Olfactory receptor signaling

Antunes, Gabriela; Fm, Simoes de Souza

doi:10.1016/bs.mcb.2015.11.003

Cited by 34 publications

(28 citation statements)

References 153 publications

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“…A previous report [ 16 ] showed that activation of OR2AT4 by Sandalore ® in keratinocytes triggers an intracellular transduction pathway leading to an increase in cAMP levels. cAMP is described as the canonical downstream messenger released by OR activation during olfaction [ 3 ]. Rose extract also triggers a dose-dependent increase in cAMP levels in keratinocytes expressing OR10A6, OR11H4, and OR2AG2.…”

Section: Discussionmentioning

confidence: 99%

“…ORs are encoded by the largest multigene family in mammals with 396 intact OR genes and 425 OR pseudogenes corresponding to a sequence with a nonsense mutation, frameshift, and deletion within conserved regions [ 2 ]. ORs are mainly located in the olfactory epithelium and mediate the first step in odor recognition [ 3 , 4 , 5 ]. Several studies suggest that every human individual is characterized by a different combination of OR-segregating pseudogenes [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

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A Rose Extract Protects the Skin against Stress Mediators: A Potential Role of Olfactory Receptors

et al. 2020

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Olfactory receptors (ORs) are expressed and active in various human tissues, including the skin. Although the sense of smell plays an important physiological role in the regulation of mood and stress, a link between olfactive compounds, ORs, and skin stress has yet to be established. This study aims to investigate the role of newly identified skin ORs and agonists in the modulation of skin stress. Screening for odorant molecules was done with cAMP functional assay to identify OR agonists. RT-qPCR and immunofluorescence microscopy were conducted to identify and quantify ORs in epidermal keratinocytes (NHEKs) and human skin explants, as well as to evaluate specific markers (G6PDH, loricrin, and γH2AX) of stress-induced skin alterations. A randomized double-blinded, split-face clinical study was performed on a panel of stressed women to measure the benefits of OR agonist treatment for skin. Three new ORs (OR10A6, OR2AG2, and OR11H4) were identified in skin. A specific Rose extract and its major constituent (phenylethyl alcohol) were found to activate these ORs. The extract composition was revealed by both GC/FID and GC/MS analyses simultaneously and showed the presence of 34 volatiles molecules. Moreover, epinephrine induces a skin stress response characterized by increased expression of G6PD, loricrin, and γH2AX biomarkers, and a decrease of OR expression. These effects were prevented in the presence of rose extract and its benefits were confirmed clinically by a decrease in the appearance of under-eye dark circles. Altogether, our findings suggest that ORs may represent a new, promising way to treat stress-associated skin disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Rose Extract Protects the Skin against Stress Mediators: A Potential Role of Olfactory Receptors

et al. 2020

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“…Conventional nasal olfaction is mediated through ORs, which are found on olfactory epithelium located on the cilia of olfactory sensory neurons in the nasal cavity. 19 ORs are also expressed ectopically in nonolfactory tissues, such as the gut, skeletal muscle, testes, brain, and skin, where they can perform additional physiologic functions apart from olfaction. 20 Transcriptomic data from this study showed that 381 OR gene transcripts were detected in the dermis, epidermis, and skin tape-stripped samples of patients with AD and HC subjects, predominantly in the skin tape-stripped samples that correspond to the upper granular layer of the epidermis.…”

Section: Discussionmentioning

confidence: 99%

“…Exposure of olfactory epithelium to odorants results in activation of ORs, and this induces cellular ATP production through activation of the adenylyl cyclase-ATP-cAMP pathway. 19 Thus we measured ATP production as an indicator of activation of this pathway in keratinocytes using the CellTiter-Glo Assay. Luminescence units (RLU) were recorded with a luminometer after 2 minutes of incubation with odorants.…”

Section: Or10g7-mediated Atp Responses To Odorant Stimulationmentioning

confidence: 99%

Expression and function of the ectopic olfactory receptor OR10G7 in patients with atopic dermatitis

