通过PI3K/Akt路径激活,ATF3作为一个分子关联链,将铁亡调节与萨科佩尼亚病原体联系起来
Zhi Chen1, Dingxiang Hu2, Chengjian Wu1
1Department of Orthopaedics Sports Injury Division, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, China.
Experimental gerontology
|July 16, 2025
概括
这项研究表明,ATF3 (激活转录因子3) 通过PI3K/Akt通路调节铁亡,在肉症中起着关键作用. 抑制ATF3可能为与年龄相关的肌肉损失提供治疗策略.
科学领域:
- 肌肉生物学和衰老研究研究.
- 铁灭菌的细胞机制
- 年龄相关疾病的分子基础.
背景情况:
- 标志着肌肉损失和肌肉衰弱的萨尔科佩尼亚,其原因不明确,治疗方法有限.
- 铁,一种依赖于铁的细胞死亡,越来越多地涉及到肉症的进展.
- 萨科佩尼亚中铁灭菌的特定分子调节剂仍然未被定义.
研究的目的:
- 为了研究铁和肉类的相互作用.
- 为了确定这个过程的关键分子调节者.
- 为了阐明底层的分子机制.
主要方法:
- 使用了体内 (SAMP8小鼠) 和体内 (C2C12神经细胞) 模型.
- 评估了sarcopenia表型,铁沉积和基因表达.
- 通过生物信息学分析确定ATF3为枢纽基因.
- 验证了ATF3在铁和PI3K/Akt信号传递中的作用.
主要成果:
- 年龄较大的小鼠显示了sarcopenia特征,铁的增加和ATF3表达的减少.
- 肌细胞中ATF3过度表达降低了铁亡标志物 (ROS,MDA) 和缩.
- ATF3激活了PI3K/Akt通路,这对其抑制铁灭的作用至关重要.
结论:
- ATF3 起到铁和肉症之间的关键分子联系的作用.
- PI3K/Akt通路是ATF3介导的调节萨尔科佩尼亚中铁的核心.
- 准ATF3可能代表了对萨尔科佩尼亚的新疗法.
相关概念视频
PI3K/mTOR/AKT Signaling Pathway
4.0K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
4.0K
mTOR Signaling and Cancer Progression
3.9K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.9K
Necrosis
4.9K
Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
4.9K
The JAK-STAT Signaling Pathway
9.3K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
9.3K
The Unfolded Protein Response
5.1K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
5.1K


