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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Restoration of skeletal muscle homeostasis by hydrogen sulfide during hyperhomocysteinemia-mediated oxidative/ER stress condition
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Restoration of skeletal muscle homeostasis by hydrogen sulfide during hyperhomocysteinemia-mediated oxidative/ER stress condition

机译:高管抑制氧化/ ER应力条件下硫化氢硫化氢恢复骨骼肌稳态

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摘要

Elevated homocysteine (Hcy), i.e., hyperhomocysteinemia (HHcy), causes skeletal muscle myopathy. Among many cellular and metabolic alterations caused by HHcy, oxidative and endoplasmic reticulum (ER) stress are considered the major ones; however, the precise molecular mechanism(s) in this process is unclear. Nevertheless, there is no treatment option available to treat HHcy-mediated muscle injury. Hydrogen sulfide (H2S) is increasingly recognized as a potent anti-oxidant, anti-apoptotic/necrotic/pyroptotic, and anti-inflammatory compound and also has been shown to improve angiogenesis during ischemic injury. Patients with CBS mutation produce less H2S, making them vulnerable to Hcy-mediated cellular damage. Many studies have reported bidirectional regulation of ER stress in apoptosis through JNK activation and concomitant attenuation of cell proliferation and protein synthesis via PI3K/AKT axis. Whether H2S mitigates these detrimental effects of HHcy on muscle remains unexplored. In this review, we discuss molecular mechanisms of HHcy-mediated oxidative/ER stress responses, apoptosis, angiogenesis, and atrophic changes in skeletal muscle and how H2S can restore skeletal muscle homeostasis during HHcy condition. This review also highlights the molecular mechanisms on how H2S could be developed as a clinically relevant therapeutic option for chronic conditions that are aggravated by HHcy.
机译:升高的同型半胱氨酸(HCY),即高管囊肿(HHCY),导致骨骼肌肌病。在由HHCY,氧化和内质网(ER)应激引起的许多细胞和代谢改变被认为是主要的细胞和内质网(ER)胁迫;然而,该方法中的精确分子机制尚不清楚。然而,没有可治疗的治疗方法可以治疗HHCy介导的肌肉损伤。硫化氢(H 2 S)越来越普及为有效的抗氧化剂,抗凋亡/坏死/糊化孔和抗炎化合物,并且还显示出在缺血性损伤期间改善血管生成。患有CBS突变的患者产生较少的H2S,使其容易受到HCY介导的细胞损伤。许多研究报告了通过PI3K / AKT轴通过JNK激活和伴随细胞增殖和蛋白质合成的凋亡中ER应激的双向调节。 H2S是否减轻了Hhcy对肌肉的这些不利影响仍然是未开发的。在该综述中,我们讨论了Hhcy介导的氧化/ ER应激反应,凋亡,血管生成和骨骼肌的萎缩变化的分子机制以及H2S在HHCY条件下如何恢复骨骼肌稳态。该综述还突出了如何将H2S开发为HHCY加重的慢性条件的临床相关治疗选择的分子机制。

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