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

@article{citeulike:2355676, abstract = {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. 10.1152/ajprenal.00440.2006}, author = {Solini, Anna and Santini, Eleonora and Chimenti, Daniele and Chiozzi, Paola and Pratesi, Federico and Cuccato, Sabina and Falzoni, Simonetta and Lupi, Roberto and Ferrannini, Ele and Pugliese, Giuseppe and Virgilio, Francesco D. }, citeulike-article-id = {2355676}, doi = {http://dx.doi.org/10.1152/ajprenal.00440.2006}, journal = {Am J Physiol Renal Physiol}, month = {May}, number = {5}, pages = {F1537--1547}, posted-at = {2008-02-09 04:30:05}, priority = {2}, title = {Multiple P2X receptors are involved in the modulation of apoptosis in human mesangial cells: evidence for a role of P2X4}, url = {http://dx.doi.org/10.1152/ajprenal.00440.2006}, volume = {292}, year = {2007} }

TY - JOUR ID - citeulike:2355676 L3 - citeulike-article-id:2355676 TI - Multiple P2X receptors are involved in the modulation of apoptosis in human mesangial cells: evidence for a role of P2X4 JF - Am J Physiol Renal Physiol VL - 292 IS - 5 SP - F1537 EP - 1547 N2 - 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. 10.1152/ajprenal.00440.2006 AU - Solini, Anna AU - Santini, Eleonora AU - Chimenti, Daniele AU - Chiozzi, Paola AU - Pratesi, Federico AU - Cuccato, Sabina AU - Falzoni, Simonetta AU - Lupi, Roberto AU - Ferrannini, Ele AU - Pugliese, Giuseppe AU - Virgilio, Francesco PY - 2007/05/01/ UR - http://dx.doi.org/10.1152/ajprenal.00440.2006 ER -