S1P Signalling Axis Is Necessary for Adiponectin-Directed Regulation of Electrophysiological Properties and Oxidative Metabolism in C2C12 Myotubes

Bernacchioni, Caterina; Squecco, Roberta; Gamberi, Tania; Ghini, Veronica; Schumacher, Fabian; Mannelli, Michele; Garella, Rachele; Idrizaj, Eglantina; Cencetti, Francesca; Puliti, Elisa; Bruni, Paola; Turano, Paola; Fiaschi, Tania; Donati, Chiara

doi:10.3390/cells11040713

Cited by 10 publications

(9 citation statements)

References 83 publications

(108 reference statements)

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“…SK1 and SK2, characterized by different tissue distribution and subcellular localization, can modulate fundamental cellular processes, such as apoptosis and proliferation, even in opposite ways [35]. Our findings support the concept that SK isoforms may have overlapping functions, as already reported for the pro-myogenic action exerted by IGF [36] and for the modulation of electrophysiological properties and oxidative metabolism by adiponectin in skeletal muscle [37]. Of note, SK1 and SK2 are equally required for the chemotactic effect exerted by epidermal growth factor (EGF) in breast cancer cells [38] and by TGFβ in esophageal cancer cells [39].…”

Section: Discussionsupporting

confidence: 87%

Sphingosine 1‐phosphate signaling axis mediates neuropeptide S‐induced invasive phenotype of endometriotic cells

Prisinzano,

Bernacchioni,

Seidita

et al. 2024

The FEBS Journal

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Endometriosis is a chronic gynecological syndrome characterized by endometrial cell invasion of the extra‐uterine milieu, pelvic pain and infertility. Treatment relies on either symptomatic drugs or hormonal therapies, even though the mechanism involved in the onset of endometriosis is yet to be elucidated. The signaling of sphingolipid sphingosine 1‐phosphate (S1P) is profoundly dysregulated in endometriosis. Indeed, sphingosine kinase (SK)1, one of the two isoenzymes responsible for S1P biosynthesis, and S1P1, S1P3 and S1P5, three of its five specific receptors, are more highly expressed in endometriotic lesions compared to healthy endometrium. Recently, missense coding variants of the gene encoding the receptor 1 for neuropeptide S (NPS) have been robustly associated with endometriosis in humans. This study aimed to characterize the biological effect of NPS in endometriotic epithelial cells and the possible involvement of the S1P signaling axis in its action. NPS was found to potently induce cell invasion and actin cytoskeletal remodeling. Of note, the NPS‐induced invasive phenotype was dependent on SK1 and SK2 as well as on S1P1 and S1P3, given that the biological action of the neuropeptide was fully prevented when one of the two biosynthetic enzymes or one of the two selective receptors was inhibited or silenced. Furthermore, the RhoA/Rho kinase pathway, downstream to S1P receptor signaling, was found to be critically implicated in invasion and cytoskeletal remodeling elicited by NPS. These findings provide new information to the understanding of the molecular mechanisms implicated in endometriosis pathogenesis, establishing the rationale for non‐hormonal therapeutic targets for its treatment.

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Section: Discussionsupporting

confidence: 87%

Sphingosine 1‐phosphate signaling axis mediates neuropeptide S‐induced invasive phenotype of endometriotic cells

Prisinzano,

Bernacchioni,

Seidita

et al. 2024

The FEBS Journal

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“…This outcome is in agreement with previous observations on atrophic myotubes made by our research group. Indeed, atrophic myotubes showed an increased membrane permeability and a reduction of cell capacitance 16 . Here, we demonstrate that the presence of sodium pyruvate in CM CT26 counteracted the occurence of these alterations, showing membrane parameters similar to untreated myotubes.…”

Section: Discussionmentioning

confidence: 52%

“…When filled, the patch pipette's resistance was 1.5–2 MΩ. The patch pipette was inserted in a CV203BU head‐stage (Axon Instruments, Foster City, CA) attached to a three‐way coarse manipulator and micro‐manipulator (Narishige, Tokyo, Japan) and an Axopatch 200 B amplifier (Axon Instruments, Foster City, CA) as previously described 16 . Voltage‐clamp protocol generation and data acquisition were managed by the A/D‐D/A interfaces (Digidata 1200; Axon Instruments) and Pclamp 6 software (Axon Instruments Foster City, CA).…”

Section: Methodsmentioning

confidence: 99%

“…The patch pipette was inserted in a CV203BU head-stage (Axon Instruments, Foster City, CA) attached to a three-way coarse manipulator and micromanipulator (Narishige, Tokyo, Japan) and an Axopatch 200 B amplifier (Axon Instruments, Foster City, CA) as previously described. 16 Voltage-clamp protocol generation and data acquisition were managed by the A/D-D/A interfaces (Digidata 1200; Axon Instruments) and Pclamp 6 software (Axon Instruments Foster City, CA). Starting from a holding potential (HP) of −70 mV, we applied a 10-mV negative and positive step pulse to evoke only the passive currents, consisting of an early capacitive transient (I c ) followed by a steady resistive current (I r ).…”

