N -(3-oxododecanoyl)- l -homoserine lactone modulates mitochondrial function and suppresses proliferation in intestinal goblet cells

Tao, Shiyu; Niu, Liqiong; Cai, Liuping; Yang, Geng; Hua, Chenlei; Ni, Yingdong; Zhao, Ruqian

doi:10.1016/j.lfs.2018.03.049

Cited by 26 publications

(12 citation statements)

References 48 publications

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“…Interestingly, Tao et al . found that 3-oxo-C12-HSL enhanced activity of the respiratory complexes IV and V in intestinal goblet cells 35 . This suggests that there may be cell type- and tissue- specific effects of QS molecules on cellular bioenergetics, which may contribute to the predilection of P .…”

Section: Discussionmentioning

confidence: 95%

Pseudomonas aeruginosa Induced Host Epithelial Cell Mitochondrial Dysfunction

Maurice

Bedi

Yuan

et al. 2019

Sci Rep

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The pathogenicity of P . aeruginosa is dependent on quorum sensing (QS), an inter-bacterial communication system that can also modulate host biology. The innate immune function of the lung mucosal barrier is dependent on proper mitochondrial function. The purpose of this study was to define the mechanism by which bacterial factors modulate host lung epithelial cell mitochondrial function and to investigate novel therapies that ameliorate this effect. 3-oxo-C12-HSL disrupts mitochondrial morphology, attenuates mitochondrial bioenergetics, and induces mitochondrial DNA oxidative injury. Mechanistically, we show that 3-oxo-C12-HSL attenuates expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), a master regulator of mitochondrial biogenesis, antioxidant defense, and cellular respiration, and its downstream effectors in both BEAS-2B and primary lung epithelial cells. Overexpression of PGC-1α attenuates the inhibition in cellular respiration caused by 3-oxo-C12-HSL. Pharmacologic activation of PGC-1α restores barrier integrity in cells treated with 3-oxo-C12-HSL. These data demonstrate that the P . aeruginosa QS molecule, 3-oxo-C12-HSL, alters mitochondrial pathways critical for lung mucosal immunity. Genetic and pharmacologic strategies that activate the PGC-1α pathway enhance host epithelial cell mitochondrial function and improve the epithelial innate response to P . aeruginosa . Therapies that rescue PGC-1α function may provide a complementary approach in the treatment of P . aeruginosa infection.

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Section: Discussionmentioning

confidence: 95%

Pseudomonas aeruginosa Induced Host Epithelial Cell Mitochondrial Dysfunction

Maurice

Bedi

Yuan

et al. 2019

Sci Rep

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“…30 Goblet cells are scattered amongst epithelial cells, especially in the respiratory and gastrointestinal tracts, and secrete high molecular mass mucins to form viscous gels that trap microbes and irritants and limit their spread to the epithelium. 31,32 Previous studies have shown that excessive secretion of mucin is associated with inflammation caused by bacterial infection. 33 Due to their high safety and low cost, natural products and their derivatives are increasingly used in combating human diseases.…”

Section: Discussionmentioning

confidence: 99%

The protective effect of icariin and phosphorylated icariin against LPS-induced intestinal goblet cell dysfunction

Xiong

Zhu

et al. 2019

Innate Immun

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In this study, we used LS174T cells as a model to investigate the protective effects of icariin and phosphorylated icariin on LPS-induced goblet cell dysfunction. Our results indicated that icariin and phosphorylated icariin increased the cell viability and decreased lactate dehydrogenase activity in LPS-treated LS174T cells. Icariin and phosphorylated icariin attenuated LPS-induced changes in mucin 2 synthesis and secretion. Besides, Icariin and phosphorylated icariin reduced the levels of ROS, MDA, and H2O2 and increased the activity of SOD, GPx, CAT, and T-AOC in LPS-treated LS174T cells. Moreover, the levels of IL-1β, IL-6, IL-8, and TNF-α were reduced in the Icariin and phosphorylated icariin group. Furthermore, Icariin and phosphorylated icariin decreased gene abundance or enzyme activity of Bip, XBP1, GRP78, CHOP, caspase-3, and caspase-4 in LPS-treated LS174T cells. Our data suggest that Icariin and phosphorylated icariin effectively attenuate LPS-induced intestinal goblet cell function damage through regulating oxidative stress, inflammation, apoptosis, and mucin expression.

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“…ATP synthase of complex V was upregulated in fibroblasts in response to 3O-C 12 -HSL ( Supplementary Table S4). It has been reported also that 3O-C 12 -HSL can enhance the activity of complexes IV and V in intestinal goblet cell (Tao et al, 2018), suggesting that ETC complexes may undergo different fates in 3O-C 12 -HSL-treated cells. Interestingly, ATP synthase of complex V appears as dimers in the cristae and are responsible for its folding and curvature and thus for the large increase in available surface, that makes mitochondria efficient in energy production (Strauss et al, 2008).…”

Section: Discussionmentioning

confidence: 96%

Pseudomonas aeruginosa N-3-Oxo-Dodecanoyl-Homoserine Lactone Impacts Mitochondrial Networks Morphology, Energetics, and Proteome in Host Cells

et al. 2020

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Mitochondria play crucial roles in cellular metabolism, signaling, longevity, and immune defense. Recent evidences have revealed that the host microbiota, including bacterial pathogens, impact mitochondrial behaviors and activities in the host. The pathogenicity of Pseudomonas aeruginosa requires quorum sensing (QS) cell-cell communication allowing the bacteria to sense population density and collectively control biofilm development, virulence traits, adaptation and interactions with the host. QS molecules, like N-3-oxo-dodecanoyl-L-homoserine lactone (3O-C 12-HSL), can also modulate the behavior of host cells, e.g., epithelial barrier properties and innate immune responses. Here, in two types of cells, fibroblasts and intestinal epithelial cells, we investigated whether and how P. aeruginosa 3O-C 12-HSL impacts the morphology of mitochondrial networks and their energetic characteristics, using high-resolution transmission electron microscopy, fluorescence live-cell imaging, assay for mitochondrial bioenergetics, and quantitative mass spectrometry for mitoproteomics and bioinformatics. We found that 3O-C 12-HSL induced fragmentation of mitochondria, disruption of cristae and inner membrane ultrastructure, altered major characteristics of respiration and energetics, and decreased mitochondrial membrane potential, and that there are distinct cell-type specific details of these effects. Moreover, this was mechanistically accompanied by differential expression of both common and cell-type specific arrays of components in the mitochondrial proteome involved in their structural organization, electron transport chain complexes and response to stress. We suggest that this effect of 3O-C 12-HSL on mitochondria may represent one of the events in the interaction between P. aeruginosa and host mitochondria and may have an impact on the pathogens strategy to hijack host cell activities to support their own survival and spreading.

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N -(3-oxododecanoyl)- l -homoserine lactone modulates mitochondrial function and suppresses proliferation in intestinal goblet cells

Cited by 26 publications

References 48 publications

Pseudomonas aeruginosa Induced Host Epithelial Cell Mitochondrial Dysfunction

Pseudomonas aeruginosa Induced Host Epithelial Cell Mitochondrial Dysfunction

The protective effect of icariin and phosphorylated icariin against LPS-induced intestinal goblet cell dysfunction

Pseudomonas aeruginosa N-3-Oxo-Dodecanoyl-Homoserine Lactone Impacts Mitochondrial Networks Morphology, Energetics, and Proteome in Host Cells

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