蛋白质氨酸N-甲基转移酶4激活有助于葡萄糖诱导的骨肌肉缩
Pawan Kumar1,2, Farah Gulzar1, Nikita Chhikara1,2
1Division of Biochemistry and Structural Biology, CSIR-Central Drug Research Institute, Lucknow, India.
概括
蛋白质氨酸N-甲基转移酶4 (PRMT4) 通过破坏胰岛素信号和激活蛋白质降解来驱动糖尿病的骨肌肉缩. 抑制PRMT4可以治疗糖尿病患者的肌肉消耗.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 代谢疾病 代谢疾病
背景情况:
- 蛋白质氨酸N-甲基转移酶4 (PRMT4) 调节骨肌肉的可塑性,但其在糖尿病肌肉缩中的作用尚不清楚.
- 骨肌肉代谢平衡对于整体健康至关重要,特别是在糖尿病等疾病中.
研究的目的:
- 研究PRMT4在高葡萄糖引起的骨肌肉缩中的作用.
- 阐明PRMT4在糖尿病肌肉缩中的功能背后的分子机制.
主要方法:
- 使用的L6髓管暴露在高葡萄糖条件下.
- 使用药理抑制和siRNA介导的PRMT4.4的下调.
- 评估了mRNA和蛋白质水平,胰岛素信号传递和蛋白质降解途径 (ubiquitin-proteasome和自).
主要成果:
- 高葡萄糖增加了PRMT4表达,并诱导了L6髓管中的缩特征.
- 抑制PRMT4抑制/下调抑制高葡萄糖诱导的缩.
- 激活PRMT4导致ADMA升高,破坏了胰岛素信号传递,并激活了无素-蛋白酶体通路,而不是自.
- 蛋白质酶活性释放氨基酸,以PRMT4依赖的方式激活mTOR信号.
结论:
- PRMT4是高葡萄糖诱导的骨肌肉缩的关键调节者.
- PRMT4通过破坏胰岛素信号和促进蛋白质降解通过无素-蛋白酶体路径来调解缩.
- PRMT4代表了管理糖尿病相关的骨肌缩的潜在治疗标.
相关概念视频
01:22PI3K/mTOR/AKT Signaling Pathway
5.3K
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...
5.3K
01:25cAMP-dependent Protein Kinase Pathways
8.3K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
8.3K
03:03mTOR Signaling and Cancer Progression
4.6K
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...
4.6K
01:24Muscle Recovery and Fatigue
4.0K
Muscle fatigue refers to the decline in a muscle's ability to maintain the force of contraction after prolonged activity. It primarily stems from changes within muscle fibers. Even before experiencing muscle fatigue, one may feel tired and have the urge to stop the activity. This response, known as central fatigue, occurs due to changes in the central nervous system, namely the brain and spinal cord. While there is no single mechanism that induces fatigue, it may serve as a protective...
4.0K
01:26Cross-bridge Cycle
122.2K
As muscle contracts, the overlap between the thin and thick filaments increases, decreasing the length of the sarcomere—the contractile unit of the muscle—using energy in the form of ATP. At the molecular level, this is a cyclic, multistep process that involves binding and hydrolysis of ATP, and movement of actin by myosin.
122.2K
01:21Overview of Protein Metabolism
3.6K
Proteins are broken down into amino acids during digestion. Unlike fats and carbohydrates, which are stored for later use, proteins are not. Instead, amino acids are either used to produce ATP through oxidation or contribute to the creation of new proteins for the growth and repair of the body. Any surplus amino acids from the diet are converted into glucose or triglycerides rather than excreted.
Amino acids play various roles in the body once they are absorbed into cells. They are restructured...
Amino acids play various roles in the body once they are absorbed into cells. They are restructured...
3.6K