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Zinc salicylate reduces airway smooth muscle cells remodelling by blocking mTOR and activating p21 (Waf1/Cip1) .
- Source :
-
The Journal of nutritional biochemistry [J Nutr Biochem] 2021 Mar; Vol. 89, pp. 108563. Date of Electronic Publication: 2020 Dec 14. - Publication Year :
- 2021
-
Abstract
- Asthma is characterized by chronic inflammation and tissue remodeling of the airways. Remodeling is resistant to pharmaceutical therapies. This study investigated the effect of zinc salicylate-methylsulfonylmethane (Zn-Sal-MSM) compared to zinc salicylate (Zn-Sal), or sodium salicylate (Na-Sal), or zinc chloride (ZnCl <subscript>2</subscript> ) on remodeling parameters of human airway smooth muscle cells (ASMC). Human ASMC obtained from asthma patients (n=7) and non-asthma controls (n=7) were treated with one of the reagents. Cell proliferation and viability was determined by direct cell counts and MTT assay. The expression of and phosphorylation proteins was determined by Western-blotting, ELISA, immunofluorescence, and mass spectrometry. Extracellular matrix deposition by ELISA. Zn-Sal-MSM, Zn-Sal and Na-Sal (0.1-100 µg/mL) significantly reduced PDGF-BB-induced proliferation in a concentration dependent manner, while ZnCl <subscript>2</subscript> was toxic. The reduced proliferation correlated with increased expression of the cell cycle inhibitor p21 <superscript>(Waf1/Cip1)</superscript> , and reduced activity of Akt, p70S6K, and Erk1/2. Zn-Sal-MSM, Zn-Sal, but not Na-Sal reduced the deposition of fibronectin and collagen type-I. Furthermore, Zn-Sal-MSM reduced the mitochondria specific COX4 expression. Mass spectrometry indicated that Zn-Sal-MSM modified the expression of several signaling proteins and zinc-dependent enzymes. In conclusion, Zn-Sal-MSM and Zn-Sal potentially prevent airway wall remodeling in asthma by inhibition of both the Erk1/2 and mTOR signaling pathways.<br /> (Copyright © 2020. Published by Elsevier Inc.)
- Subjects :
- Adult
Aged
Animals
Asthma metabolism
Asthma pathology
Cell Proliferation drug effects
Cell Survival drug effects
Cells, Cultured
Collagen Type I metabolism
Extracellular Matrix drug effects
Female
Fibronectins metabolism
Humans
MAP Kinase Signaling System drug effects
Male
Middle Aged
Ribosomal Protein S6 Kinases, 70-kDa metabolism
Signal Transduction drug effects
Airway Remodeling drug effects
Asthma drug therapy
Cyclin-Dependent Kinase Inhibitor p21 metabolism
Myocytes, Smooth Muscle drug effects
Salicylates pharmacology
TOR Serine-Threonine Kinases metabolism
Zinc pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-4847
- Volume :
- 89
- Database :
- MEDLINE
- Journal :
- The Journal of nutritional biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 33326841
- Full Text :
- https://doi.org/10.1016/j.jnutbio.2020.108563