2-Chloroadenosine but not adenosine induces apoptosis in rheumatoid fibroblasts independently of cell surface adenosine receptor signalling
Abstract
1. The apoptotic effect of adenosine and its analogues was studied in fibroblast-like synoviocytes derived from rheumatoid arthritis patients (RA-FLSs). Evoked cell death was quantitatively examined by assessing DNA fragmentation using an enzyme-liked immunosorbent assay and by measuring phosphatidylserine exposure through flow cytometric analysis of annexin V binding. 2. Exposing cells for 24 h to 2-chloroadenosine (2-CADO), a nonspecific, adenosine deaminase (ADA)-resistant, adenosine receptor (AdoR) agonist, induced DNA fragmentation, and thus apoptosis, in RA-FLSs at concentrations > or =50 microM. By contrast, incubation with adenosine for up to 72 h did not evoke DNA fragmentation, even in the presence of ADA inhibitor coformycin and nucleoside transporter inhibitor nitrobenzylmercaptopurin (NBMPR). Transcription of all four AdoR isoforms was detected in RA-FLSs; nevertheless selective AdoR agonists similarly failed to induce DNA fragmentation. 3. DNA fragmentation evoked by 2-CADO was inhibited by NBMPR and by 5'-iodotubercidin, an adenosine kinase inhibitor, but not by xanthine amine congener, an A(1) and A(2) receptor antagonist, or by selective AdoR antagonists. 4. The nonspecific caspase inhibitor benzyloxycarbonyl-V...Continue Reading
References
Classification of P2 purinoceptors. Not all G protein-coupled P2 purinoceptors can be classed as P2Y
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