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01 May 2016 : Laboratory Research  

Thioredoxin-Interacting Protein (TXNIP) Suppresses Expression of Glutamine Synthetase by Inducing Oxidative Stress in Retinal Muller Glia Under Diabetic Conditions

Jia ZhouAB, Xi ShenACEG, Qiong LuDF, Min ZhangDF

DOI: 10.12659/MSM.895916

Med Sci Monit 2016; 22:1460-1466

Abstract

BACKGROUND: Diabetic retinopathy (DR) is a progressive neurodegenerative disease with early-stage symptoms such as dysfunction of Muller cells, which leads to ganglion cell death. Its pathogenesis is probably associated with oxidative stress and a recently discovered protein, thioredoxin-interacting protein (TXNIP). 

MATERIAL AND METHODS: To explore the role of TXNIP in DR, we cultured Muller cells under diabetic conditions, and then used immunohistochemistry, Western blot, and RT-PCR to detect the expression level of TXNIP under diabetic conditions. We demonstrated the expression level of glutamine synthetase (GS) when TXNIP was inhibited. To explore the potential pathway of TXNIP-induced cell damage in DR, we confirmed the role of IL-1β under diabetic conditions. 

RESULTS: Diabetes induces TXNIP expressions at mRNA levels, but shows the opposite effect on GS. IL-1β plays an important role in this pathway. Azaserine effectively increased the expression of GS via attenuating the expression of TXNIP. 

CONCLUSIONS: This study demonstrates the role of TXNIP and its mechanism in DR, provides a possible treatment for DR, and lays a new theoretical foundation for the clinical treatment of DR and other diabetic microvascular changes. 

Keywords: Azaserine - metabolism, Animals, Carrier Proteins - metabolism, Cells, Cultured, Diabetes Mellitus, Experimental - pathology, Ependymoglial Cells - pathology, Fluorescent Antibody Technique, Gene Expression Regulation, Glucose - toxicity, Glutamate-Ammonia Ligase - metabolism, Interleukin-1beta - metabolism, Mice, RNA, Messenger - metabolism, Retina - pathology, Thioredoxins - metabolism

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750