title: Role of ERK1/2 and JNK phosphorylation in iodine contrast agent-induced apoptosis in diabetic rat kidneys.
abstract: BACKGROUND
  The risk of contrast-induced acute kidney injury (CIAKI) is significantly increased in patients with diabetes mellitus. This study aimed to investigate molecular mechanisms of contrast media-induced apoptosis in diabetic rat kidneys, especially the involvement of ERK1/2 and JNK signal pathways.
  
  
  METHODS
  Diabetic Sprague-Dawley rats were induced by intraperitoneal injection of streptozotocin. Ten weeks later the normal and diabetic rats were administered high-osmolar contrast media (HOCM; meglumine diatrizoate) or normal saline (10 mL/kg) injection for 2 consecutive days. At 24 h after the operation, the rats were sacrificed, the blood samples were collected for examining serum creatinine and the kidneys were collected for determining the expression of caspase-3 by immunohistochemistry and the expression of Bcl-2, Bax, upstream signal molecule p-JNK, and p-ERK1/2 by western blotting.
  
  
  RESULTS
  The serum creatinine was significantly increased in diabetes + contrast media group (DC group) after operation compared with in the diabetic group (D group; 103.89 ± 9.01 μmol/L vs. 71.52 ± 7.03 μmol/L, p < 0.05). While creatinine clearance rate (Ccr) was significantly decreased in DC group after operation (1.49 ± 0.33 mL/min vs. 2.60 ± 0.54 mL/min, p < 0.05). Especially, in the diabetic kidney, the expression of caspase-3 was also significantly increased after intravenous injection of HOCM compared with normal saline. The expression level of upstream signal molecule p-JNK protein was apparently increased, but p-ERK1/2 protein was significantly decreased (both p < 0.05).
  
  
  CONCLUSIONS
  The ionic HOCM-induced renal cells apoptosis in diabetic rats through activating the caspase-3 apoptotic pathway, which might be mediated by upstream MAPK (inhibiting p-ERK1/2 expression and promoting p-JNK expression) signal pathways.
authors.affiliation: a Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology , Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University , Tianjin , China and.
authors.forename: Zhanquan
authors.initials: Z
authors.lastname: Jiao
authors.affiliation: a Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology , Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University , Tianjin , China and.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: b Department of Cardiology , Tianjin Third Central Hospital , Tianjin , China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: a Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology , Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University , Tianjin , China and.
authors.forename: Tong
authors.initials: T
authors.lastname: Liu
authors.affiliation: a Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology , Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University , Tianjin , China and.
authors.forename: Kangyin
authors.initials: K
authors.lastname: Chen
authors.affiliation: a Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology , Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University , Tianjin , China and.
authors.forename: Guangping
authors.initials: G
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D003287:Contrast Media / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced; D004195:Disease Models, Animal; D007455:Iodine / Q000009:adverse effects*; D007668:Kidney / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000235:genetics*; D008297:Male; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin / Q000008:administration & dosage
chemical_list: D003287:Contrast Media; D013311:Streptozocin; D007455:Iodine; D003404:Creatinine; C505410:Casp3 protein, rat; D053148:Caspase 3
keywords: Apoptosis; ERK1/2; JNK; contrast-induced acute kidney injury; diabetes mellitus