title: Activation level of JNK and Akt/ERK signaling pathways determinates extent of DNA damage in the liver of diabetic rats.
abstract: OBJECTIVE
  Diabetes-related oxidative stress conditions lead to progressive tissue damage and disfunctionality. Mechanisms underlying liver pathophysiology during diabetes are not fully understood. The aim of this study was to find relationship between diabetes-related DNA damage in the rat liver and activities of prosurvival signaling pathways.
  
  
  METHODS
  Effect of diabetes was analyzed two (development stage) and eight weeks (stable diabetes) after single intraperitoneal injection of streptozotocin. Extent of DNA damage, analysed by comet assay, was corelated with oxidative status (plasma level of ROS, liver antioxidant capacity) and activity/abundance of kinases (Akt, p38, ERK1, JNK, JAK) and transcription factors NF-κB p65 and STAT3.
  
  
  RESULTS
  Significant DNA damage in development stage is accompanied by elevated plasma levels of O(2)(-) and H(2)O(2), decreased activities of CAT, MnSOD, and GST in the liver and increased activation of proapoptotic JNK signal pathway. Lower DNA damage in stable diabetes, is accompanied by elevated plasma level of O(2)(-), restored antioxidative liver enzyme activity, decreased activation of JNK and increased activation of prosurvival Akt and ERK signal pathways.
  
  
  CONCLUSIONS
  These findings indicate that level of DNA damage in diabetic liver depends on the extent of oxidative stress, antioxidant activity and balance between JNK and Akt/ERK signal pathways activation .
authors.affiliation: Department of Molecular Biology, Institute for Biological Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Vesna
authors.initials: V
authors.lastname: Martinović
authors.forename: Ilijana
authors.initials: I
authors.lastname: Grigorov
authors.forename: Desanka
authors.initials: D
authors.lastname: Bogojević
authors.forename: Anja
authors.initials: A
authors.lastname: Petrović
authors.forename: Sofija
authors.initials: S
authors.lastname: Jovanović
authors.forename: Mirka
authors.initials: M
authors.lastname: Ilić
authors.forename: Svetlana
authors.initials: S
authors.lastname: Ivanović Matić
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism; D020552:Comet Assay; D004249:DNA Damage; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology; D005982:Glutathione Transferase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000097:blood; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D026082:Singlet Oxygen / Q000097:blood; D013482:Superoxide Dismutase / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D050796:STAT3 Transcription Factor; D051996:Transcription Factor RelA; D026082:Singlet Oxygen; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D048031:JNK Mitogen-Activated Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases