Association study identified biologically relevant receptor genes with synergistic functions in celiac disease

Banerjee, Pratibha; Bhagavatula, Sandilya; Sood, Ajit; Midha, Vandana; Thelma, B.K.; Senapati, Sabyasachi

doi:10.1038/s41598-019-50120-4

Cited by 5 publications

(4 citation statements)

References 37 publications

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“…A single nucleotide polymorphism of OR2H2, rs123388, was associated with patients with celiac disease in Indian and Dutch populations [29]. rs123388 and ve other polymorphisms were associated with immune functions and Toll-like receptor signaling pathways [29]. These results suggest a critical role for OR2H2 in gut and immune cells.…”

Section: Discussionmentioning

confidence: 94%

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OR2H2 Activation Suppresses Cellular Senescence and Aging by Activating AMPK and Inducing Senolysis in VK2/E6E7 Cells

Kim¹,

Dziobaka

Yoon³

et al. 2022

Preprint

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Background Olfactory receptors are expressed in multiple extra-nasal tissues and these ectopic olfactory receptors mediate tissue specific functions and regulate cellular physiology. Ectopic olfactory receptors may play key roles in tissues constantly exposed to odorants, thus functionality of these receptors in genital tissues are of particular interest. The functionality of ectopic olfactory receptors expressed in VK2/E6E7 human vaginal epithelial cells was investigated. Results OR2H2 was functionally expressed in VK2/E6E7 cells and activation of OR2H2 by aldehyde 13–13, a ligand of OR2H2, increased the intracellular calcium and cAMP concentrations. Immunoblotting demonstrated that activation of OR2H2 by aldehyde 13–13 stimulated the CAMKKβ-AMPK-mTOR-autophagy signaling axis, and that these effects were negated by OR2H2 knockdown. Autophagy activation suppressed aging and cellular senescence. Activation of OR2H2 by aldehyde 13–13 restored proliferation, reduced the expression of senescence markers, P16 and P19 in H2O2-induced senescent cells. Additionally, aldehyde 13–13 showed senolytic activity by predominantly inducing apoptosis of H2O2-induced senescent cells compared with non-senescent normal cells. In vivo, aldehyde 13–13 increased the lifespan of Caenorhabditis elegans and budding yeast. Conclusions These findings demonstrate that OR2H2 is a functional receptor in VK2/E6E7 cells and activation of OR2H2 activates AMPK-autophagy axis, suppresses cellular aging and senescence, thus may increase cellular lifespan.

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Section: Discussionmentioning

confidence: 94%

“…Aldehyde 13-13 suppressed proliferation of thyroid cancer cells [28]. A single nucleotide polymorphism of OR2H2, rs123388, was associated with patients with celiac disease in Indian and Dutch populations [29]. rs123388 and ve other polymorphisms were associated with immune functions and Toll-like receptor signaling pathways [29].…”

Section: Discussionmentioning

confidence: 99%

OR2H2 Activation Suppresses Cellular Senescence and Aging by Activating AMPK and Inducing Senolysis in VK2/E6E7 Cells

Kim¹,

Dziobaka

Yoon³

et al. 2022

Preprint

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show abstract

“…Aldehyde 13-13 inhibits the proliferation of thyroid cancer cells [ 28 ]. The single nucleotide polymorphism of OR2H2, rs123388, is linked to celiac disease in patients from Indian and Dutch populations [ 29 ]. This polymorphism, along with five others, is associated with immune functions and Toll-like receptor signaling pathways [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…The single nucleotide polymorphism of OR2H2, rs123388, is linked to celiac disease in patients from Indian and Dutch populations [ 29 ]. This polymorphism, along with five others, is associated with immune functions and Toll-like receptor signaling pathways [ 29 ]. Such findings indicate the significance of OR2H2 in gut and immune cells.…”

Section: Discussionmentioning

confidence: 99%

OR2H2 Activates CAMKKβ–AMPK–Autophagy Signaling Axis and Suppresses Senescence in VK2/E6E7 Cells

