Puromycin aminonucleoside induces glomerular epithelial cell apoptosis

被引:48
作者
Sanwal, V [1 ]
Pandya, M
Bhaskaran, M
Franki, N
Reddy, K
Ding, GH
Kapasi, A
Valderrama, E
Singhal, PC
机构
[1] Long Isl Jewish Med Ctr, Div Kidney Dis & Hypertens, Mol Biol & Expt Pathol Sect, New York, NY 11040 USA
[2] N Shore Univ Hosp, New York, NY 11040 USA
关键词
free radical scavengers; actinomycin D; necrosis; glomerulosclerosis; mesangium;
D O I
10.1006/exmp.2000.2345
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Glomerular epithelial cell (GEC) injury has been considered to play an important role in puromycin aminonucleoside (PAN)-induced nephrosis. We studied the effect of PAN on rat as well as human GEC apoptosis. Morphogic evaluation of GEC apoptosis and necrosis was carried out by staining with H-33342 and propidium iodide. GEC apoptosis was further confirmed by DNA fragmentation assay (by both agarose gel electrophoresis and end-labeling). To determine the dose- and time-response effect of PAN, GECs were treated with variable concentrations of PAN (10 to 500 mug/ml) for variable time periods (6 to 48 h). To determine the role of gene synthesis, we studied the effect of actinomycin D (a transcriptional inhibitor) on PAN-induced GEC apoptosis. To determine the role of free radicals, we evaluated the effect of superoxide dismutase (SOD), dimethylthiourea (DMTU), and catalase on PAN-induced GEC apoptosis. PAN induced GEC apoptosis in a dose- and time-dependent manner. PAN at a high concentration (PAN, 100 mug/ml) also induced a moderate degree of GEC necrosis. In DNA fragmentation assays PAN-treated GECs showed the classic ladder pattern. PAN-induced GEC apoptosis was partly attenuated with free radical scavengers, such as SOD, DMTU, and catalase. In addition, actinomycin D attenuated PAN-induced GEC apoptosis. PAN induces GEC apoptosis, which may be mediated through the generation of reactive oxygen species. (C) 2001 Academic Press.
引用
收藏
页码:54 / 64
页数:11
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