Tham

Dyjack

Kim

et al. 2019

Journal of Allergy and Clinical Immunology

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Background: Ectopic olfactory receptors (ORs) are found in the skin, but their expression and biological function in normal skin and skin form patients with atopic dermatitis (AD) are unknown. Objectives: We sought to characterize the expression of ORs in the skin and assess OR-mediated biological responses of primary human keratinocytes in the presence of odorant ligands. Methods: OR expression was examined by using wholetranscriptome sequencing of skin tape strips collected from patients with AD and healthy control (HC) subjects. OR10G7 and filaggrin 1 (FLG-1) expression was analyzed by using RT-PCR and immunostaining in skin biopsy specimens and primary human keratinocytes from patients with AD and HC subjects. ATP and cyclic AMP production by control and OR10G7 small interfering RNA-transfected keratinocytes in response to odorant stimulation with acetophenone and eugenol was assessed. Results: A total of 381 OR gene transcripts were detected in the skin samples, with the greatest OR expression detected in the skin tape strips corresponding to the upper granular layer of the skin. OR10G7 expression was significantly increased in skin biopsy specimens from patients with AD compared with those from HC subjects (P 5 .01) and inversely correlated with FLG-1 expression (P 5 .009). OR10G7 expression was greatest in undifferentiated keratinocytes from patients with AD and was downregulated with progressive differentiation. Primary human keratinocytes produced ATP, an essential neurotransmitter in sensory pathways, in response to acetophenone and eugenol, odorants previously identified as potential ligands for this receptor. This response was abolished in OR10G7 small interfering RNA-transfected keratinocytes. Conclusions: OR10G7 is expressed at significantly greater levels in undifferentiated keratinocytes from patients with AD compared with HC subjects. OR10G7 is likely involved in transmission of skin-induced chemosensory responses to odorant stimulation, which might modulate differential nociceptive responses in AD skin.

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“…Our present studies showed that patients with and without clonal heterogeneity differed with regard to the expression of genes encoding olfactory receptor components and proteins involved in downstream signaling from G-protein coupled receptors (GPCRs) signaling. The olfactory receptors are a subset of the GPCRs [ 18 , 19 , 20 ]. Olfactory receptors are expressed in many tissues and by many different normal cells outside the olfactory system.…”

Section: Discussionmentioning

confidence: 99%

Clonal Heterogeneity Reflected by PI3K-AKT-mTOR Signaling in Human Acute Myeloid Leukemia Cells and Its Association with Adverse Prognosis

Nepstad

Hatfield

Tvedt

et al. 2018

Cancers

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Clonal heterogeneity detected by karyotyping is a biomarker associated with adverse prognosis in acute myeloid leukemia (AML). Constitutive activation of the phosphatidylinositol-3-kinase-Akt-mechanistic target of rapamycin (PI3K-Akt-mTOR) pathway is present in AML cells, and this pathway integrates signaling from several upstream receptors/mediators. We suggest that this pathway reflects biologically important clonal heterogeneity. We investigated constitutive PI3K-Akt-mTOR pathway activation in primary human AML cells derived from 114 patients, together with 18 pathway mediators. The cohort included patients with normal karyotype or single karyotype abnormalities and with an expected heterogeneity of molecular genetic abnormalities. Clonal heterogeneity reflected as pathway mediator heterogeneity was detected for 49 patients. Global gene expression profiles of AML cell populations with and without clonal heterogeneity differed with regard to expression of ectopic olfactory receptors (a subset of G-protein coupled receptors) and proteins involved in G-protein coupled receptor signaling. Finally, the presence of clonal heterogeneity was associated with adverse prognosis for patients receiving intensive antileukemic treatment. The clonal heterogeneity as reflected in the activation status of selected mediators in the PI3K-Akt-mTOR pathway was associated with a different gene expression profile and had an independent prognostic impact. Biological heterogeneity reflected in the intracellular signaling status should be further investigated as a prognostic biomarker in human AML.

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Olfactory receptor signaling

Cited by 34 publications

References 153 publications

A Rose Extract Protects the Skin against Stress Mediators: A Potential Role of Olfactory Receptors

A Rose Extract Protects the Skin against Stress Mediators: A Potential Role of Olfactory Receptors

Expression and function of the ectopic olfactory receptor OR10G7 in patients with atopic dermatitis

Clonal Heterogeneity Reflected by PI3K-AKT-mTOR Signaling in Human Acute Myeloid Leukemia Cells and Its Association with Adverse Prognosis

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