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首页> 外文期刊>Journal of cellular physiology. >N-acetylcysteine (NAC) differentially affects arterial medial calcification and bone formation: The role of L-cysteine and hydrogen sulphide
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N-acetylcysteine (NAC) differentially affects arterial medial calcification and bone formation: The role of L-cysteine and hydrogen sulphide

机译：防治(NAC)不同影响动脉内钙化和骨形成:半胱氨酸和硫化氢的角色

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摘要

Arterial medial calcification (AMC) is the deposition of calcium phosphate in the arteries. AMC is widely thought to share similarities with physiological bone formation; however, emerging evidence suggests several key differences between these processes. N-acetylcysteine (NAC) displays antioxidant properties and can generate hydrogen sulphide (H_2S) and glutathione (GSH) from its deacetylation to l-cysteine. This study found that NAC exerts divergent effects in vitro, increasing osteoblast differentiation and bone formation by up to 5.5-fold but reducing vascular smooth muscle cell (VSMC) calcification and cell death by up to 80%. In vivo, NAC reduced AMC in a site-specific manner by 25% but had no effect on the bone. The actions of L-cysteine and H_2S mimicked those of NAC; however, the effects of H_2S were much less efficacious than NAC and L-cysteine. Pharmacological inhibition of H_2S-generating enzymes did not alter the actions of NAC or L-cysteine; endogenous production of H_2S was also unaffected. In contrast, NAC and L-cysteine increased GSH levels in calcifying VSMCs and osteoblasts by up to 3-fold. This suggests that the beneficial actions of NAC are likely to be mediated via the breakdown of L-cysteine and the subsequent GSH generation. Together, these data show that while the molecular mechanisms driving the actions of NAC appear similar, the downstream effects on cell function differ significantly between osteoblasts and calcifying VSMCs. The ability of NAC to exert these differential actions further supports the notion that there are differences between the development of pathological AMC and physiological bone formation. NAC could represent a therapeutic option for treating AMC without exerting negative effects on bone.
机译：动脉内侧钙化(AMC)沉积磷酸钙的动脉。AMC被广泛认为有相似之处生理骨形成;证据表明几个关键的区别这些过程。抗氧化性能,可以产生氢气硫化物(硫化氢)、谷胱甘肽(GSH)的半胱氨酸脱乙酰作用。在体外,NAC施加不同的影响,增加成骨细胞分化和骨形成了5.5倍,但减少血管平滑肌细胞(VSMC)钙化和细胞死亡达80%。但没有影响特定站点的方式25%骨头。模仿的南汽;检测比南汽和更有效半胱氨酸。H_2S-generating酶没有改变的行动南汽或半胱氨酸;检测也未受到影响。半胱氨酸钙化增加谷胱甘肽的水平VSMCs和成骨细胞的三倍。表明,南汽的有益行为通过故障可能是介导半胱氨酸和随后的谷胱甘肽的一代。这些数据显示,虽然分子机制推动南汽的行动出现类似,下游对细胞的影响函数成骨细胞之间也有明显的差异和钙化VSMCs。这些微分操作进一步的支持认为有差异病理AMC和生理的发展骨形成。选择治疗AMC没有施加负面的对骨骼的影响。

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