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      Protective Effect of Ginsenoside Rg1 on Oxidative Damage Induced by Hydrogen Peroxide in Chicken Splenic Lymphocytes

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          Abstract

          Previous investigation showed that ginsenoside Rg1 (Rg1) extracted from Panax ginseng C.A. Mey has antioxidative effect on oxidative stress in chickens. The present study was designed to investigate the protective effects of Rg1 on chicken lymphocytes against hydrogen peroxide-induced oxidative stress and the potential mechanisms. Cell viability, apoptotic cells, malondialdehyde, activity of superoxide dismutase, mitochondrial membrane potential, and [Ca 2+]i concentration were measured, and transcriptome analysis and quantitative real-time polymerase chain reaction were used to investigate the effect of Rg1 on gene expression of the cells. The results showed that treatment of lymphocytes with H 2O 2 induced oxidative stress and apoptosis. However, pretreatment of the cells with Rg1 dramatically enhanced cell viability, reduced apoptotic cells, and decreased oxidative stress induced by H 2O 2. In addition, Rg1 reduced these H 2O 2-dependent decreases in mitochondrial membrane potential and reversed [Ca 2+]i overload. Transcriptome analysis showed that 323 genes were downregulated and 105 genes were upregulated in Rg1-treated cells. The differentially expressed genes were involved in Toll-like receptors, peroxisome proliferator-activated receptor signaling pathway, and cytokine-cytokine receptor interaction. The present study indicated that Rg1 may act as an antioxidative agent to protect cell damage caused by oxidative stress via regulating expression of genes such as RELT, EDA2R, and TLR4.

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          Redox regulation of fos and jun DNA-binding activity in vitro.

          The proto-oncogenes c-fos and c-jun function cooperatively as inducible transcription factors in signal transduction processes. Their protein products, Fos and Jun, form a heterodimeric complex that interacts with the DNA regulatory element known as the activator protein-1 (AP-1) binding site. Dimerization occurs via interaction between leucine zipper domains and serves to bring into proper juxtaposition a region in each protein that is rich in basic amino acids and that forms a DNA-binding domain. DNA binding of the Fos-Jun heterodimer was modulated by reduction-oxidation (redox) of a single conserved cysteine residue in the DNA-binding domains of the two proteins. Furthermore, a nuclear protein was identified that reduced Fos and Jun and stimulated DNA-binding activity in vitro. These results suggest that transcriptional activity mediated by AP-1 binding factors may be regulated by a redox mechanism.
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            Evolution of the chicken Toll-like receptor gene family: A story of gene gain and gene loss

            Background Toll-like receptors (TLRs) perform a vital role in disease resistance through their recognition of pathogen associated molecular patterns (PAMPs). Recent advances in genomics allow comparison of TLR genes within and between many species. This study takes advantage of the recently sequenced chicken genome to determine the complete chicken TLR repertoire and place it in context of vertebrate genomic evolution. Results The chicken TLR repertoire consists of ten genes. Phylogenetic analyses show that six of these genes have orthologs in mammals and fish, while one is only shared by fish and three appear to be unique to birds. Furthermore the phylogeny shows that TLR1-like genes arose independently in fish, birds and mammals from an ancestral gene also shared by TLR6 and TLR10. All other TLRs were already present prior to the divergence of major vertebrate lineages 550 Mya (million years ago) and have since been lost in certain lineages. Phylogenetic analysis shows the absence of TLRs 8 and 9 in chicken to be the result of gene loss. The notable exception to the tendency of gene loss in TLR evolution is found in chicken TLRs 1 and 2, each of which underwent gene duplication about 147 and 65 Mya, respectively. Conclusion Comparative phylogenetic analysis of vertebrate TLR genes provides insight into their patterns and processes of gene evolution, with examples of both gene gain and gene loss. In addition, these comparisons clarify the nomenclature of TLR genes in vertebrates.
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              Avian toll-like receptors.

              Analysis of the genomes of two distantly related bird species, chicken and zebra finch (divergence of about 100 million years), indicate that there are ten avian toll-like receptors and that five of these, TLR2a, 2b, 3, 4, 5 and 7, are clear orthologs to TLRs found in mammals. Duplication of genes has led to TLR1La and 1Lb, TLR2a and 2b, and two TLR7s in the zebra finch. Avian TLR21 may be orthologous to TLR21 found in fish and amphibians, and avian TLR15, which is phylogenetically related to the TLR2 family, appears to be unique to avian species. While TLR2 is conserved between mammalian and avian species, the other TLR2 family members evolved independently. Dimerization between either of the two avian TLR2 species and TLR1La or 1Lb permits recognition of the same broad range of molecules as recognized by mammalian TLR2 dimerized with either TLR1, 6 and 10. Similarly, while TLR9 has been lost from the avian genome, DNA high in unmethylated CpG motifs is immunostimulatory through avian TLR21 which is absent in mammals. Thus, while some TLR members were commonly retained in both mammals and birds, others were separately lost or gained, or diverged independently; but broadly speaking the TLRs of the two classes of vertebrates evolved to recognize very similar spectra of microbial products. Components of downstream TLR signaling are also mostly conserved but with some losses in avian species; notably, TRAM is absent in avian genomes and, hence, the TRIF/TRAM-dependent signaling pathway utilized by mammals in LPS activation appears to be absent in birds.
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                Author and article information

                Contributors
                Journal
                Oxid Med Cell Longev
                Oxid Med Cell Longev
                OMCL
                Oxidative Medicine and Cellular Longevity
                Hindawi
                1942-0900
                1942-0994
                2019
                18 April 2019
                : 2019
                : 8465030
                Affiliations
                Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China
                Author notes

                Academic Editor: Laura Bravo

                Author information
                http://orcid.org/0000-0002-3847-2906
                http://orcid.org/0000-0002-1287-4552
                http://orcid.org/0000-0002-8266-6791
                Article
                10.1155/2019/8465030
                6501224
                25afe80f-faf9-4cd0-b186-85eda0a3fc04
                Copyright © 2019 Shicheng Bi et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 December 2018
                : 4 March 2019
                Funding
                Funded by: Special Fund for Agro-scientific Research in the Public Interest
                Funded by: National Natural Science Foundation of China
                Award ID: 31172356
                Categories
                Research Article

                Molecular medicine
                Molecular medicine

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