Verma 2023 Int J Mol Sci
Verma A, Azhar G, Zhang X, Patyal P, Kc G, Sharma S, Che Y, Wei JY (2023) P. gingivalis-LPS induces mitochondrial dysfunction mediated by neuroinflammation through oxidative stress. Int J Mol Sci 24:950. https://doi.org/10.3390/ijms24020950 |
Verma Ambika, Azhar Gohar, Zhang Xiaomin, Patyal Pankaj, Kc Grishma, Sharma Shakshi, Che Yingni, Wei Jeanne Y (2023) Int J Mol Sci
Abstract: Porphyromonas gingivalis (P. gingivalis), a key pathogen in periodontitis, is associated with neuroinflammation. Periodontal disease increases with age; 70.1% of adults 65 years and older have periodontal problems. However, the P. gingivalis- lipopolysaccharide (LPS)induced mitochondrial dysfunction in neurodegenerative diseases remains elusive. In this study, we investigated the possible role of P. gingivalis-LPS in mitochondrial dysfunction during neurodegeneration. We found that P. gingivalis-LPS treatment activated toll-like receptor (TLR) 4 signaling and upregulated the expression of Alzheimer's disease-related dementia and neuroinflammatory markers. Furthermore, the LPS treatment significantly exacerbated the production of reactive oxygen species and reduced the mitochondrial membrane potential. Our study highlighted the pivotal role of P. gingivalis-LPS in the repression of serum response factor (SRF) and its co-factor p49/STRAP that regulate the actin cytoskeleton. The LPS treatment repressed the genes involved in mitochondrial function and biogenesis. P. gingivalis-LPS negatively altered oxidative phosphorylation and glycolysis and reduced total adenosine triphosphate (ATP) production. Additionally, it specifically altered the mitochondrial functions in complexes I, II, and IV of the mitochondrial electron transport chain. Thus, it is conceivable that P. gingivalis-LPS causes mitochondrial dysfunction through oxidative stress and inflammatory events in neurodegenerative diseases. β’ Keywords: P. gingivalis-LPS, Mitochondrial dysfunction, Neuroinflammation, Oxidative stress β’ Bioblast editor: Plangger M
Labels: MiParea: Respiration
Pathology: Neurodegenerative
Organism: Human Tissue;cell: Endothelial;epithelial;mesothelial cell Preparation: Permeabilized cells, Intact cells
Coupling state: LEAK, ROUTINE, OXPHOS, ET
Pathway: N, S, CIV, ROX
HRR: Oxygraph-2k
2024-03