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Acetazolamide protects rat articular chondrocytes from IL-1β-induced apoptosis by inhibiting the activation of NF-κB signal pathway.
- Source :
-
Canadian journal of physiology and pharmacology [Can J Physiol Pharmacol] 2018 Nov; Vol. 96 (11), pp. 1104-1111. Date of Electronic Publication: 2018 Aug 01. - Publication Year :
- 2018
-
Abstract
- Because the excessive apoptosis of articular chondrocytes contributes to extracellular matrix (ECM) loss and cartilage damage in rheumatoid arthritis (RA), inhibiting chondrocyte apoptosis might be a promising strategy for RA. Aquaporin1 (AQP1) is overexpressed in RA cartilage and synovial tissues, and play a vital pathogenic role in RA development. Particularly, we previously reported that acetazolamide (AZ) as an AQP1 inhibitor suppressed secondary inflammation and promoted ECM production in cartilage of adjuvant-induced arthritis rats. Here, we investigated the antiapoptotic effect of AZ on interleukin-1β (IL-1β)-induced apoptosis, a classic in vitro model of chondrocyte apoptosis. AZ treatment could inhibit IL-1β-induced apoptosis, evidenced by increasing cell viability, relieving apoptotic nuclear morphology, decreasing apoptosis rates, and restoring mitochondrial membrane potential. Additionally, AZ reversed IL-1β-induced decrease of Bcl-2 protein and reduced IL-1β-induced increases of Bax and caspase 3 protein, accompanied by inhibiting IκBα degradation and phosphorylation in cytoplasm, reducing NF-κB p65 protein level in nucleus and preventing NF-κB p65 translocation from cytoplasm to nucleus. In conclusion, our findings indicated that AZ could effectively attenuate IL-1β-induced chondrocyte apoptosis mediated by regulating the protein levels of apoptosis-related genes and inhibiting the activation of NF-κB signal pathway, suggesting that AZ might be of potential clinical interest in RA treatment.
- Subjects :
- Animals
Cartilage, Articular cytology
Cells, Cultured
Chondrocytes metabolism
Interleukin-1beta metabolism
Primary Cell Culture
Rats
Rats, Sprague-Dawley
Transcription Factor RelA metabolism
Acetazolamide pharmacology
Apoptosis drug effects
Carbonic Anhydrase Inhibitors pharmacology
Chondrocytes drug effects
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1205-7541
- Volume :
- 96
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Canadian journal of physiology and pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 30067070
- Full Text :
- https://doi.org/10.1139/cjpp-2018-0334