Small-chain fatty acid activates astrocytic odorant receptor Olfr920

Cho, TaeHo; Lee, ChaeEun; Lee, NaHye; Hong, Yeonchul; Koo, Jae Hyung

doi:10.1016/j.bbrc.2019.01.106

Cited by 18 publications

(10 citation statements)

References 33 publications

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“…ORs and the downstream targets Adcy3 and Gα olf are identified in cancer tissues and cells, indicating that the OR-mediated signaling pathway plays important roles in these tissues and cell types. Many lines of evidence suggest that OR51E2 could be utilized as a potential target for prostate cancer treatment [ 19 , 28 , 110 , 111 , 112 , 113 ] ( Figure 6 ). Overexpression of OR51E2 in a mouse model is demonstrated to accelerate the development and progression of prostate cancer along with the loss of PTEN [ 110 ].…”

Section: Biological Functions Of Ectopic Ors Responding To Odorant Compounds In the Non-chemosensory Tissuesmentioning

confidence: 99%

“…Many lines of evidence suggest that OR51E2 could be utilized as a potential target for prostate cancer treatment [ 19 , 28 , 110 , 111 , 112 , 113 ] ( Figure 6 ). Overexpression of OR51E2 in a mouse model is demonstrated to accelerate the development and progression of prostate cancer along with the loss of PTEN [ 110 ]. Upon β-ionone binding, OR51E2 reduces the proliferation of prostate cancer cells by causing phoshorylation of stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK) and p38 and promotes invasiveness of prostate cancer cells through Gβγ–PI3Kγ pathway [ 19 , 111 ].…”

Section: Biological Functions Of Ectopic Ors Responding To Odorant Compounds In the Non-chemosensory Tissuesmentioning

confidence: 99%

“…In addition, activation of OR51E2 enhances cellular transformation, leading to neuroendocrine trans-differentiation. The OR51E1 activation promotes cellular senescence and inhibits the proliferation of prostate cancer cells, adapted from [ 110 , 113 ], published by Elsevier, 2019 and Elsevier, 2018. ( B ) Stimulation of OR51E2 suppresses the migration and proliferation of human melanoma cells [ 114 ], published by American Society for Biochemistry and Molecular Biology, 2011.…”

Section: Figurementioning

confidence: 99%

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Ectopic Odorant Receptor Responding to Flavor Compounds: Versatile Roles in Health and Disease

et al. 2021

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Prompted by the ground-breaking discovery of the rodent odorant receptor (OR) gene family within the olfactory epithelium nearly 30 years ago, followed by that of OR genes in cells of the mammalian germ line, and potentiated by the identification of ORs throughout the body, our appreciation for ORs as general chemoreceptors responding to odorant compounds in the regulation of physiological or pathophysiological processes continues to expand. Ectopic ORs are now activated by a diversity of flavor compounds and are involved in diverse physiological phenomena varying from adipogenesis to myogenesis to hepatic lipid accumulation to serotonin secretion. In this review, we outline the key biological functions of the ectopic ORs responding to flavor compounds and the underlying molecular mechanisms. We also discuss research opportunities for utilizing ectopic ORs as therapeutic strategies in the treatment of human disease as well as challenges to be overcome in the future. The recognition of the potent function, signaling pathway, and pharmacology of ectopic ORs in diverse tissues and cell types, coupled with the fact that they belong to G protein-coupled receptors, a highly druggable protein family, unequivocally highlight the potential of ectopic ORs responding to flavor compounds, especially food-derived odorant compounds, as a promising therapeutic strategy for various diseases.

