TXNIP mediated the oxidative stress response in glomerular mesangial cells partially through AMPK pathway.
Biomedicine & Pharmacotherapy(2018)
Abstract
Background: Thioredoxin-interacting protein (TXNIP) plays an important role in the development of diabetic nephropathy. In the present study, we investigated role of TXNIP on oxidative stress in glomerular mesangial cells (GMCs) cultured in high glucose or normal glucose, and explored the potential mechanism related to TXNIP as well. Methods: Oxidative stress in GMCs under high or normal glucose was detected. TXNIP knockdown by specific siRNA or over expression by pcDNA3.0-TXNIP vector was performed to evaluate the role of TXNIP on injury of GMCs caused by oxidative stress. Activator of AMPK AICAR and AMPK inhibitor Compound C were treated the GMCs. Reactive oxygen species (ROS) and mitochondrial membrane potential were detected by flow cytometry. Activities of superoxide dismutase (SOD) and superoxide dismutase (CAT) were measured by ELISA. Activity of thioredoxin (Trx) was determined using Trx activity assay kit. mRNA expression of AMPK, TXNIP, Trx1 and Trx2 were tested by qRT-PCR. Expressions of P-AMPK, TXNIP and fibronectin proteins were detected by Western blotting. Results: High glucose induced the increase of ROS level, activation of TXNIP, but restricted mitochondrial membrane potential and activities of p-AMPK, SOD and CAT, and Trx. TXNIP siRNA and AICAR inhibited high glucose-induced oxidative stress response in GMCs and fibronectin expression, but promoted cell viability. In contrast, pcDNA3.0-TXNIP and Compound C increased oxidative stress response in normal glucose cultured GMCs, but decreased cell viability. The combined effect of TXNIP siRNA and AICAR on the inhibition of oxidative stress was obviously stronger than that of single use of TXNIP siRNA. Conclusion: TXNIP facilitates the oxidative stress response in GMCs partially through AMPK pathway, which may provide potential therapeutic target for diabetic nephropathy treatment.
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Key words
TXNIP,AMPK,Fibronectin,Oxidative stress,Glomerular mesangial cell
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