尼古丁乙胆受体通过调节STAT5和Akt通路来调节乳腺上皮细胞中的氨酸分泌和氨酸表达
Ken Kobayashi1, Yuki Yasui1, Tamaki Uehara1
1Laboratory of Cell and Tissue Biology, Research Faculty of Agriculture, Hokkaido University, North 9, West 9, 060-8589, Sapporo, Japan.
Biochemical and biophysical research communications
|May 18, 2025
概括
吸烟产生的尼古丁通过干扰乳腺细胞中的乙胆/尼古丁乙胆受体 (ACh/nAChR) 途径来破坏母乳生产. 这会影响母乳养母亲的牛奶量和成分.
科学领域:
- 哺乳期生物学 哺乳期生物学
- 细胞信号传输 细胞信号传输
- 毒理学 毒理学 毒理学
背景情况:
- 哺乳期吸烟会减少母乳的体积,改变母乳的成分.
- 尼古丁转移到母乳中,可能会影响乳腺上皮细胞 (MEC).
- 尼古丁对MEC的牛奶产量和紧接口 (TJs) 产生影响的确切机制尚未完全理解.
研究的目的:
- 研究尼古丁性乙胆受体 (nAChRs) 和乙胆 (ACh) 在调节MEC中的牛奶产量和TJs中的作用.
- 阐明尼古丁对MEC的影响中涉及的信号通路.
主要方法:
- 利用一种能够产生牛奶和TJ形成的MEC体外培养模型.
- 使用的nAChR激动剂 (Br-PBTC,NS3861),ACH,乙胆酶抑制剂 (donepezil) 和nAChR对抗剂 (α-conotoxin PIA).
- 评估了素分泌,克劳丁-4表达,以及STAT5和Akt信号分子的激活状态.
主要成果:
- nAChR激动剂抑制了素分泌和增加了克劳丁-4,同时禁用了STAT5和Akt.
- 单独的ACH并没有影响素分泌,克劳丁表达或STAT5/Akt激活.
- 乙胆酶抑制和nAChR对抗效应模仿了对素分泌和信号通路的抑制作用.
结论:
- MECs通过乙胆/nAChR轴调节牛奶产量和TJ形成.
- 尼古丁通过破坏这一关键的ACH/nAChR信号通路,对MEC的牛奶产量产生不利影响.
- 这些发现突出了尼古丁对哺乳期负面影响的新机制.
相关概念视频
Calmodulin-dependent Signaling
5.0K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.0K
Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.0K
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.0K
Cholinergic Receptors: Muscarinic
1.6K
The pharmacological actions of acetylcholine are elicited via its binding to two families of cholinergic receptors or cholinoceptors, namely, muscarinic and nicotinic receptors. Muscarinic receptors are G protein-coupled receptors and have five subtypes, M1–M5. All mAChR subtypes are activated by acetylcholine and blocked by the antagonist, atropine.
The subtypes M1, M3, and M5 couple with the Gq subunit and activate the phospholipase C (PLC) activity, mobilizing intracellular Ca2+....
The subtypes M1, M3, and M5 couple with the Gq subunit and activate the phospholipase C (PLC) activity, mobilizing intracellular Ca2+....
1.6K
Notch Signaling Pathway
4.1K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.1K
Cadherins in Tissue Organization
2.9K
The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
Cell Sorting During Development
Cell sorting plays an...
2.9K
Overview of Secretory Vesicles
7.4K
Secretory vesicles, also known as dense core vesicles (DCVs), are membrane-bound vesicles that transport secretory proteins, such as hormones or neurotransmitters. Regulated secretory vesicles transport proteins from the trans-Golgi network to the exterior of the cell. Proteins present in regulated secretory vesicles are required to be rapidly exocytosed in large amounts upon a specific stimulus.
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
7.4K


