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NADPH oxidase inhibitor inhibits methylglyoxal‐induced podocyte apoptosis (LB729)
Author(s) -
Kim Young Sook,
Jung Dong Ho,
Pyun BoJeong,
Choi SoJin Choi,
Kim Jin Sook Kim
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb729
Subject(s) - nadph oxidase , methylglyoxal , podocyte , kinase , p38 mitogen activated protein kinases , mapk/erk pathway , chemistry , apoptosis , reactive oxygen species , microbiology and biotechnology , protein kinase a , biology , biochemistry , endocrinology , kidney , enzyme , proteinuria
Methylglyoxal (MG) is one of uremic toxins produced by glycolysis that may results in diabetic nephropathy. In this study, we investigated the effect and mechanism of MG on apoptosis in podocytes. Conditionally immortalized podocytes for differentiation were induced by culturing the cells at 37°C for 13~15 days and treated MG with various concentration (0, 50,100, 200, 400 μM). Our data show that MG induced a decrease in cell viability in a dose‐dependent manner and increased formation of dichlorofluorescein (DCF)‐sensitive intracellular reactive oxygen species (ROS). This enhanced ROS formation was significantly reduced by NADPH oxidase inhibitor (DPI, 5 μM). Furthermore, MG treatment induced apoptosis in podocyte and NADPH oxidase inhibitor inhibited MG‐induced podocytes apoptosis via cleavage inhibition of poly (ADP‐ribose) polymerase (PARP). MG treatment also induced phosphorylation of extracellular‐regulated kinase 1/2 (ERK1/2), p38 mitogen‐activated protein kinases (MAPKs), protein kinase C‐alpha and ‐ delta/zeta, and phosphoinositide‐3 kinase (PI3K). Pretreatment with these inhibitors inhibited MG‐induced phosphorylation of these molecules in podocytes. These results suggest that MG‐induced apoptosis may be mediated by signaling of ERK, MAPK, PKC and PI3K in podocyte. Grant Funding Source : KIOM13040