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Norisoboldine induces apoptosis of fibroblast-like synoviocytes from adjuvant-induced arthritis rats.
- Source :
-
International immunopharmacology [Int Immunopharmacol] 2014 May; Vol. 20 (1), pp. 110-6. Date of Electronic Publication: 2014 Mar 06. - Publication Year :
- 2014
-
Abstract
- Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by pronounced synovial inflammation and hyperplasia, in which there may be an imbalance between the growth and death of fibroblast-like synoviocytes (FLS). Norisoboldine (NOR), the main active constituent in the alkaloid fraction isolated from Radix Linderae, was previously demonstrated to alleviate arthritis severity in experimental RA. This study aimed to evaluate the effects of NOR on proliferation and apoptosis of FLS from adjuvant-induced arthritis (AIA) rats to elucidate the mechanism of its inhibitory effect on inflammatory synovial hyperplasia in RA. Our results indicated that NOR exhibited a pro-apoptotic effect on AIA FLS but only slightly affected cell proliferation and the cell cycle. Following treatment with NOR for 24h, the activation of caspase 3 and caspase 9 and the cleavage of poly (ADP-ribose) polymerase (PARP) in AIA FLS were observed; however, caspase 8 remained unaffected. Meanwhile, a flow cytometric assay revealed that NOR significantly increased the percentage of apoptotic cells, causing the loss of the depolarized mitochondrial membrane potential and the release of cytochrome C. The expression of Bax and Bcl-2 was also regulated by NOR treatment. Additionally, the expression of p53 protein was up-regulated by NOR, and pretreatment with PFT-α, a p53 specific inhibitor, reversed the increase in FLS apoptosis caused by NOR. These findings indicated that NOR-induced apoptosis in AIA FLS is achieved via a mitochondrial-dependent pathway, which may be mediated by promoting the release of cytochrome C and by regulating the expression of Bax and Bcl-2 proteins, and p53 might also be required for NOR-induced apoptosis in AIA FLS.<br /> (Copyright © 2014 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Caspase 3 metabolism
Caspase 9 metabolism
Cell Cycle drug effects
Cell Proliferation drug effects
Cell Survival drug effects
Cytochromes c metabolism
Male
Membrane Potential, Mitochondrial drug effects
Poly(ADP-ribose) Polymerases metabolism
Proto-Oncogene Proteins c-bcl-2 metabolism
Rats, Sprague-Dawley
Tumor Suppressor Protein p53 metabolism
bcl-2-Associated X Protein metabolism
Alkaloids pharmacology
Apoptosis drug effects
Arthritis, Experimental metabolism
Synovial Membrane cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1705
- Volume :
- 20
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- International immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 24613208
- Full Text :
- https://doi.org/10.1016/j.intimp.2014.02.023