Serotonin and 5-HT3 receptors sensitize human skin cells to direct irradiation cell death but not to soluble radiation-induced bystander signals

Curtis, Jacob J.; Vo, Nguyen T. K.; Seymour, Colin; Mothersill, Carmel

doi:10.1016/j.envres.2019.108807

Cited by 7 publications

(6 citation statements)

References 45 publications

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“…We have carefully chosen three cell lines, specifically, the human epidermal keratinocyte line (HaCaT), murine mammary carcinoma (4t1), and musculus mastocytoma (P185) for in vitro detection of ST. Optical micrographs of the selected cell lines are presented in Figure A–C. HaCaT is a nontumorigenic cell line and shows distinguished keratinocyte in vivo features with functional protein 53 . ST may act as a mitogen which is associated with cell proliferation and can be used as a biomarker to investigate radiation-induced cell death in HaCaT keratinocytes .…”

Section: Resultsmentioning

confidence: 99%

Rice-Spikelet-like Copper Oxide Decorated with Platinum Stranded in the CNT Network for Electrochemical In Vitro Detection of Serotonin

Ashraf

Asif

Aziz

et al. 2021

ACS Appl. Mater. Interfaces

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The specific monitoring of serotonin (ST) has provoked massive interest in therapeutic and biological science since it has been recognized as the third most significant endogenous gastrointestinal neurotransmitter. Hence, there is a great need to develop a sensitive and low-cost sensing platform for the detection of a clinically relevant ST level in biological matrices. Herein, we develop a simple two-step approach for an ultrasensitive electrochemical (EC) sensor with the Cu2O metal oxide (MO)-incorporated CNT core that has been further deposited with a transitional amount of platinum nanoparticles (Pt NPs). We presented, for the first time, the deposition of Pt NPs on the (CNTs-Cu2O-CuO) nanopetal composite via the galvanic replacement method, where copper not only acts as a reductant but a sacrificial template as well. The electrocatalytic aptitude of the fabricated EC sensing platform has been assessed for the sensitive detection of ST as a proficient biomarker in early disease diagnostics. The synergy of improved active surface area, remarkable conductivity, polarization effect induced by Pt NPs on CNTs-Cu2O-CuO nanopetals, fast electron transfer, and mixed-valence states of copper boost up the redox processes at the electrode–analyte junction. The CNTs-Cu2O-CuO@Pt-modified electrode has unveiled outstanding electrocatalytic capabilities toward ST oxidation in terms of a low detection limit of 3 nM (S/N = 3), wide linear concentration range, reproducibility, and incredible durability. Owing to the amazing proficiency, the proposed EC sensor based on the CNTs-Cu2O-CuO@Pt heterostructure has been applied for ST detection in biotic fluids and real-time tracking of ST efflux released from various cell lines as early disease diagnostic approaches.

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Section: Resultsmentioning

confidence: 99%

Rice-Spikelet-like Copper Oxide Decorated with Platinum Stranded in the CNT Network for Electrochemical In Vitro Detection of Serotonin

Ashraf

Asif

Aziz

et al. 2021

ACS Appl. Mater. Interfaces

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“…Next, the effects of NRF2 status on radiation-induced dermatitis in vitro were assessed using an siRNA-based knockdown approach and subsequent measurement of sensitization of skin keratinocytes (HaCaT cells) to IR-induced cell death. Numerous prior studies have used HaCaT skin keratinocytes as a valid cellular model to study cutaneous effects of ionizing radiation [ [42] , [43] , [44] , [45] , [46] , [47] ]. Specifically, at 24 h post radiation, cell confluence decreased approximately 20% in NRF2 knockdown HaCaT cells ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Activation of NRF2 by topical apocarotenoid treatment mitigates radiation-induced dermatitis

et al. 2020

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Radiation therapy is a frontline treatment option for cancer patients; however, the effects of radiotherapy on non-tumor tissue (e.g. radiation-induced dermatitis) often worsen patient quality of life. Previous studies have implicated the importance of redox balance in preventing dermatitis, specifically in reference to modulation of the nuclear factor (erythroid-derived 2)-like 2 (NRF2) signaling pathway. Due to the cytoprotective functions of transcriptional target genes of NRF2, we investigated how modulation of NRF2 expression could affect DNA damage, oxidative stress, and cell viability in response to radiotherapy. Specifically, it was noted that NRF2 knockdown sensitized human skin keratinocytes to ionizing radiation; likewise, genetic ablation of NRF2 in vivo increased radiosensitivity of murine epidermis. Oppositely, pharmacological induction of NRF2 via the apocarotenoid bixin lowered markers of DNA damage and oxidative stress, while preserving viability in irradiated keratinocytes. Mechanistic studies indicated that topical pretreatment using bixin as an NRF2 activator antagonized initial DNA damage by raising cellular glutathione levels. Additionally, topical application of bixin prevented radiation-induced dermatitis, epidermal thickening, and oxidative stress in the skin of SKH1 mice. Overall, these data indicate that NRF2 is critical for mitigating the harmful skin toxicities associated with ionizing radiation, and that topical upregulation of NRF2 via bixin could prevent radiation-induced dermatitis.

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“…5-HT 3 antagonists reduce the severity of serotonin-induced skin itch [ 131 ] and neuraxial opioid-induced pruritus [ 132 ]. Direct irradiation cell death evoked by serotonin in keratinocytes is mediated through 5-HT 3 receptors, thus identifying these as a potential target for ameliorating ionizing radiation damage [ 133 ].…”

Section: Distribution Of 5-ht 3 Receptorsmentioning

confidence: 99%

Tapping into 5-HT3 Receptors to Modify Metabolic and Immune Responses

Irving

Turek

Kettle

et al. 2021

IJMS

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5-hydroxytryptamine type 3 (5-HT3) receptors are ligand gated ion channels, which clearly distinguish their mode of action from the other G-protein coupled 5-HT or serotonin receptors. 5-HT3 receptors are well established targets for emesis and gastrointestinal mobility and are used as adjunct targets in treating schizophrenia. However, the distribution of these receptors is wider than the nervous system and there is potential that these additional sites can be targeted to modulate inflammatory and/or metabolic conditions. Recent progress in structural biology and pharmacology of 5-HT3 receptors have provided profound insights into mechanisms of their action. These advances, combined with insights into clinical relevance of mutations in genes encoding 5-HT3 subunits and increasing understanding of their implications in patient’s predisposition to diseases and response to the treatment, open new avenues for personalized precision medicine. In this review, we recap on the current status of 5-HT3 receptor-based therapies using a biochemical and physiological perspective. We assess the potential for targeting 5-HT3 receptors in conditions involving metabolic or inflammatory disorders based on recent findings, underscoring the challenges and limitations of this approach.

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Serotonin and 5-HT3 receptors sensitize human skin cells to direct irradiation cell death but not to soluble radiation-induced bystander signals

Cited by 7 publications

References 45 publications

Rice-Spikelet-like Copper Oxide Decorated with Platinum Stranded in the CNT Network for Electrochemical In Vitro Detection of Serotonin

Rice-Spikelet-like Copper Oxide Decorated with Platinum Stranded in the CNT Network for Electrochemical In Vitro Detection of Serotonin

Activation of NRF2 by topical apocarotenoid treatment mitigates radiation-induced dermatitis

Tapping into 5-HT3 Receptors to Modify Metabolic and Immune Responses

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