Evaluation of Glutathione Peroxidase 4 role in Preeclampsia

Peng, Xinguo; Lin, Yan; Li, Jinling; Liu, Mengchun; Wang, Jingli; Li, Xueying; Liu, Jingjing; Jia, Xiaoyan; Jing, Zhongcui; Huang, Zuzhou; Chu, Kaiqiu; Liu, Shiguo

doi:10.1038/srep33300

Cited by 28 publications

(25 citation statements)

References 37 publications

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“… GPx1 Pro198Leu SNP affects risk of Kashin-Beck disease [ 17 ]. GPX4 rs713041 SNP affects risk of pre-eclampsia [ 18 ]. GPX4 reduces lipid peroxides accumulated during ferroptosis into non-toxic lipid alcohols [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Selenium and selenoproteins in viral infection with potential relevance to COVID-19

et al. 2020

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Selenium is a trace element essential to human health largely because of its incorporation into selenoproteins that have a wide range of protective functions. Selenium has an ongoing history of reducing the incidence and severity of various viral infections; for example, a German study found selenium status to be significantly higher in serum samples from surviving than non-surviving COVID-19 patients. Furthermore, a significant, positive, linear association was found between the cure rate of Chinese patients with COVID-19 and regional selenium status. Moreover, the cure rate continued to rise beyond the selenium intake required to optimise selenoproteins, suggesting that selenoproteins are probably not the whole story. Nonetheless, the significantly reduced expression of a number of selenoproteins, including those involved in controlling ER stress, along with increased expression of IL-6 in SARS-CoV-2 infected cells in culture suggests a potential link between reduced selenoprotein expression and COVID-19-associated inflammation. In this comprehensive review, we describe the history of selenium in viral infections and then go on to assess the potential benefits of adequate and even supra-nutritional selenium status. We discuss the indispensable function of the selenoproteins in coordinating a successful immune response and follow by reviewing cytokine excess, a key mediator of morbidity and mortality in COVID-19, and its relationship to selenium status. We comment on the fact that the synthetic redox-active selenium compound, ebselen, has been found experimentally to be a strong inhibitor of the main SARS-CoV-2 protease that enables viral maturation within the host. That finding suggests that redox-active selenium species formed at high selenium intake might hypothetically inhibit SARS-CoV-2 proteases. We consider the tactics that SARS-CoV-2 could employ to evade an adequate host response by interfering with the human selenoprotein system. Recognition of the myriad mechanisms by which selenium might potentially benefit COVID-19 patients provides a rationale for randomised, controlled trials of selenium supplementation in SARS-CoV-2 infection.

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Section: Introductionmentioning

confidence: 99%

Selenium and selenoproteins in viral infection with potential relevance to COVID-19

et al. 2020

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“…We found significant difference for the genotype of IL-22 rs2227485 and GPX4 rs713041 associated with the mild, severe, and early-onset PE. Furthermore, the GPX4 rs713041 C allele has the higher risk for pathogenesis of PE [27,29]. Those that are just single genes without systematic haplotype analysis.…”

Section: Discussionmentioning

confidence: 99%

“…Genotyping of 8 and 10 candidate SNPs related to inflammatory and oxidative stress, respectively, (Tables 1 and 2) was performed using predesigned TaqMan allelic discrimination real-time PCR followed by partial validation by Sanger sequencing. All women who were genotyped were retrospectively confirmed from our previous studies [23][24][25][26][27][28][29][30][31][32][33][34].…”

Section: Methodsmentioning

confidence: 99%

Haplotype Analysis of Candidate Genes Involved in Inflammation and Oxidative Stress and the Susceptibility to Preeclampsia

