N-acetylcysteine (NAC) differentially affects arterial medial calcification and bone formation: The role of l-cysteine and hydrogen sulphide.

Autor: Bourne LE; Department of Comparative Biomedical Sciences, Royal Veterinary College, London, UK., Patel JJ; Department of Comparative Biomedical Sciences, Royal Veterinary College, London, UK., Davies BK; Department of Comparative Biomedical Sciences, Royal Veterinary College, London, UK., Neven E; Department of Biomedical Sciences, Laboratory of Pathophysiology, University of Antwerp, Antwerp, Belgium., Verhulst A; Department of Biomedical Sciences, Laboratory of Pathophysiology, University of Antwerp, Antwerp, Belgium., D'Haese PC; Department of Biomedical Sciences, Laboratory of Pathophysiology, University of Antwerp, Antwerp, Belgium., Wheeler-Jones CPD; Department of Comparative Biomedical Sciences, Royal Veterinary College, London, UK., Orriss IR; Department of Comparative Biomedical Sciences, Royal Veterinary College, London, UK.
Jazyk: angličtina
Zdroj: Journal of cellular physiology [J Cell Physiol] 2022 Jan; Vol. 237 (1), pp. 1070-1086. Date of Electronic Publication: 2021 Oct 17.
DOI: 10.1002/jcp.30605
Abstrakt: 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 2 S) 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 2 S mimicked those of NAC; however, the effects of H 2 S were much less efficacious than NAC and l-cysteine. Pharmacological inhibition of H 2 S-generating enzymes did not alter the actions of NAC or l-cysteine; endogenous production of H 2 S 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.
(© 2021 The Authors. Journal of Cellular Physiology published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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