Kim,

Dziobaka,

Yoon

et al. 2023

Pharmaceuticals

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Olfactory receptors are expressed in multiple extra-nasal tissues and these ectopic olfactory receptors mediate tissue-specific functions and regulate cellular physiology. Ectopic olfactory receptors may play key roles in tissues constantly exposed to odorants, thus the functionality of these receptors in genital tissues is of particular interest. The functionality of ectopic olfactory receptors expressed in VK2/E6E7 human vaginal epithelial cells was investigated. OR2H2 was the most highly expressed olfactory receptor expressed in VK2/E6E7 cells, and activation of OR2H2 by aldehyde 13-13, a ligand of OR2H2, increased the intracellular calcium and cAMP concentrations. Immunoblotting demonstrated that activation of OR2H2 by aldehyde 13-13 stimulated the CAMKKβ–AMPK–mTORC1–autophagy signaling axis, and that these effects were negated by OR2H2 knockdown. AMPK is known to regulate senescence; consequently, we investigated further the effect of aldehyde 13-13 on senescence. In H2O2-induced senescent cells, activation of OR2H2 by aldehyde 13-13 restored proliferation, and reduced the expression of senescence markers, P16 and P19. Additionally, aldehyde 13-13 induced apoptosis of H2O2-induced senescent cells, compared with non-senescent normal cells. In vivo, aldehyde 13-13 increased the lifespan of Caenorhabditis elegans and budding yeast. These findings demonstrate that OR2H2 is a functional receptor in VK2/E6E7 cells, and that activation of OR2H2 activates the AMPK–autophagy axis, and suppresses cellular aging and senescence, which may increase cellular health.

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Staunch the Age Related Decline into Dementia, Cancer, Autoimmunity (Long Covid), Obesity, and Other Diseases with a Prebiotic, Probiotic, Postbiotic Triple Play

Chambers

2024

Qeios

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“All diseases originate in the gut.” Hippocrates (400 BC) A healthy gut microbiome via the gut-brain-axis elevates heart rate variability (HRV), a general measure of health and well-being. A dysbiotic gut microbiome, low in biodiversity and butyrate producers, can alter tryptophan metabolism (ATM) and increase the kynurenine to tryptophan ratio (KTR) with release of proinflammatory cytokines, predominantly TNF-α, IL-6, and IL-1β. These also characterize chronic inflammation, oxidative stress, and a multitude of diseases. Also proposed is the gut-lung dysbiosis concept and consequent degradation of ACE2 (richest in lungs and gut). Leaky gut (and lung) induced autoantibodies (AAs) related to G-protein coupled receptors (GPCRs) in combination with increased Ang II further potentiate oxidative stress. The underappreciated pathogenic role of Candida is explored. The efficacy of fecal microbiome transplantation (FMT) in treating dementia, cancer, and autoimmunity supports the plausibility of success with “FMT-lite”. This triple play of prebiotic (d-mannose), probiotic (bifidobacteria and lactobacilli), and postbiotic (butyrate) might improve intestinal barrier integrity, oppose entry of GPCR antigens, suppress the inflammatory cytokine triad, balance IFN-γ and TGF-β, suppress oxidative stress, depress KTR, elevate HRV, and extend lifespan and its quality.

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Association study identified biologically relevant receptor genes with synergistic functions in celiac disease

Cited by 5 publications

References 37 publications

OR2H2 Activation Suppresses Cellular Senescence and Aging by Activating AMPK and Inducing Senolysis in VK2/E6E7 Cells

OR2H2 Activation Suppresses Cellular Senescence and Aging by Activating AMPK and Inducing Senolysis in VK2/E6E7 Cells

OR2H2 Activates CAMKKβ–AMPK–Autophagy Signaling Axis and Suppresses Senescence in VK2/E6E7 Cells

Staunch the Age Related Decline into Dementia, Cancer, Autoimmunity (Long Covid), Obesity, and Other Diseases with a Prebiotic, Probiotic, Postbiotic Triple Play

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