title: The role of protein kinase CK2 in cyclosporine-induced nephropathy in rats.
abstract: OBJECTIVE
  Protein kinase casein kinase II (PKCK2) has multiple, overlapping roles in induction of apoptosis. Apoptosis can be a common pathway of renal injury caused by a nephrotoxic drug or an injury. We evaluated the role of PKCK2 in cyclosporine (CsA)-induced nephropathy in rats by inhibiting PKCK2 with emodin.
  
  
  METHODS
  Male Sprague-Dawley rats fed a low-sodium diet were divided into four treatment groups: control (0.9% saline injection), CsA (15 mg/kg/d subcutaneously), CsA + emodin (CsA plus emodin 20 mg/kg/d subcutaneously), and emodin only. The expression levels of apoptosis-associated factors and of PKCK2 were examined by Western blot analysis.
  
  
  RESULTS
  Overexpression of PKCK2 noted with CsA treatment was prevented by emodin, a low-molecular-weight PKCK2 inhibitor, which dampend drug-induced up-regulation phosphorylated p53 and activation of caspases 3, 7, and 8. In addition, emodin prevented increased Bax/Bcl-2 ratio induced by CsA. Emodin prevented up-regulation of PKCK2 by CsA treatment, suggesting that its apoptotic-preventing activity was mediated via PKCK2.
  
  
  CONCLUSIONS
  Our findings indicated that PKCK2 may play a role in apoptotic injury associated with CsA-induced nephropathy in rats.
authors.affiliation: Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea.
authors.forename: Y K
authors.initials: YK
authors.lastname: Son
authors.forename: S M
authors.initials: SM
authors.lastname: Lee
authors.forename: W S
authors.initials: WS
authors.lastname: An
authors.forename: K H
authors.initials: KH
authors.lastname: Kim
authors.forename: S H
authors.initials: SH
authors.lastname: Rha
authors.forename: J H
authors.initials: JH
authors.lastname: Rho
authors.forename: S E
authors.initials: SE
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D047390:Casein Kinase II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D016572:Cyclosporine; D004039:Diet, Sodium-Restricted; D004195:Disease Models, Animal; D004642:Emodin / Q000494:pharmacology; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control; D008297:Male; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D047428:Protein Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D016572:Cyclosporine; D047390:Casein Kinase II; C505410:Casp3 protein, rat; C505528:Casp8 protein, rat; D053148:Caspase 3; D053179:Caspase 7; D053181:Caspase 8; D004642:Emodin