PMID- 19923798 OWN - NLM STAT- MEDLINE DCOM- 20100607 LR - 20161125 IS - 1421-9670 (Electronic) IS - 0250-8095 (Linking) VI - 31 IP - 2 DP - 2010 TI - JNK/ATF2 pathway is involved in iodinated contrast media-induced apoptosis. PG - 125-33 LID - 10.1159/000259899 [doi] AB - BACKGROUND/AIMS: Notably, activating transcriptional factor 2 (ATF2), a histone-modification gene, is involved in oxidative stress-induced apoptosis. The aim of this study was to clarify the role of ATF2 in contrast media-induced nephropathy. METHODS: Human embryonic kidney 293T cells were treated with four different contrast media:ionic high-osmolar diatrizoate; ionic low-osmolar iothalamate; non-ionic low-osmolar iohexol, and non-ionic iso-osmolar iodixanol. The mRNA expression of ATF2 was determined by real-time PCR. Short interfering RNA was used to knock down ATF2 mRNA expression. Phosphorylation of ATF2 was measured by Western blotting. Wistar rats were administered either diatrizoate or a normal saline injection. Apoptosis in kidney tubular cells was determined by the presence of positive TUNEL stain. RESULTS: Diatrizoate, iodixanol and iothalamate, but not iohexol, induced the expression of ATF2 mRNA and phosphorylation of ATF2 in 293T cells in a time-dependent manner. More apoptotic cells were in diatrizoate-treated kidney cells than in the saline injection group (p < 0.00001). Cell death was significantly increased by knockdown ATF2 expression in the presence of diatrizoate, indicating a protective role of ATF2 in contrast media-induced apoptosis. CONCLUSIONS: Differential activation of ATF2 by different contrast media provides a new insight into the mechanism and prevention of contrast-induced nephropathy. CI - Copyright (c) 2009 S. Karger AG, Basel. FAU - Lee, Hsiang-Chun AU - Lee HC AD - Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100 Tz-You 1st Road, Kaohsiung, Taiwan, ROC. FAU - Sheu, Sheng-Hsiung AU - Sheu SH FAU - Yen, Hsueh-Wei AU - Yen HW FAU - Lai, Wen-Ter AU - Lai WT FAU - Chang, Jan-Gowth AU - Chang JG LA - eng PT - Journal Article DEP - 20091117 PL - Switzerland TA - Am J Nephrol JT - American journal of nephrology JID - 8109361 RN - 0 (ATF2 protein, human) RN - 0 (Activating Transcription Factor 2) RN - 0 (Contrast Media) RN - 0 (Tetrazolium Salts) RN - 0 (Thiazoles) RN - 117-96-4 (Diatrizoate) RN - 9679TC07X4 (Iodine) RN - EC 2.7.12.2 (MAP Kinase Kinase 4) RN - EUY85H477I (thiazolyl blue) SB - IM MH - Activating Transcription Factor 2/*metabolism MH - Animals MH - *Apoptosis MH - Cell Survival MH - Contrast Media/*pharmacology MH - Diatrizoate/pharmacology MH - Humans MH - In Situ Nick-End Labeling MH - Iodine/*pharmacology MH - Kidney/metabolism/pathology MH - MAP Kinase Kinase 4/*metabolism MH - Models, Biological MH - Phosphorylation MH - Rats MH - Reverse Transcriptase Polymerase Chain Reaction MH - Tetrazolium Salts/pharmacology MH - Thiazoles/pharmacology EDAT- 2009/11/20 06:00 MHDA- 2010/06/09 06:00 CRDT- 2009/11/20 06:00 PHST- 2009/04/15 00:00 [received] PHST- 2009/10/12 00:00 [accepted] PHST- 2009/11/20 06:00 [entrez] PHST- 2009/11/20 06:00 [pubmed] PHST- 2010/06/09 06:00 [medline] AID - 000259899 [pii] AID - 10.1159/000259899 [doi] PST - ppublish SO - Am J Nephrol. 2010;31(2):125-33. doi: 10.1159/000259899. Epub 2009 Nov 17.