Regulation of nicotinic acetylcholine receptor α3 subtype in adipose tissue dysfunction

Bai, Xiaoqing; Ju, Haibing; Gao, Li; Xiong, Yong; Dai, Rong; Huang, Xiang‐Zhong; Yang, Cui

doi:10.1016/j.prostaglandins.2019.04.001

Cited by 6 publications

(3 citation statements)

References 17 publications

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“…Nicotine contributes to tumorigenesis through the stimulation of nAChRs in HNSC, which is consistent with our GSEA results in curated gene sets (39). Consistent research showed CHRNB4 knockdown led to reduced proliferation and propensity to form colonies in lung cancer cells (40). What is more, our in vitro experiments showed that knockdown of CHRNB4 inhibited the growth of ESCC cells and the result of western blot validated that the potential mechanism was the Akt/mTOR and ERK1/2/mTOR signaling pathway, which play an essential role in ESCC progression.…”

Section: Discussionsupporting

confidence: 89%

Identification of CHRNB4 as a Diagnostic/Prognostic Indicator and Therapeutic Target in Human Esophageal Squamous Cell Carcinoma

Liu

Dong

et al. 2020

Front. Oncol.

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Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignant tumors and there is a lack of biomarkers for ESCC diagnosis and prognosis. Family subunits of cholinergic nicotinic receptor genes (CHRNs) are involved in smoking behavior and tumor cell proliferation. Previous researches have shown similar molecular features and pathogenic mechanisms among ESCC, head and neck squamous cell carcinoma (HNSC), and lung squamous cell carcinoma (LUSC). Using edgeR, three mutual differentially expressed genes of CHRNs were found to be significantly upregulated at the mRNA level in ESCC, LUSC, and HNSC compared to matched normal tissues. Kaplan–Meier survival analysis showed that high expression of CHRNB4 was associated with unfavorable prognosis in ESCC and HNSC. The specific expression analysis revealed that CHRNB4 is highly expressed selectively in squamous cell carcinomas compared to adenocarcinoma. Cox proportional hazards regression analysis was performed to find that just the single gene CHRNB4 has enough independent prognostic ability, with the area under curve surpassing the tumor-node-metastasis (TNM) staging-based model, the most commonly used model in clinical application in ESCC. In addition, an effective prognostic nomogram was established combining the TNM stage, gender of patients, and expression of CHRNB4 for ESCC patients, revealing an excellent prognostic ability when compared to the model of CHRNB4 alone or TNM. Gene Set Enrichment Analysis results suggested that the expression of CHRNB4 was associated with cancer-related pathways, such as the mTOR pathway. Cell Counting Kit-8, cloning formation assay, and western blot proved that CHRNB4 knockdown can inhibit the proliferation of ESCC cells via the Akt/mTOR and ERK1/2/mTOR pathways, which might facilitate the prolonged survival of patients. Furthermore, we conducted structure-based molecular docking, and potential modulators against CHRNB4 were screened from FDA approved drugs. These findings suggested that CHRNB4 specifically expressed in SCCs, and may serve as a promising biomarker for diagnosis and prognosis prediction, and it can even become a therapeutic target of ESCC patients.

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Section: Discussionsupporting

confidence: 89%

Identification of CHRNB4 as a Diagnostic/Prognostic Indicator and Therapeutic Target in Human Esophageal Squamous Cell Carcinoma

Liu

Dong

et al. 2020

Front. Oncol.

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“…TNF-alpha (tumor necrosis factor) production from adipocytes was lowered by activating nAChRs, indicating that nAChRs may alleviate adipose inflammation. Bai et al hypothesized that in high-fat diet-fed ApoE/mice with 3-nAChR blocked and in IL-6-stimulated adipocytes with α3-nAChR gene silenced, the productions of leptin, resistin, triglyceride, cholesterol, and low-density lipoprotein were significantly increased, but the generations of adiponectin and high-density lipoprotein were significantly deceased [40]. Meanwhile, inflammatory cytokine production was significantly increased.…”

