Acetazolamide protects rat articular chondrocytes from IL-1β-induced apoptosis by inhibiting the activation of NF-κB signal pathway.
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY(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-1 beta (IL-1 beta)-induced apoptosis, a classic in vitro model of chondrocyte apoptosis. AZ treatment could inhibit IL-1 beta-induced apoptosis, evidenced by increasing cell viability, relieving apoptotic nuclear morphology, decreasing apoptosis rates, and restoring mitochondrial membrane potential. Additionally, AZ reversed IL-1 beta-induced decrease of Bcl-2 protein and reduced IL-1 beta-induced increases of Bax and caspase 3 protein, accompanied by inhibiting I kappa B alpha degradation and phosphorylation in cytoplasm, reducing NF-kappa B p65 protein level in nucleus and preventing NF-kappa B p65 translocation from cytoplasm to nucleus. In conclusion, our findings indicated that AZ could effectively attenuate IL-1 beta-induced chondrocyte apoptosis mediated by regulating the protein levels of apoptosis-related genes and inhibiting the activation of NF-kappa B signal pathway, suggesting that AZ might be of potential clinical interest in RA treatment.
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Key words
acetazolamide,aquaporin1,articular chondrocytes,apoptosis,rheumatoid arthritis,NF-kappa B,IL-1 beta
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