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This Article Full Text Full Text (PDF) All Versions of this Article: 292/5/F1537    most recent 00440.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Solini, A. Articles by Virgilio, F. D. Search for Related Content PubMed PubMed Citation Articles by Solini, A. Articles by Virgilio, F. D.

Multiple P2X receptors are involved in the modulation of apoptosis in human mesangial cells: evidence for a role of P2X₄

¹Department of Internal Medicine, ²Section of Diabetes and Metabolic Diseases, University of Pisa, Pisa; ³Department of Experimental and Diagnostic Medicine, University of Ferrara; ⁴Department of Clinical Sciences, "La Sapienza" University, Rome; and ⁵Interdisciplinary Center for the Study of Inflammation, University of Ferrara, Ferrara, Italy

Submitted 6 November 2006 ; accepted in final form 21 January 2007

Apoptosis, a normal event in renal tissue homeostasis, has been considered as a major mechanism for either resolution of glomerular hypercellularity in glomerulonephritis or loss of cellularity and progression to glomerulosclerosis in chronic renal disease. This study was aimed at investigating the role of extracellular ATP (eATP) in mediating apoptosis in human mesangial cells (HMC) and identifying the subtype(s) of purinergic receptors involved. eATP, but not uridin-5'-triphosphate (UTP), caused dose-dependent modifications of cellular morphology, as assessed by contrast-phase microscopy, and late apoptosis, as measured by Annexin V/propidium iodide-based flow cytometry and caspase-3 activation. Both phenomena were prevented by the P2X antagonist oxidized-ATP. 2', 3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate (BzATP) was less effective than ATP, whereas 1[N,O-bis (5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl] -4-phenylpiperazine (KN62), a selective inhibitor of human P2X₇, prevented morphological changes but potentiated apoptosis induced by BzATP. P2X₇ was barely expressed in HMC and showed a relatively scarce functional activity, as assessed by monitoring nucleotide-induced intracellular calcium surge and plasma membrane depolarization by Fura-2/AM and bis[1,3-diethylthiobarbiturate]trimethineoxonal uptake, respectively. These data indicated a negligible role of P2X₇ in eATP-mediated apoptosis and pointed to the involvement of other P2X receptor(s). Molecular and inhibitor studies suggested a main role for P2X₄ receptor in nucleotide-induced apoptosis in HMC, indicating a relevant role for purinergic signaling in regulating death rate in these cells.

extracellular ATP; purinergic receptors; mesangium