Activation Level of JNK and Akt/ERK Signaling Pathways Determinates Extent of DNA Damage in the Liver of Diabetic Rats

Cellular Physiology and Biochemistry

关键词: Rat Liver;    Diabetes;    Oxidative Stress;    DNA Damage;    Signaling Pathways;   

DOI  :  10.1159/000341452

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Aims 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-ĸB p65 and STAT3. Results Significant DNA damage in development stage is accompanied by elevated plasma levels of O₂^-and H₂O₂, 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 O₂^-, restored antioxidative liver enzyme activity, decreased activation of JNK and increased activation of prosurvival Akt and ERK signal pathways. Conclusion 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..

【 授权许可】

CC BY-NC-ND