在2型糖尿病中,通过线粒体Ca2+调节光滑肌肉细胞的增殖
Olha M Koval1, Emily K Nguyen1, Dylan J Mittauer1
1Abboud Cardiovascular Research Center, Division of Cardiovascular Medicine, Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
International journal of molecular sciences
|August 26, 2023
概括
2型糖尿病通过破坏处理和线粒体功能,导致血管光滑肌肉细胞过度增殖. 针对这些途径可能会降低疾病风险.
科学领域:
- 心血管生物学 心血管生物学
- 线粒体医学 线粒体医学
- 糖尿病研究 糖尿病研究
背景情况:
- 2型糖尿病 (T2D) 增加了动脉样硬化血管疾病的风险,部分原因是血管光滑肌细胞 (VSMC) 的过度增殖.
- 线粒体功能障碍和细胞内 (Ca2+) 水平的改变与T2D病理生理学有关.
研究的目的:
- 研究线粒体功能障碍和Ca2+失调在T2D背景下VSMC增殖中的作用.
- 探索调节线粒体Ca2+处理和相关信号通路的治疗潜力.
主要方法:
- 从正常血糖和类似T2D的小鼠中分离出VSMC.
- 通过基因操纵 (mtCaMKII抑制) 和药理学药物 (mPTP抑制剂) 抑制了线粒体Ca2+吸收.
- 评估了细胞质和线粒体Ca2+水平,增殖标志物 (Erk1/2) 和对生长因子 (PDGF) 的反应.
主要成果:
- T2D VSMCs显示扩散增加,基线细胞质Ca2+ ([Ca2+]细胞) 升高,线粒体Ca2+吸收减少,Ca2+处理受损.
- 抑制线粒体Ca2+进入或mPTP开放减少了T2DVSMC的扩散.
- 在T2DVSMC中改变的Ca2+处理促进了Erk1/2过活化,这是扩散的关键驱动因素.
结论:
- 改变Ca2+处理,由线粒体功能障碍加剧,是T2D中过度VSMC增殖的关键驱动因素.
- 针对线粒体Ca2+调节和下游Ca2+依赖的信号通路,为T2D相关的血管并发症提供了潜在的治疗策略.
相关概念视频
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
Smooth Muscle Contraction
3.2K
Smooth muscle contraction is a complex process vital for various bodily functions, from maintaining blood vessel tension to facilitating the movement of food through the digestive tract. Unlike striated muscles, smooth muscle contraction begins more slowly and lasts longer.
The onset of contraction is triggered by an increase in calcium ions within the sarcoplasm, similar to the process in striated muscle. However, smooth muscles have a relatively smaller reservoir of the sarcoplasmic...
The onset of contraction is triggered by an increase in calcium ions within the sarcoplasm, similar to the process in striated muscle. However, smooth muscles have a relatively smaller reservoir of the sarcoplasmic...
3.2K
Diabetes Mellitus: Type 2 and Gestational
2.5K
Type 2 diabetes, characterized by insulin resistance, arises when the insulin receptors on cells lose responsiveness to insulin, diminishing the cell's capacity to take up glucose, resulting in elevated blood glucose levels. To receive a diagnosis of Type 2 diabetes, a series of blood glucose tests are necessary to assess whether the blood glucose falls within normal parameters. If the result is out of the normal range, a patient may be diagnosed as prediabetic or diabetic, depending on the...
2.5K
PI3K/mTOR/AKT Signaling Pathway
3.7K
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...
3.7K
Mitochondrial Membranes
11.6K
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
11.6K
Electron Transport Chain: Complex I and II
14.5K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
14.5K


