The loss of antioxidant activities impairs intestinal epithelium homeostasis by altering lipid metabolism.
In: Experimental Cell Research, Jg. 437 (2024-04-01), Heft 1, S. N.PAG
academicJournal
Zugriff:
Reactive oxygens species (ROS) are common byproducts of metabolic reactions and could be at the origin of many diseases of the elderly. Here we investigated the role of ROS in the renewal of the intestinal epithelium in mice lacking catalase (CAT) and/or nicotinamide nucleotide transhydrogenase (NNT) activities. Cat −/− mice have delayed intestinal epithelium renewal and were prone to develop necrotizing enterocolitis upon starvation. Interestingly, crypts lacking CAT showed fewer intestinal stem cells (ISC) and lower stem cell activity than wild-type. In contrast, crypts lacking NNT showed a similar number of ISCs as wild-type but increased stem cell activity, which was also impaired by the loss of CAT. No alteration in the number of Paneth cells (PCs) was observed in crypts of either Cat −/− or Nnt −/− mice, but they showed an evident decline in the amount of lysozyme. Cat deficiency caused fat accumulation in crypts, and a fall in the remarkable high amount of adipose triglyceride lipase (ATGL) in PCs. Notably, the low levels of ATGL in the intestine of Cat −/− mice increased after a treatment with the antioxidant N-acetyl-L-cysteine. Supporting a role of ATGL in the regulation of ISC activity, its inhibition halt intestinal organoid development. These data suggest that the reduction in the renewal capacity of intestine originates from fatty acid metabolic alterations caused by peroxisomal ROS. Lack of catalase (Cat −/−) reduces intestinal stem cells (ISCs) in association with a reduction in lysozyme and ATGL lipase in Paneth cells, thus, decreasing epithelium renewal. This work propose that mitochondrial and peroxisomal fatty acid oxidation (m-FAO and p-FAO, respectively) decrease as peroxisomal H 2 O 2 accumulates in Paneth cells in the absence of catalase and causes ATGL lipase degradation. This condition attenuates mechanisms that positively regulate ISC stemness or activation. NNT possibly modifies the ROS threshold at which ISCs activate. [Display omitted] [ABSTRACT FROM AUTHOR]
Titel: |
The loss of antioxidant activities impairs intestinal epithelium homeostasis by altering lipid metabolism.
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Autor/in / Beteiligte Person: | Ramos-León, Javier ; Valencia, Concepción ; Gutiérrez-Mariscal, Mariana ; Rivera-Miranda, David-Alejandro ; García-Meléndrez, Celina ; Covarrubias, Luis |
Zeitschrift: | Experimental Cell Research, Jg. 437 (2024-04-01), Heft 1, S. N.PAG |
Veröffentlichung: | 2024 |
Medientyp: | academicJournal |
ISSN: | 0014-4827 (print) |
DOI: | 10.1016/j.yexcr.2024.113965 |
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