAT shRNA, and the use of glycerone phosphate acyl transferase (GNPAT) shRNA significantly reversed the effects of CAT CRISPR by decreasing the levels of plasmalogens and reactive oxidative species (ROS).ConclusionPeroxisomal dysfunction induced by SAH reversely exacerbated cerebral WMI following SAH, which was at least partly mediated by TXNIP and GNPAT pathways.
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