双A通过控制 G2/M 阶段细胞周期,亡信号传递,MAPK 途径和转录因子相关的 MMP 调节来调节膀细胞的反应
Jun-Hui Song1, Byungdoo Hwang1, Solbi Park1
1Department of Food and Nutrition, Chung-Ang University, Anseong, Republic of Korea.
Journal of biochemical and molecular toxicology
|February 19, 2024
概括
双甲 (BPA) 暴露会触发细胞死亡,并通过细胞亡和细胞循环停止停止膀细胞的生长. BPA还通过抑制关键的转录因子和酶,损害了膀细胞的迁移和入侵.
科学领域:
- 毒理学 毒理学 毒理学
- 细胞生物学 细胞生物学
- 内分泌学 在内分泌学.
背景情况:
- 双A (BPA) 是一种在聚碳酸塑料中普遍存在的内分泌干扰化学物质.
- 人类尿样中BPA的存在引发了对其对膀的影响的公共卫生问题.
研究的目的:
- 研究BPA对人类膀细胞的不良影响背后的分子机制.
- 阐明BPA如何影响膀细胞的细胞生长,循环,亡和迁移.
主要方法:
- 用于体外研究的人类膀细胞系 (BdFC和T24).
- 分析了亡途径 (内在和外在) 和细胞循环调节 (G2/M停止).
- 评估了BPA对转录因子 (AP-1,NF-κB) 和矩阵金属蛋白酶 (MMP-2,MMP-9) 以及MAPK酸化的影响.
主要成果:
- 在人类膀细胞中,BPA诱导了外在和内在的亡以及G2/M细胞周期的停止.
- 通过破坏ATM-CHK1/CHK2-CDC25c-CDC2信号通路,BPA抑制了细胞生长.
- BPA降低了AP-1和NF-κB的结合活性,从而通过MMP-2和MMP-9的失活减少了迁移和入侵,其中涉及MAPK酸化.
结论:
- BPA通过多个分子通路对人类膀细胞产生细胞毒性作用.
- 这项研究揭示了BPA诱导的膀细胞损伤的新型机制,包括细胞亡,细胞循环停止和迁移受损.
- 这些发现凸显了BPA暴露对膀健康的潜在风险.
更多相关视频
11:02Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
Published on: October 30, 2013
21.3K
07:08Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants
Published on: March 6, 2018
6.1K
相关概念视频
Interactions Between Signaling Pathways
6.3K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.3K
Negative Regulator Molecules
35.4K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.4K
DNA Damage can Stall the Cell Cycle
9.2K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.2K
MAPK Signaling Cascades
5.5K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.5K
Amplifying Signals via Enzymatic Cascade
8.5K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
8.5K
The Intrinsic Apoptotic Pathway
6.5K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.5K
