PMID- 11170791 OWN - NLM STAT- MEDLINE DCOM- 20010322 LR - 20161124 IS - 0014-4800 (Print) IS - 0014-4800 (Linking) VI - 70 IP - 1 DP - 2001 Feb TI - Puromycin aminonucleoside induces glomerular epithelial cell apoptosis. PG - 54-64 AB - 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 microg/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 microg/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. FAU - Sanwal, V AU - Sanwal V AD - Molecular Biology and Experimental Pathology Section, Long Island Jewish Medical Center and North Shore University Hospital, New York, New York 11040, USA. FAU - Pandya, M AU - Pandya M FAU - Bhaskaran, M AU - Bhaskaran M FAU - Franki, N AU - Franki N FAU - Reddy, K AU - Reddy K FAU - Ding, G AU - Ding G FAU - Kapasi, A AU - Kapasi A FAU - Valderrama, E AU - Valderrama E FAU - Singhal, P C AU - Singhal PC LA - eng GR - R01 DA 12111/DA/NIDA NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - Netherlands TA - Exp Mol Pathol JT - Experimental and molecular pathology JID - 0370711 RN - 0 (Free Radical Scavengers) RN - 1CC1JFE158 (Dactinomycin) RN - 58-60-6 (Puromycin Aminonucleoside) RN - 8P30PMD17W (1,3-dimethylthiourea) RN - 9007-49-2 (DNA) RN - EC 1.11.1.6 (Catalase) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - GYV9AM2QAG (Thiourea) SB - IM MH - Animals MH - Apoptosis/*drug effects MH - Catalase/pharmacology MH - Cells, Cultured MH - DNA/drug effects MH - DNA Fragmentation/drug effects MH - Dactinomycin/pharmacology MH - Disease Models, Animal MH - Dose-Response Relationship, Drug MH - Electrophoresis, Agar Gel MH - Epithelial Cells/drug effects/pathology MH - Free Radical Scavengers/pharmacology MH - Humans MH - In Situ Nick-End Labeling MH - Kidney Glomerulus/*drug effects/pathology MH - Puromycin Aminonucleoside/*toxicity MH - Rats MH - Rats, Sprague-Dawley MH - Superoxide Dismutase/pharmacology MH - Thiourea/*analogs & derivatives/pharmacology EDAT- 2001/02/15 11:00 MHDA- 2001/03/27 10:01 CRDT- 2001/02/15 11:00 PHST- 2001/02/15 11:00 [pubmed] PHST- 2001/03/27 10:01 [medline] PHST- 2001/02/15 11:00 [entrez] AID - S0014-4800(00)92345-1 [pii] AID - 10.1006/exmp.2000.2345 [doi] PST - ppublish SO - Exp Mol Pathol. 2001 Feb;70(1):54-64. doi: 10.1006/exmp.2000.2345.