Solar light induces expression of acetylcholinesterase in skin keratinocytes: Signalling mediated by activator protein 1 transcription factor

Wu, Qiyun; Bai, Panzhu; Xia, Yingjie; Lai, Queenie Wing Sze; Guo, Maggie Suisui; Dai, Kun; Zheng, Zhongyu; Ling, Christine S.J.; Dong, Tina Tingxia; Tsim, Karl Wah Keung

doi:10.1016/j.neuint.2020.104861

Cited by 10 publications

(17 citation statements)

References 37 publications

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“…This, however, is unlikely since breast tumors were analyzed using the identical HRMAS 1 H-NMR technique [30] and no acetylcholine was detected. In addition, acetylcholine metabolizing enzymes and transporters could be analyzed at the protein level, since their expression and thus their function may not exclusively be regulated through transcription [58,59].…”

Section: General Versus Tet-specific Metabolitesmentioning

confidence: 99%

Metabolic Profiling of Thymic Epithelial Tumors Hints to a Strong Warburg Effect, Glutaminolysis and Precarious Redox Homeostasis as Potential Therapeutic Targets

Alwahsh

Knitsch

Marchan

et al. 2022

Cancers

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Thymomas and thymic carcinomas (TC) are malignant thymic epithelial tumors (TETs) with poor outcome, if non-resectable. Metabolic signatures of TETs have not yet been studied and may offer new therapeutic options. Metabolic profiles of snap-frozen thymomas (WHO types A, AB, B1, B2, B3, n = 12) and TCs (n = 3) were determined by high resolution magic angle spinning 1H nuclear magnetic resonance (HRMAS 1H-NMR) spectroscopy. Metabolite-based prediction of active KEGG metabolic pathways was achieved with MetPA. In relation to metabolite-based metabolic pathways, gene expression signatures of TETs (n = 115) were investigated in the public “The Cancer Genome Atlas” (TCGA) dataset using gene set enrichment analysis. Overall, thirty-seven metabolites were quantified in TETs, including acetylcholine that was not previously detected in other non-endocrine cancers. Metabolite-based cluster analysis distinguished clinically indolent (A, AB, B1) and aggressive TETs (B2, B3, TCs). Using MetPA, six KEGG metabolic pathways were predicted to be activated, including proline/arginine, glycolysis and glutathione pathways. The activated pathways as predicted by metabolite-profiling were generally enriched transcriptionally in the independent TCGA dataset. Shared high lactic acid and glutamine levels, together with associated gene expression signatures suggested a strong “Warburg effect”, glutaminolysis and redox homeostasis as potential vulnerabilities that need validation in a large, independent cohort of aggressive TETs. If confirmed, targeting metabolic pathways may eventually prove as adjunct therapeutic options in TETs, since the metabolic features identified here are known to confer resistance to cisplatin-based chemotherapy, kinase inhibitors and immune checkpoint blockers, i.e., currently used therapies for non-resectable TETs.

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Section: General Versus Tet-specific Metabolitesmentioning

confidence: 99%

Metabolic Profiling of Thymic Epithelial Tumors Hints to a Strong Warburg Effect, Glutaminolysis and Precarious Redox Homeostasis as Potential Therapeutic Targets

Alwahsh

Knitsch

Marchan

et al. 2022

Cancers

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“…The role of cholinergic system in mediating skin pigmentation has been reported, as forming a proposed 'skin synapse'. The exposure to UV is a stimulus to the release of ACh from keratinocytes [8,13]. On melanocytes, ACh functions as a negative regulator of melanogenesis via type 2 muscarinic AChR, which thereafter downregulates the expressions of melanogenic enzymes [14].…”

Section: Discussionmentioning

confidence: 99%

“…The method of protein extraction was described previously [8,13]. In brief, low-salt protein lysis buffer added with protease inhibitors, including benzamidine, aprotinin and leupeptin, and 0.5% Triton X-100 was used to lyse the cells.…”