Section: Adipose Tissue Dysfunction (Obesity-related Diseases)mentioning

confidence: 99%

Role of Acetylcholine in Chronic Diseases

Mohan¹,

Kaushik²,

Arora³

2023

Acetylcholine - Recent Advances and New Perspectives

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The complex and extensive network of brain signals plays a vital role in maintaining physiological mechanisms and homeostasis. Acetylcholine, a chief neurotransmitter of the parasympathetic nervous system, is an important component of the cholinergic system along with cholinergic receptors, acetylcholinesterase, and choline acetyltransferase. It is responsible for mediating cell-to-cell communication and regulates various peripheral and non-neuronal cholinergic signals. Any alteration in the levels of acetylcholine leads to chronic diseases. Chronic diseases, the leading causes of disability, require continuing health care, medical attention, and potential therapeutics. This chapter will cover a brief overview of acetylcholine including its synthesis and degradation, the cholinergic system, and the influence of acetylcholine on different chronic diseases including neurological complications, metabolic disorders, cardiac diseases, and immune disorders. Moreover, the mechanistic approach of acetylcholine in different diseases and the therapies for recovering the levels of acetylcholine will be reviewed in this chapter. Further, this will illustrate the acetylcholine interaction with various cells implicated in the diseases. The insights on agonists and antagonists of acetylcholine and different targets of cholinergic receptors that could help to design better strategies to control these chronic diseases will also be provided.

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“…Recent studies have also found that JAK2-STAT3 signaling pathway is involved in cognitive improvement [20][21][22][23], and JAK2-STAT3 signaling pathway is proposed to play a role in the activation of α 3 -, α 5 -and α 7 -nAChRs [24][25][26][27][28]. There seems a relationship between α 4 β 2 nAChRs and JAK2-STAT3 as well [29,30].…”

Section: Introductionmentioning

confidence: 99%

Nicotine Activating α4β2 Nicotinic Acetylcholine Receptors to Suppress Neuroinflammation via JAK2-STAT3 Signaling Pathway in Ischemic Rats and Inflammatory Cells

et al. 2022

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Nicotine plays a role in inhibiting the in ammatory factors, which contributes to improving cognitive impairment by activating α 4 β 2 nAChRs in ischemic rats, but the underling mechanism has not been fully elucidated. Janus tyrosine kinase 2-signal transducer and activator of transcription 3 (JAK2-STAT3) signaling pathway is involved in cognitive improvement, and there seems a relationship between nAChRs and JAK2-STAT3 as well. This study was designed to investigate the role of JAK2-STAT3 signaling pathway in nicotine-mediated anti-in ammation effect. Nicotine, DHβE (the most potent competitive antagonist of α 4 β 2 nAChRs) and AG490 (a speci c JAK2-STAT3 blocker) were adopted for intervention treatment in ischemic rats and HEK-293T-hα 4 β 2 cells. Morris Water Maze (MWM) test and 2-[18F]-A-85380 PET imaging were performed to detect the cognition and α 4 β 2 nAChRs in ischemic rats. The results demonstrated that nicotine intervention increased the density of α 4 β 2 nAChRs and improved cognitive impairment, but this effect would be blocked by AG490, while receptors were still upregulated.Essentially, when JAK2-STAT3 signaling pathway was blocked, nicotine could only upregulate the expression of α 4 β 2 nAChRs, but not improve the cognitive function. The results were further con rmed by PCR and Western blot analysis. The cell experiments also showed that nicotine could reduce in ammatory factors stimulated by LPS and upregulate the expression of pJAK2 and pSTAT3 in HEK-293T-hα 4 β 2 cells, while AG490 and DHβE reversed nicotine's effect. In summary, our work indicated that JAK2-STAT3 signaling pathway played an important role in nicotine-induced cognitive improvement by up-regulating α 4 β 2 nAChRs in ischemic rats.

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Regulation of nicotinic acetylcholine receptor α3 subtype in adipose tissue dysfunction

Cited by 6 publications

References 17 publications

Identification of CHRNB4 as a Diagnostic/Prognostic Indicator and Therapeutic Target in Human Esophageal Squamous Cell Carcinoma

Identification of CHRNB4 as a Diagnostic/Prognostic Indicator and Therapeutic Target in Human Esophageal Squamous Cell Carcinoma

Role of Acetylcholine in Chronic Diseases

Nicotine Activating α4β2 Nicotinic Acetylcholine Receptors to Suppress Neuroinflammation via JAK2-STAT3 Signaling Pathway in Ischemic Rats and Inflammatory Cells

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