Nuclear factor E2-related factor-2 (Nrf2) expression and regulation in male reproductive tract

Wajda, Anna; Łapczuk, Joanna; Grabowska, Marta; Słojewski, Marcin; Urasińska, Elżbieta; Droździk, Marek

doi:10.1016/j.pharep.2015.07.005

Cited by 41 publications

(20 citation statements)

References 26 publications

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“…These differences in Nrf2/Keap1 expression suggested that in epididymis, there was the most alteration in gene expressions involved in the Nrf2 signaling pathway and testicular heating occurred during cryptorchidism that had various effects on different parts of reproductive system. Wajda et al, previously explained that Nrf2 expression is higher in rat's corpus of epididymis than its liver, testis, and other parts of epididymis (8). Epididymis plays important roles in sperm maturation, motility, and storage (21).…”

Section: Discussionmentioning

confidence: 99%

“…The components involved in the expression of Nrf2 signaling pathway vary between tissue and species. This detoxification mechanism plays a protective role in the reproductive system (8). It was observed that Nrf2 knockdown in male mice causes spermatogenesis disruption (9) and decreases the expression of Nrf2 reported in males with low sperm motility (10).…”

Section: Introductionmentioning

confidence: 99%

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Role of Epididymis and Testis in Nuclear Factor Erythroid 2-Related Factor 2 Signaling in Mouse Experimental Cryptorchidism

Asl

Mashayekhi

Bayat

et al. 2019

Iran Red Crescent Med J

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Background: Cryptorchidism is a common gonadal disease in neonates that promotes oxidative stress and reactive oxygen spices production following the presence of testicles in ectopic places. Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling could prevent oxidative stress damage through the Nrf2-driven antioxidants. Objectives: The current study aimed at evaluating the pattern of gene expressions related to this pathway in testis and epididymis of mice experimentally subjected to cryptorchidism. Methods: The current experimental study was conducted on 48 male mice randomly divided into six groups at

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Role of Epididymis and Testis in Nuclear Factor Erythroid 2-Related Factor 2 Signaling in Mouse Experimental Cryptorchidism

Asl

Mashayekhi

Bayat

et al. 2019

Iran Red Crescent Med J

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“…Nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2), an essential protein in cellular antioxidant defence, is also expressed in germ cells, Leydig cells and Sertoli cells. Generally, Nrf2 is usually located in the cytoplasm, where it is tagged and degraded via ubiquitination by Kelch‐like ECH‐associated protein 1 (Keap1) (Wajda et al, ). After Nrf2 is activated and translocated into the nucleus, it binds to the antioxidant response element (ARE), to further mediate the expression of many downstream intracellular antioxidants and phase II detoxification enzymes, including NAD(P)H:quinone oxidoreductase1 (NQO1), haem oxygenase‐1 (HO‐1) and glutamate–cysteine ligase catalytic subunit (GCLC) (Loboda, Damulewicz, Pyza, Jozkowicz, & Dulak, ).…”

Section: Introductionmentioning

confidence: 99%

Protective effect of Dioscorea zingiberensis ethanol extract on the disruption of blood–testes barrier in high‐fat diet/streptozotocin‐induced diabetic mice by upregulating ZO‐1 and Nrf2

Zhou

Zhang

et al. 2020

Andrologia

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Testicular injury is the primary pathogenesis of diabetes‐induced male infertility. Dioscorea zingiberensis (DZ), a traditional Chinese medicine (TCM) including saponins, flavonoids and cellulose, is used to treat diseases in the reproductive system. But the protective effects of DZ on diabetes‐induced testicular injury remain poorly understood. In this study, the therapeutic effects of chronic oral DZ treatment on testis impairment in a diabetic mouse model were explored by assessing sperm morphology, blood–testes barrier (BTB) integrity and testicular histological examination. Our results showed that DZ significantly reversed BTB disruption, testicular tissue injury and abnormal sperm morphology in diabetic mice. Interestingly, diabetes‐induced disruption of the BTB was associated with a decrease in the tight junction (TJ) protein zonula occludens‐1 (ZO‐1). Dioscorea zingiberensis effectively increased ZO‐1 expression in testis tissue to restore the integrity of the BTB. Moreover, DZ treatment significantly reduced hyperglycaemia‐induced increases in malondialdehyde (MDA) and 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG) levels. Further mechanistic studies revealed that DZ substantially enhanced the expression of Nrf2, NOQ1 and HO‐1, which indicated that DZ exerts potential antioxidant effects against testicular tissue damage via the activation of Nrf2. In conclusion, the protective effects of DZ rely on repairing the integrity of the BTB and on reducing oxidative stress damage by mediating ZO‐1 and Nrf2. The study contributes to discovering the DZ possible mechanism of action.