Section: Sds/page and Western Blotting Analysismentioning

confidence: 99%

“…Cholinergic system has been characterized to be involved in basic skin functions, e.g. proliferation, differentiation, adhesion and migration of keratinocyte, formation of epidermal barrier, production of pigment, blood circulation, angiogenesis and a variety of immune reactions [8,12,13]. The direct role of cholinergic system in skin melanogenesis has been demonstrated.…”

Section: Introductionmentioning

confidence: 99%

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The UV‐induced uptake of melanosome by skin keratinocyte is triggered by α7 nicotinic acetylcholine receptor‐mediated phagocytosis

Guo

Dong

et al. 2022

The FEBS Journal

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The melanosome is an organelle that produces melanin for skin pigmentation, which is synthesized by epidermal melanocytes, subsequently transported and internalized by epidermal keratinocytes. Exposure to ultraviolet (UV) from sunlight radiation is a major stimulator of melanosome uptake by keratinocytes. Acetylcholine (ACh) is known to be released by keratinocytes under UV exposure, which regulates melanin production in melanocytes by participating in which has been named as ‘skin synapse’. Here, the role of cholinergic molecules, i.e. ACh and α7 nicotinic acetylcholine receptor (nAChR), in regulating melanosome uptake through phagocytosis by keratinocytes was illustrated. In cultured keratinocytes (HaCaT cells), the fluorescent beads at different sizes imitating melanosomes, or melanosomes, were phagocytosed under UV exposure. The UV‐induced phagocytosis in keratinocytes was markedly increased by applied ACh, an acetylcholinesterase (AChE) inhibitor or an α7 nAChR agonist. By contrast, the antagonist of α7 nAChR was able to fully block the UV‐induced phagocytosis, suggesting the role of α7 nAChR in this event. The intracellular Ca++ mobilization was triggered by UV exposure, accounting for the initiation of phagocytosis. The blockage of UV‐mediated Ca++ mobilization, triggered by BAPTA‐AM or α7 nAChR antagonist, resulted in a complete termination of phagocytosis. Besides, the phosphorylation of cofilin, as well as expression and activation of RhoA, accounting for phagocytosis was induced by UV exposure: the phosphorylation was blocked by BAPTA‐AM or α7 nAChR antagonist. The result suggests that the cholinergic system, especially α7 nAChR, is playing a regulatory role in modulating melanosome uptake in keratinocytes being induced by UV exposure.

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“…ACh binds to the acetylcholine receptor (AChR) and acetylcholinesterase (AChE) of melanocytes, resulting in the inhibition of the cAMP-dependent signaling pathway. Melanogenesis caused by solar light in melanocytes is suppressed by ACh and AChE inhibitors, indicating that the cholinergic mechanism plays a part in inhibiting melanogenesis [12,13].…”

Section: Acetylcholine Signaling Pathwaymentioning

confidence: 99%

Development of Pigmentation-Regulating Agents by Drug Repositioning

Jeong

Yoon

2021

IJMS

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Skin color is determined by the processes of melanin synthesis and distribution. Problems in various molecules or signaling pathways involved in melanin synthesis contribute to skin pigmentation defects. Several trials have been conducted on the production of pigmentation-regulating agents, and drug repositioning has emerged as a modern technique to identify new uses for existing drugs. Our research team has researched substances or drugs associated with pigmentation control and, as a result, nilotinib, sorafenib, and ICG-001 have been found to promote pigmentation, while 5-iodotubercidin inhibits pigmentation. Therefore, these substances or medications were suggested as potential therapeutics for pigmentation disorders by drug repositioning.

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Solar light induces expression of acetylcholinesterase in skin keratinocytes: Signalling mediated by activator protein 1 transcription factor

Cited by 10 publications

References 37 publications

Metabolic Profiling of Thymic Epithelial Tumors Hints to a Strong Warburg Effect, Glutaminolysis and Precarious Redox Homeostasis as Potential Therapeutic Targets

Metabolic Profiling of Thymic Epithelial Tumors Hints to a Strong Warburg Effect, Glutaminolysis and Precarious Redox Homeostasis as Potential Therapeutic Targets

The UV‐induced uptake of melanosome by skin keratinocyte is triggered by α7 nicotinic acetylcholine receptor‐mediated phagocytosis

Development of Pigmentation-Regulating Agents by Drug Repositioning

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