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Section: Biological Functions Of Ectopic Ors Responding To Odorant Compounds In the Non-chemosensory Tissuesmentioning

confidence: 99%

Section: Biological Functions Of Ectopic Ors Responding To Odorant Compounds In the Non-chemosensory Tissuesmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

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Ectopic Odorant Receptor Responding to Flavor Compounds: Versatile Roles in Health and Disease

et al. 2021

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“…Branched chain fatty acids, including isovalerate and isobutyrate constitute a minor part of the total fatty acid composition where they are present as a result of amino acid degradation. Interestingly, more ORs are known, exhibiting response profiles for fatty acids produced by the microbiome, but these ORs have not yet been linked to intestinal physiology [152].…”

Section: Olfactory Receptors Emerging Intestinal Fatty Acid Sensors mentioning

confidence: 99%

The Intestinal Fatty Acid-Enteroendocrine Interplay, Emerging Roles for Olfactory Signaling and Serotonin Conjugates

Meijerink

2021

Molecules

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Intestinal enteroendocrine cells (EECs) respond to fatty acids from dietary and microbial origin by releasing neurotransmitters and hormones with various paracrine and endocrine functions. Much has become known about the underlying signaling mechanisms, including the involvement of G-protein coupled receptors (GPCRs), like free fatty acids receptors (FFARs). This review focusses on two more recently emerging research lines: the roles of odorant receptors (ORs), and those of fatty acid conjugates in gut. Odorant receptors belong to a large family of GPCRs with functional roles that only lately have shown to reach beyond the nasal-oral cavity. In the intestinal tract, ORs are expressed on serotonin (5-HT) and glucagon-like-peptide-1 (GLP-1) producing enterochromaffin and enteroendocrine L cells, respectively. There, they appear to function as chemosensors of microbiologically produced short-, and branched-chain fatty acids. Another mechanism of fatty acid signaling in the intestine occurs via their conjugates. Among them, conjugates of unsaturated long chain fatty acids and acetate with 5-HT, N-acyl serotonins have recently emerged as mediators with immune-modulatory effects. In this review, novel findings in mechanisms and molecular players involved in intestinal fatty acid biology are highlighted and their potential relevance for EEC-mediated signaling to the pancreas, immune system, and brain is discussed.

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“…Primary MG or AS were obtained from the brain cortex of E18.5 mouse (C57BL6/N; KOATECH, Pyeongtaek, Korea) embryos and cultured as previously described with slight modifications (DGIST-IACUC-19041202-02) [52,53]. Briefly, after dissection of the embryonic cortex, collected brains were stored in ice-cold Hanks' balanced salt solution (#14170-112; Thermo Fisher Scientific, Waltham, MA, USA) and digested with 0.25% trypsin (#15090-046; Thermo Fisher Scientific) for 20 min at 37°C.…”

Section: Culture Of Primary Microglia and Astrocytesmentioning

confidence: 99%

A pathogen‐derived metabolite induces microglial activation via odorant receptors

et al. 2020

Self Cite

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Microglia (MG), the principal neuroimmune sentinels in the brain, continuously sense changes in their environment and respond to invading pathogens, toxins, and cellular debris, thereby affecting neuroinflammation. Microbial pathogens produce small metabolites that influence neuroinflammation, but the molecular mechanisms that determine whether pathogen‐derived small metabolites affect microglial activation of neuroinflammation remain to be elucidated. We hypothesized that odorant receptors (ORs), the largest subfamily of G protein‐coupled receptors, are involved in microglial activation by pathogen‐derived small metabolites. We found that MG express high levels of two mouse ORs, Olfr110 and Olfr111, which recognize a pathogenic metabolite, 2‐pentylfuran, secreted by Streptococcus pneumoniae. These interactions activate MG to engage in chemotaxis, cytokine production, phagocytosis, and reactive oxygen species generation. These effects were mediated through the Gαs–cyclic adenosine monophosphate–protein kinase A–extracellular signal‐regulated kinase and Gβγ–phospholipase C–Ca2+ pathways. Taken together, our results reveal a novel interplay between the pathogen‐derived metabolite and ORs, which has major implications for our understanding of microglial activation by pathogen recognition. Database Model data are available in the PMDB database under the accession number PM0082389.

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Small-chain fatty acid activates astrocytic odorant receptor Olfr920

Cited by 18 publications

References 33 publications

Ectopic Odorant Receptor Responding to Flavor Compounds: Versatile Roles in Health and Disease

Ectopic Odorant Receptor Responding to Flavor Compounds: Versatile Roles in Health and Disease

The Intestinal Fatty Acid-Enteroendocrine Interplay, Emerging Roles for Olfactory Signaling and Serotonin Conjugates

A pathogen‐derived metabolite induces microglial activation via odorant receptors

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