Glutaredoxin Desensitizes Lens to Oxidative Stress by Connecting and Integrating Specific Signaling and Transcriptional Regulation for Antioxidant Response

Abstract

Background/Aims: Oxidative stress plays a critical role in the development of cataracts, and glutaredoxins (Grxs) play a major protective role against oxidative stress in the lens. This study aimed to reveal the global regulatory network of Grx1. Methods: Stable isotope labeling by amino acids in cell culture (SILAC) was used in a proteome-wide quantitative approach to identify the Grx1 regulatory signaling cascades at a subcellular resolution in response to oxidative stress. Results: A total of 1,291 proteins were identified to be differentially expressed, which were further categorized into a variety of signaling cascades including redox regulation, apoptosis, cell cycle control, glucose metabolism, protein synthesis, DNA damage response, protein folding, proteasome and others. Thirteen key signaling node molecules representing each pathway were verified. Notably, the subunits of proteasome complexes, which play a pivotal role in preventing cytotoxicity via the degradation of oxidized proteins, were highly enriched by Grx1. By data-dependent network analysis, we found global functional links among these signaling pathways which elucidate how Grx1 integrates the operation of these regulatory networks in an interconnected way for H₂O₂-induced response. Conclusion: Our data provide a system-wide insight into the function of Grx1 and provide a basis for further mechanistic investigation of Grx1 in antioxidant responses in the lens.

Characterization of Heat Shock Protein 60 as an Interacting Partner of Superoxide Dismutase 2 in the Silkworm, Bombyx mori, and Its Response to the Molting Hormone, 20-Hydroxyecdysone

“…Several proteins that interact with mammalian SOD1 and SOD2 have been identified [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. Understanding the peripheral proteins that interact with BmSod1 and BmSod2 can provide important insight into the molecular mechanisms underlying the effects of ROS production on metamorphic events in silkworm.…”

Glutathione S-Transferase T1 Null Genotype is Associated with Susceptibility to Inflammatory Bowel Disease

“…The overproduction of ROS has been found in the inflamed mucosa of IBD patients [16]. Excessive oxidative free radicals can result in cellular stress and facilitate inflammatory reactions, which further result in the development of UC or CD [40-42]. GSTs are enzymes with important roles in the detoxification of electrophilic compounds including ROS [12].…”