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“…28 It is regulated byNrf2. 35,36 Expression of Nqo1 is induced by oxidative stress. 37 Nqo1 is involved in cellular antioxidant defense and plays a pivotal role in the detoxification of quinine.…”

Section: Discussionmentioning

confidence: 99%

<p>Network Pharmacology Combined with Transcriptional Analysis to Unveil the Biological Basis of Astaxanthin in Reducing the Oxidative Stress Induced by Diabetes Mellitus</p>

Sun

Tahir

et al. 2020

DMSO

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Purpose Astaxanthin (Ast) has been reported to reduce oxidative stress induced by diabetes mellitus (DM). The aim of this research was to give a systematic overview of the biological basis for this process. Methods Ast-targeted proteins were collected from the BATMAN database, Comparative Toxicogenomics Database, and STITCH database. Putative DM-related protein targets were collected from the GeneCards database. A DM-rat model was then built with streptozotocin (STZ) combined with a high-sugar, high-fat diet for 30 days. Total cholesterol (TC), triglycerides (TGs), and insulin levels were examined using whole tail-vein blood from overnight-fasted rats. SOD, GSH, and MDA activy was detected in liver tissue ( p <0.05). In addition, we used RNA-sequencing analysis to detect gene-transcription level in liver tissue of rats and GO biological process analysis to show all the log 2 FC≥2 genes in the Ast-fed DM rats compared with the DM group using the STRING database. Ast-intersecting targets were collected with Venn analysis. Docking analysis between Ast and targeted proteins was down with the SwissDock server. Ast targets–pathway networks were built using Cytoscape 3.7.2 software. Results A total of 120 Ast-targeted proteins and 13,784 DM-related targets were collected. Ast functioned in reducing TC, TG, and MDA levels, promoting SOD activity and GSH expression, and alleviating islet-cell injury in Ast-fed DM rats compared with DM control rats. Furthermore, genes involved in MAPK, TNF, AMPK, and FOXO signaling pathways were differently expressed in Ast-treated DM rats compared with DM rats. The differentially expressed genes were enriched in euchromatin, thyroid cancer, and metaphase-plate congression. Three Ast-intersecting targets — Col5A1, Nqo1, and Notch2 — were then identified. We found possible binding patterns of Ast with Nqo1 and Notch2, respectively. Ast targets–pathway networks were finally built to show a systematic overview of how Ast works in multiple pathways to reduce oxidative stress. Taken together, Ast is predicted to target Col5A1, Nqo1, and Notch2 to form a network of systemic pharmacological effects to: 1) promote insulin-releasing balance and relieve insulin resistance, 2) reduce testicular cell apoptosis, and 3) maintain normal size in marginal-zone B cells and inhibit autoimmune DM, all of which contribute to the balance of lipid metabolism and reduction of oxidative stress in DM patients. Conclusion Ast functions in reducing oxidative stress in DM rats by regulating a variety of targets to form a comprehensive antioxidative network.

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Nuclear factor E2-related factor-2 (Nrf2) expression and regulation in male reproductive tract

Cited by 41 publications

References 26 publications

Role of Epididymis and Testis in Nuclear Factor Erythroid 2-Related Factor 2 Signaling in Mouse Experimental Cryptorchidism

Role of Epididymis and Testis in Nuclear Factor Erythroid 2-Related Factor 2 Signaling in Mouse Experimental Cryptorchidism

Protective effect of Dioscorea zingiberensis ethanol extract on the disruption of blood–testes barrier in high‐fat diet/streptozotocin‐induced diabetic mice by upregulating ZO‐1 and Nrf2

<p>Network Pharmacology Combined with Transcriptional Analysis to Unveil the Biological Basis of Astaxanthin in Reducing the Oxidative Stress Induced by Diabetes Mellitus</p>

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