JNK/ATF2 pathway is involved in iodinated contrast media-induced apoptosis.
OBJECTIVE
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.
Lee
Hsiang-Chun
HC
Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100 Tz-You 1st Road, Kaohsiung, Taiwan, ROC.
Sheu
Sheng-Hsiung
SH
Yen
Hsueh-Wei
HW
Lai
Wen-Ter
WT
Chang
Jan-Gowth
JG
D051698:Activating Transcription Factor 2 / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D003287:Contrast Media / Q000494:pharmacology*; D003973:Diatrizoate / Q000494:pharmacology; D006801:Humans; D020287:In Situ Nick-End Labeling; D007455:Iodine / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D008954:Models, Biological; D010766:Phosphorylation; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D003287:Contrast Media; D013778:Tetrazolium Salts; D013844:Thiazoles; D003973:Diatrizoate; D007455:Iodine; D048670:MAP Kinase Kinase 4; C022616:thiazolyl blue