OBJECTIVE: To evaluate the role of the MAPK subtypes (p38MAPK, ERK and JNK) in ANG II-induced apoptosis of cultured human podocytes. METHODS: The cultured podocytes were incubated in media containing either vehicle, SB202190(5 micromol/L, an inhibitor of p38MAPK), PD98059 (1 micromol/L, an inhibitor of ERK), SP600125 (5 micromol/L, an inhibitor of JNK), ANG II (10(-8)mol/L) with or without SB202190 PD98059 and SP600125 for 18 hours; the cells were assayed for apoptosis by morphologic staining with H-33342 and propidium iodide and DNA fragmentation assays; the cell proteins were probed for phosphorylated MAPKs to determine the activation of specific MAPK subtypes. RESULTS: ANG II promoted podocyte apoptosis in a time- and dose-dependent manner; ANG II stimulated p38MAPK, but inhibited JNK; SB202190 inhibited both ANG II-induced podocyte apoptosis and p38MAPK phosphorylation; Inhibition of ERK by PD98059 had no effect on ANG II-induced cell apoptosis. CONCLUSION: ANG II-induced apoptosis through stimulation of p38MAPK and inhibition of JNK in human podocytes.
OBJECTIVE: To evaluate the role of the MAPK subtypes (p38MAPK, ERK and JNK) in ANG II-induced apoptosis of cultured human podocytes. METHODS: The cultured podocytes were incubated in media containing either vehicle, SB202190(5 micromol/L, an inhibitor of p38MAPK), PD98059 (1 micromol/L, an inhibitor of ERK), SP600125 (5 micromol/L, an inhibitor of JNK), ANG II (10(-8)mol/L) with or without SB202190PD98059 and SP600125 for 18 hours; the cells were assayed for apoptosis by morphologic staining with H-33342 and propidium iodide and DNA fragmentation assays; the cell proteins were probed for phosphorylated MAPKs to determine the activation of specific MAPK subtypes. RESULTS:ANG II promoted podocyte apoptosis in a time- and dose-dependent manner; ANG II stimulated p38MAPK, but inhibited JNK; SB202190 inhibited both ANG II-induced podocyte apoptosis and p38MAPK phosphorylation; Inhibition of ERK by PD98059 had no effect on ANG II-induced cell apoptosis. CONCLUSION:ANG II-induced apoptosis through stimulation of p38MAPK and inhibition of JNK in human podocytes.
Authors: Mamon Dey; Aleksander Baldys; Dezmond B Sumter; Pal Göoz; Louis M Luttrell; John R Raymond; Monika Göoz Journal: J Pharmacol Exp Ther Date: 2010-06-21 Impact factor: 4.030