蛋白酸酶6通过抑制Akt/mTOR信号传递来保护肝细胞免受内细胞网膜和氧化应激的影响
Nobuyuki Fujiwara1, Ikki Mitsui2, Ryoichi Tsunedomi3
1Laboratory of Drug Discovery and Pharmacology, Faculty of Veterinary Medicine, Okayama University of Science, Ehime, Japan.
Biochemical and biophysical research communications
|February 18, 2026
概括
蛋白酸酶6 (PP6) 抑制了Akt/mTOR信号传递,以保持肝脏的健康. 在正常情况下,肝细胞中PP6的损失会导致肝损伤和线粒体功能障碍.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 蛋白酸酶6 (PP6) 是一种氨酸/氨酸酸酶,涉及各种细胞功能.
- 以前的研究通过mTORC1信号将PP6与代谢功能障碍相关的脂肪肝炎 (MASH) 联系起来.
- 在生理条件下,PP6在维持肝脏平衡中的作用尚不清楚.
研究的目的:
- 研究PP6在肝细胞功能和肝脏平衡中的生理作用.
- 阐明PP6调节肝脏健康的分子机制.
主要方法:
- 产生肝细胞特异性Ppp6c缺陷 (PP6 HKO) 的小鼠.
- 分析肝脏病理,血清标志物和细胞压力指标.
- 肝细胞的转录和超结构分析.
- 对Akt/mTOR和ERK信号通路的研究.
主要成果:
- PP6 HKO小鼠表现出自发性肝脏异常,包括肝壮病,损伤标志物,亡和炎症.
- 转录组学揭示了被抑制的线粒体氧化酸化和丰富的炎症和亡途径.
- PP6的损失导致持续的Akt/mTOR通路过活化,导致线粒体功能障碍和细胞应激.
- 在缺乏PP6的肝细胞中观察到受损的线粒体晶状体和内等质网膜扩张.
结论:
- 在生理条件下,PP6对于维持肝细胞平衡至关重要.
- PP6通过抑制Akt/mTOR信号通路而起作用.
- PP6的失调会通过线粒体功能障碍和细胞压力导致肝损伤.
相关概念视频
PI3K/mTOR/AKT Signaling Pathway
5.8K
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...
5.8K
Protein Kinases and Phosphatases
15.3K
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
15.3K
Protein Kinases and Phosphatases
4.5K
4.5K
The JAK-STAT Signaling Pathway
13.2K
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...
13.2K
mTOR Signaling and Cancer Progression
4.9K
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...
4.9K
Amplifying Signals via Enzymatic Cascade
18.7K
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...
18.7K


