Melatonin Reduces Mito-Inflammation in Ischaemic Hippocampal HT22 Cells and Modulates the cGAS-STING Cytosolic DNA Sensing Pathway and FGF21 Release.

Autor: Carloni S; Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy., Nasoni MG; Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy., Casabianca A; Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy.; Laboratorio Covid, University of Urbino Carlo Bo, Fano, Italy., Orlandi C; Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy.; Laboratorio Covid, University of Urbino Carlo Bo, Fano, Italy., Capobianco L; Department of Biological Science and Technology, University of Salento, Lecce, Italy., Iaconisi GN; Department of Biological Science and Technology, University of Salento, Lecce, Italy., Cerioni L; Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy., Burattini S; Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy., Benedetti S; Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy., Reiter RJ; Department of Cell Systems and Anatomy, Long School of Medicine, UT Health, San Antonio, Texas, USA., Balduini W; Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy., Luchetti F; Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy.
Jazyk: angličtina
Zdroj: Journal of cellular and molecular medicine [J Cell Mol Med] 2024 Dec; Vol. 28 (24), pp. e70285.
DOI: 10.1111/jcmm.70285
Abstrakt: Mitochondrial dysfunction is a key event in many pathological conditions, including neurodegenerative processes. When mitochondria are damaged, they release damage-associated molecular patterns (DAMPs) that activate mito-inflammation. The present study assessed mito-inflammation after in vitro oxygen-glucose deprivation as a representation of ischaemia, followed by reoxygenation (OGD/R) of HT22 cells and modulation of the inflammatory response by melatonin. We observed that melatonin prevented mitochondrial structural damage and dysfunction caused by OGD/R. Melatonin reduced oxidative damage and preserved the enzymatic activity for complexes I, III and IV, encoded by mitochondrial DNA, which were reduced by OGD/R. No effect was observed on complex II activity encoded by nuclear DNA. The release of mtDNA into the cytosol was also prevented with a consequent reduction of the cGAS-STING pathway and IFNβ and IL-6 production. Interestingly, melatonin also increased the early release of the fibroblast growth factor-21 (FGF-21), a mitokine secreted in response to mitochondrial stress. These data indicate that melatonin reduces mito-inflammation and modulates FGF-21 release, further highlighting the key role of this molecule in preserving mitochondrial integrity in OGD/R deprivation-type ischaemic brain injury.
(© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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