Chen

Zhao

Wang

et al. 2020

Journal of Immunology Research

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Unbalanced inflammatory reactions and oxidative stress are inseparably interconnected, and both may play crucial roles in the pathophysiological mechanisms of preeclampsia (PE). In the published previous studies, we have genotyped for SNPs that related to inflammation (rs2227485, rs153109, rs17855750, rs2027432, rs2275913, rs763780, rs4819554, and rs13015714) and oxidative stress (rs1695, rs4680, rs1800566, rs4807542, rs713041, rs7579, rs230813, rs1004467, rs3824755, and rs9932581) to investigate whether these polymorphisms were associated with susceptibility to PE in a Chinese Han population. In this present study, we collected these data of experimental and clinical from above studies for haplotype analysis of inflammation-related SNPs in 631 PE patients and 720 normal pregnancy and oxidative stress-related SNPs in 342 PE patients and 457 normal pregnancies for susceptibility to PE. The data of genotype distribution and allele frequency comparisons after correction for multiple comparisons (P/8 or P/10) showed 2 among the 8 candidate inflammation-related SNPs have significant differences (rs2027432 genotype χ2=407.377,p<0.001,p<0.00625). Moreover, the minor alleles of rs2027432 T (minor allele χ2=450.923,p<0.001,p<0.00625;OR=21.439,95%CI=15.181‐30.278) and rs4819554 G (minor allele χ2=163.465,p<0.001,p<0.00625;OR=5.814,95%CI=4.380‐7.719) were confirmed as risk allele of PE, respectively. Our analysis revealed rs2027432 (TT) of NLRP3 and rs4819554 (GG) of IL-17RA are risk factors for PE. However, no significant difference was found at the oxidative stress-related SNPs. In the candidate loci for oxidative stress, we also identified 3 SNP matches (rs4807542 and rs713041, rs230813 and rs75799, rs1004467 and rs3824755) that had high linkage disequilibrium (LD) with each other and were selected as a block (r2=0.98,r2=0.97,r2=0.97,r2>0.9), and the GT and GC haplotypes of rs4807542 and rs713041 in GPX4 showed significant differences between the PE and control groups (χ2=5.143,p=0.0233,p<0.05;χ2=6.373,p=0.0116,p<0.05). So, we inferred that polymorphisms of NLRP3 rs2027432 and IL-17RA rs4819554, which are related to inflammation, and the rs713041 variant of GPX4, which is related to oxidative stress, were associated with susceptibility to PE. The GT and GC haplotypes of rs4807542 and rs713041 in GPX4 may increase the risk of PE in the Chinese Han population.

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“…This decrease was associated with pre-pregnancy obesity in women [ 27 ]. GPx4 also plays important role in preeclampsia in women, because decreased expression of this enzyme may lead to preeclampsia development [ 28 ]. On the other hand, the total lack of information about GPx4 involvement during the preimplantation period of pregnancy was the main stimulus for this research work.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Glutathione Peroxidase 4 in Rat Oocytes, Preimplantation Embryos, and Selected Maternal Tissues during Early Development and Implantation

Kreheľová

Kovaříková

Domoráková

et al. 2021

IJMS

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This study aimed to describe glutathione peroxidase 4 (GPx4) in rat oocytes, preimplantation embryos, and female genital organs. After copulation, Sprague Dawley female rats were euthanized with anesthetic on the first (D1), third (D3), and fifth days of pregnancy (D5). Ovaries, oviducts, and uterine horns were removed, and oocytes and preimplantation embryos were obtained. Immunohistochemical, immunofluorescent, and Western blot methods were employed. Using immunofluorescence, we detected GPx4 in both the oocytes and preimplantation embryos. Whereas in the oocytes, GPx4 was homogeneously diffused, in the blastomeres, granules were formed, and in the blastocysts, even clusters were present mainly around the cell nuclei. Employing immunohistochemistry, we detected GPx4 inside the ovary in the corpus luteum, stroma, follicles, and blood vessels. In the oviduct, the enzyme was present in the epithelium, stroma, blood vessels, and smooth muscles. In the uterus, GPx4 was found in the endometrium, myometrium, blood vessels, and stroma. Moreover, we observed GPx4 positive granules in the uterine gland epithelium on D1 and D3 and cytoplasm of fibroblasts forming in the decidua on D5. Western blot showed the highest GPx4 levels in the uterus and the lowest levels in the ovary. Our results show that the GPx4 is necessary as early as in the preimplantation development of a new individual because we detected it in an unfertilized oocyte in a blastocyst and not only after implantation, as was previously thought.

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Evaluation of Glutathione Peroxidase 4 role in Preeclampsia

Cited by 28 publications

References 37 publications

Selenium and selenoproteins in viral infection with potential relevance to COVID-19

Selenium and selenoproteins in viral infection with potential relevance to COVID-19

Haplotype Analysis of Candidate Genes Involved in Inflammation and Oxidative Stress and the Susceptibility to Preeclampsia

Characterization of Glutathione Peroxidase 4 in Rat Oocytes, Preimplantation Embryos, and Selected Maternal Tissues during Early Development and Implantation

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