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Mesangial Cell Apoptosis Induced by Stimulation of the Adenosine A3 Receptor
  1. Pu Duann,
  2. Teh-Yuan Ho,
  3. Bijal D. Desai,
  4. Toros Kapoian,
  5. Daniel S. Cowen,
  6. Elias A. Lianos
  1. From the Department of Medicine (P.D., T.H., B.D., T.K., E.A.L.), Nephrology Division, and the Department of Psychiatry (D.S.C.), Robert Wood Johnson Medical School, New Brunswick, NJ. Supported by a Paul Teschan Research Grant (to T.K.) and by a Kidney and Urology Foundation of America grant (to B.D.) and a National Institute of Mental Health (NIMH) Grant MH60100 (to D.S.C.).
  1. Address correspondence to: Elias A. Lianos, MD, PhD, UMDNJ-Robert Wood Johnson Medical School, 1 Robert Wood Johnson Place, PO Box 19 - MEB 412, New Brunswick, NJ 0903-0019; e-mail: lianosea{at}

Signaling and Apoptotic Events


Mesangial cell apoptosis has been proposed as a means of resolution of glomerular hypercellularity in proliferative forms of glomerular disease. We previously demonstrated that adenosine causes mesangial cell apoptosis by stimulating the A3-type adenosine receptor. This is a G protein-coupled receptor shown to activate kinases involved in apoptotic signaling. In this work, we assessed changes in phosphorylation of the mitogen-activated protein kinase extracellular signal-regulated kinase (ERK)1/2 and in levels of specific pro- and antiapoptotic proteins following exposure of mesangial cells to the A3 adenosine receptor agonist N(6)-(3-iodobenzyl)-adenosine-5′-N-methyluronamide (IB-MECA). Cultured mesangial cells were incubated with IB-MECA for 30 minutes and 6, 24, and 48 hours. IB-MECA was used at a concentration (30 μM) that induces a reproducible degree of mesangial cell apoptosis. Changes in ERK1/2 phosphorylation and in protein levels of Bcl-2, Bax, and caspase 3 were assessed by Western blot analysis. IB-MECA markedly increased phosphorylation of ERK1/2. This effect peaked at 5 minutes, dissipated by 20 minutes, and was abolished by the inhibitor of ERK phosphorylation, compound U0126, in a dose-dependent manner. This inhibitor had no effect on the extent of IB-MECA-induced apoptosis. Bcl-2 levels progressively declined, whereas those of Bax and activated caspase 3 increased. These observations indicate that stimulation of the A3-type adenosine receptor causes mesangial cell apoptosis via mechanisms independent of ERK activation. The observations also point to an imbalance in the expression of antiapoptotic (Bcl-2) and proapoptotic (Bax, caspase 3) proteins as a potential mechanism underlying adenosine-induced mesangial cell apoptosis.

  • Mesangial cell
  • apoptosis
  • adenosine A3 receptor

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