Thioredoxin (Trx): A redox target and modulator of cellular senescence and aging-related diseases

Yang, Bowen; Lin, Yumeng; Huang, Yibo; Shen, Ying-Qiang; Chen, Qianming

doi:10.1016/j.redox.2024.103032

Cited by 7 publications

(1 citation statement)

References 505 publications

(575 reference statements)

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“…Cheng et al also indicated that thioredoxin is essential for motility and contributes to host infection of Listeria monocytogenes via redox interactions [ 13 ]. The function of trxB remains a topic of exploration [ 35 , 36 ]. As a crucial component of the thioredoxin system, trxB plays a pivotal role in oxidative stress, virulence modulation, growth regulation, drug resistance, and other essential processes [ 37 , 38 , 39 ].…”

Section: Discussionmentioning

confidence: 99%

Critical Involvement of the Thioredoxin Reductase Gene (trxB) in Salmonella Gallinarum-Induced Systemic Infection in Chickens

Zhu,

Hu,

Ojima

et al. 2024

Microorganisms

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Salmonella enterica serovar Gallinarum biovar Gallinarum (SG) causes fowl typhoid, a notifiable infectious disease in poultry. However, the pathogenic mechanism of SG-induced systemic infection in chickens remains unclear. Thioredoxin reductase (TrxB) is a redox protein crucial for regulating various enzyme activities in Salmonella serovar, but the role in SG-induced chicken systemic infection has yet to be determined. Here, we constructed a mutant SG strain lacking the trxB gene (trxB::Cm) and used chicken embryo inoculation and chicken oral infection to investigate the role of trxB gene in the pathogenicity of SG. Our results showed that trxB::Cm exhibited no apparent differences in colony morphology and growth conditions but exhibited reduced tolerance to H2O2 and increased resistance to bile acids. In the chicken embryo inoculation model, there was no significant difference in the pathogenicity of trxB::Cm and wild-type (WT) strains. In the chicken oral infection, the WT-infected group exhibited typical clinical symptoms of fowl typhoid, with complete mortality between days 6 and 9 post infection. In contrast, the trxB::Cm group showed a 100% survival rate, with no apparent clinical symptoms or pathological changes observed. The viable bacterial counts in the liver and spleen of the trxB::Cm-infected group were significantly reduced, accompanied by decreased expression of cytokines and chemokines (IL-1β, IL-6, IL-12, CXCLi1, TNF-α, and IFN-γ), which were significantly lower than those in the WT group. These results show that the pathogenicity of the trxB-deficient strain was significantly attenuated, indicating that the trxB gene is a crucial virulence factor in SG-induced systemic infection in chickens, suggesting that trxB may become a potentially effective target for controlling and preventing SG infection in chickens.

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Section: Discussionmentioning

confidence: 99%

Critical Involvement of the Thioredoxin Reductase Gene (trxB) in Salmonella Gallinarum-Induced Systemic Infection in Chickens

Zhu,

Hu,

Ojima

et al. 2024

Microorganisms

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An antireductant approach ameliorates misfolded proinsulin-induced hyperglycemia and glucose intolerance in male Akita mice

Mattocks,

Ommi,

Malloy

et al. 2024

GeroScience

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Protein folding in the endoplasmic reticulum (ER) requires a high ratio of oxidized to reduced glutathione (GSSG/rGSH). Since the GSSG/rGSH depends on total glutathione (tGSH = GSSG + rGSH) levels, we hypothesized that limiting GSH biosynthesis will ameliorate protein misfolding by enhancing the ER oxidative milieu. As a proof-of-concept, we used DL-buthionine-(S,R)-sulfoximine (BSO) to inhibit GSH biosynthesis in Akita mice, which are prone to proinsulin misfolding. We conducted a 2-week intervention to investigate if BSO was safe and a 6-week intervention to find its effect on glucose intolerance. In both cohorts, male heterozygous Akita (AK) and wild-type (WT) mice were continuously administered 15 mM BSO. No adverse effects were observed on body weight, food intake, and water intake in either cohort. Unaltered levels of plasma aspartate and alanine aminotransferases, and cystatin-C, indicate that BSO was safe. BSO-induced decreases in tGSH were tissue-dependent with maximal effects in the kidneys, where it altered the expression of genes associated with GSH biosynthesis, redox status, and proteostasis. BSO treatment decreased random blood glucose levels to 80% and 67% of levels in untreated mice in short-term and long-term cohorts, respectively, and 6-h fasting blood glucose to 82% and 74% of levels in untreated mice, respectively. BSO also improved glucose tolerance by 37% in AK mice in the long-term cohort, without affecting insulin tolerance. Neither glucose tolerance nor insulin tolerance were affected in WT. Data indicate that BSO might treat misfolded proinsulin-induced glucose intolerance. Future studies should investigate the effect of BSO on proinsulin misfolding and if it improves glucose intolerance in individuals with Mutant Insulin Diabetes of Youth. Graphical abstract 1) Male heterozygous C57BL/6-Ins2Akita/J (AK) mice suffer from misfolded proinsulin-induced glucose intolerance. (a) Proinsulin misfolding occurs due to a genetic mutation in Ins2 gene that substitutes Cys with Tyr, (b) Due to heterozygosity, AK mice produce both wild-type and mutated proinsulin, (c) Mutated proinsulin forms aggregates with itself and with the bystander native proinsulin, (d) Proinsulin aggregation results in lower functional insulin, and (e) AK mice suffer from impaired glucose tolerance. 2) Treating mice with BSO improved glucose tolerance. (a) Mice were treated with continuous administration of 15 mM DL -buthionine-(S,R)-sulfoximine (BSO), an inhibitor of glutathione biosynthesis (b), BSO treatment increased the renal mRNA quantity of several genes involved in glutathione biosynthesis, glutathione redox status, and proteostasis, (c) we hypothesize that BSO-induced changes in cellular redox status and gene expression ameliorates proinsulin aggregation and increases the functional insulin levels in β-cells, and (d) BSO treatment significantly improved glucose intolerance in AK mice. Note: AUC - Area under the curve, GCL -γ-g-glutamylcysteine ligase, GS - Gluatthione synthetase.

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Design, synthesis and biological evaluation of novel curcumin-fluorouracil hybrids as potential anti-cancer agents

Wang,

Li,

Zhang

et al. 2024

Biochemical Pharmacology

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Thioredoxin (Trx): A redox target and modulator of cellular senescence and aging-related diseases

Cited by 7 publications

References 505 publications

Critical Involvement of the Thioredoxin Reductase Gene (trxB) in Salmonella Gallinarum-Induced Systemic Infection in Chickens

Critical Involvement of the Thioredoxin Reductase Gene (trxB) in Salmonella Gallinarum-Induced Systemic Infection in Chickens

An antireductant approach ameliorates misfolded proinsulin-induced hyperglycemia and glucose intolerance in male Akita mice

Design, synthesis and biological evaluation of novel curcumin-fluorouracil hybrids as potential anti-cancer agents

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