Section: Electrophysiological Analysismentioning

confidence: 99%

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Pyruvate prevents the onset of the cachectic features and metabolic alterations in myotubes downregulating STAT3 signaling

et al. 2022

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Cachexia is a systemic disease associated with several pathologies, including cancer, that leads to excessive weight loss due to enhanced protein degradation. Previously, we showed that cachectic features in myotubes are provoked by a metabolic shift toward lactic fermentation. Our previous results led us to hyphotesise that increasing pyruvate concentration could impede the metabolic modifications responsible for induction of cachexia in myotubes. Here, we demonstrated that the addition of sodium pyruvate in conditioned media from CT26 colon cancer cells (CM CT26) prevents the onset of either phenotypic and metabolic cachectic features. Myotubes treated with CM CT26 containing sodium pyruvate show a phenotype similar to the healthy counterpart and display lactate production, oxygen consumption, and pyruvate dehydrogenase activity as control myotubes. The use of the Mitochondrial Pyruvate Carrier inhibitor UK5099, highlights the importance of mitochondrial pyruvate amount in the prevention of cachexia. Indeed, UK5099‐treated myotubes show cachectic features as those observed in myotubes treated with CM CT26. Finally, we found that sodium pyruvate is able to decrease STAT3 phosphorylation level, a signaling pathway involved in the induction of cachexia in myotubes. Collectively, our results show that cachexia in myotubes could be prevented by the utilization of sodium pyruvate which impedes the metabolic modifications responsible for the acquisition of the cachectic features.

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“…Sphingosine, an important member of sphingolipids, is a ubiquitous component of the cell membrane and serves a pivotal role in cell growth, metabolism regulation, signal transduction, and various physiological function ( Gaggini et al, 2022 ; Grewe et al, 2022 ). Previous publications demonstrated that sphingosine and sphingosine-1-phosphate (its downstream product) were bioactive biomolecules which exerted proinflammatory effects and promoted proapoptotic properties in the vascular endothelial cell, contributing to the occurrence and development of cardiovascular diseases ( Bernacchioni et al, 2022 ; Kurano et al, 2022 ). In recent studies, sphingosine levels were proven to be shifted in the inner tissues and perilymph and aggravated the oxidative stress and inflammation in sensorineural hearing loss and ototoxicity ( Romero-Guevara et al, 2015 ; Cencetti et al, 2019 ; Wang et al, 2020 ; Ramkumar et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Diagnostic and predictive values of serum metabolic profiles in sudden sensorineural hearing loss patients

Wang

Gao

Jiang

2022

Front. Mol. Biosci.

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Sudden sensorineural hearing loss (SSNHL) is an otologic emergency, and metabolic disturbance is involved in its pathogenesis. This study recruited 20 SSNHL patients and 20 healthy controls (HCs) and collected their serum samples. Serum metabolites were detected by liquid chromatography-mass spectrometry, and metabolic profiles were analyzed. All patients were followed up for 3 months and categorized into recovery and non-recovery groups. The distinctive metabolites were assessed between two groups, and their predictive values for hearing recovery were evaluated. Analysis results revealed that SSNHL patients exhibited significantly characteristic metabolite signatures compared to HCs. The top 10 differential metabolites were further analyzed, and most of them showed potential diagnostic values based on receiver operator characteristic (ROC) curves. Finally, 14 SSNHL patients were divided into the recovery group, and six patients were included in the non-recovery group. Twelve distinctive metabolites were observed between the two groups, and ROC curves demonstrated that N4-acetylcytidine, p-phenylenediamine, sphingosine, glycero-3-phosphocholine, and nonadecanoic acid presented good predictabilities in the hearing recovery. Multivariate analysis results demonstrated that serum N4-Acetylcytidine, sphingosine and nonadecanoic acid levels were associated with hearing recovery in SSNHL patients. Our results identified that SSNHL patients exhibited distinctive serum metabolomics signatures, and several serum biomarkers were proved to be potential in predicting hearing recovery. The discriminative metabolites might contribute to illustrating the mechanisms of SSNHL and provide possible clues for its treatments.

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S1P Signalling Axis Is Necessary for Adiponectin-Directed Regulation of Electrophysiological Properties and Oxidative Metabolism in C2C12 Myotubes

Cited by 10 publications

References 83 publications

Sphingosine 1‐phosphate signaling axis mediates neuropeptide S‐induced invasive phenotype of endometriotic cells

Sphingosine 1‐phosphate signaling axis mediates neuropeptide S‐induced invasive phenotype of endometriotic cells

Pyruvate prevents the onset of the cachectic features and metabolic alterations in myotubes downregulating STAT3 signaling

Diagnostic and predictive values of serum metabolic profiles in sudden sensorineural hearing loss patients

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