在慢性压力下,Actn2缺陷通过ERK酸化加速H9c2缩
Kang Wang1, Ye Wang1, Hua Wan2
1Department of Forensic Medicine, Nanjing Medical University, Nanjing, 211166, China.
Genes & genomics
|July 11, 2024
概括
失去ACTN2功能通过ERK信号加速慢性压力下的心脏缩. 使用ERK抑制剂或IBUDILAST的药物干预在体外显示出逆转这些效应的潜力.
科学领域:
- 心血管生物学 心血管生物学
- 分子心脏病学分子心脏病学
- 细胞应激反应的应激反应
背景情况:
- ACTN2中的突变与DCM和HCM等心肌病,以及心脏突然死亡有关.
- ACTN2调节了瘤细胞Z盘组织,但其在慢性压力下心肌病中的作用尚不清楚.
研究的目的:
- 为了研究ACTN2失调和慢性压力下心肌病之间的关系,使用德甲治疗.
- 探索ACTN2在心脏缩中的作用背后的分子机制.
主要方法:
- 使用MEGA 11和Polyphen-2对ACTN2突变的分析.
- 在体外抑制ACTN2在H9c2细胞与siRNA在甲治疗下.
- 转录组分析和Westernblotting用于识别受影响的途径.
- 在体外测试ERK抑制剂和ibudilast.
主要成果:
- 在甲下,ACTN2抑制降低了的摄取量,增加了H9c2细胞的缩.
- 在ACTN2受抑制细胞中观察到高过量分子生物标志物.
- 抑制ACTN2过度激活了MAPK/ERK通路;ERK抑制剂部分逆转了缩.
结论:
- 在慢性压力下,ACTN2功能的丧失通过ERK信号加速H9c2细胞缩.
- 伊布迪拉斯特被确定为一种潜在的治疗剂,用于逆转细胞增大在体外.
相关概念视频
cAMP-dependent Protein Kinase Pathways
6.3K
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,...
6.3K
PI3K/mTOR/AKT Signaling Pathway
3.5K
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...
3.5K
mTOR Signaling and Cancer Progression
3.8K
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...
3.8K
Tension Response at Adherens Junctions
2.6K
The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
2.6K
Enzyme-linked Receptors
77.9K
Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
77.9K
Actin Polymerization and Cell Motility
5.2K
Actin is a family of globular proteins that are highly abundant in eukaryotic cells. It makes up approximately 1-5% of total cell protein concentration. Actin monomers polymerize to form a complex network of polarized filaments, the actin cytoskeleton, that plays a crucial role in many cellular processes, including cell motility, division, endocytosis, and metastasis of cancer cells.
Actin cytoskeleton dynamics can produce pushing, pulling, and resistance forces that help the cell to migrate....
Actin cytoskeleton dynamics can produce pushing, pulling, and resistance forces that help the cell to migrate....
5.2K


