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Inhibitory effect of mabuterol on proliferation of rat ASMCs induced by PDGF-BB via regulating [Ca 2+ ]i and mitochondrial fission/fusion.
- Source :
-
Chemico-biological interactions [Chem Biol Interact] 2019 Jul 01; Vol. 307, pp. 63-72. Date of Electronic Publication: 2019 Apr 19. - Publication Year :
- 2019
-
Abstract
- This study is aimed to investigate whether Mabuterol (Mab) inhibits proliferation of airway smooth muscle cells (ASMCs) induced by platelet-derived growth factor BB (PDGF-BB) and how far it is related to mitochondrial fission/fusion and intracellular calcium if it comes into play. To explore the mechanism of Mab's antagonizing the proliferation, Mdivi-1, DRP1 inhibitor, which has an inhibitory effect on mitochondrial fission, is used to compare with Mab. Cell viability was measured by either MTT or CCK-8. The inhibitory effect of Mab on S phase of ASM cell cycle induced by PDGF-BB was analyzed by flow cytometry (FCM). Fluo-3/AM, Ca <superscript>2+</superscript> fluorescent probe, was used to detect Ca <superscript>2+</superscript> fluorescence intensity by inverted microscope and flow cytometry. The gene expression of Drp-1 and Mfn-2 was observed with Real time PCR and the proteins of Drp-1, Mfn-2, PCNA and cyclin D1 were assessed by Western Blot. Mab and Mdivi-1 both suppressed the proliferation induced by PDGF-BB. The results from inverted microscope and flow cytometry showed that Mab inhibited [Ca <superscript>2+</superscript> ]i in rat ASMCs induced by PDGF-BB. Cell cycle concept map illustrated that Mab significantly controlled the S phase of ASM cell cycle induced by PDGF-BB. As a consequence, Real time PCR and Western blot revealed the fact that Mab decreased the expression of Drp-1 mRNA and protein, and promoted the expression of Mfn-2 mRNA and protein. These findings suggested that Mab placed restrictions on the proliferation of rat ASMCs induced by PDGF-BB and the mechanism might be associated with the intracellular calcium inhibited and the mitochondrial fission/fusion regulated by Mab.<br /> (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Cell Cycle Checkpoints drug effects
Cells, Cultured
Clenbuterol pharmacology
Cyclin D1 genetics
Cyclin D1 metabolism
Down-Regulation drug effects
Female
Male
Membrane Potential, Mitochondrial drug effects
Muscle, Smooth, Vascular cytology
Muscle, Smooth, Vascular drug effects
Muscle, Smooth, Vascular metabolism
Quinazolinones pharmacology
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species metabolism
Becaplermin pharmacology
Calcium metabolism
Cell Proliferation drug effects
Clenbuterol analogs & derivatives
Mitochondrial Dynamics drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7786
- Volume :
- 307
- Database :
- MEDLINE
- Journal :
- Chemico-biological interactions
- Publication Type :
- Academic Journal
- Accession number :
- 31009640
- Full Text :
- https://doi.org/10.1016/j.cbi.2019.04.023