Changes in the heart of neonatal rats after cryptosporidial gastroenteritis of different degrees of severity

Anatskaya, Olga V.; Matveev, I. V.; Сидоренко, Н. В.; Kharchenko, M. V.; Кропотов, А. В.; Vinogradov, Alexander E.

doi:10.1134/s0022093013050071

Cited by 8 publications

(14 citation statements)

References 19 publications

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“…For instance, a positive correlation was established between hyperpoliploidy of cardiomyocytes and expression of fetal phenotype determined based on the induction of embryonic markers: beta myosin heavy chain, factor HIF1 α (hypoxia factor 1 α), an increase in the number and size of the nucleoli, as well as increased proliferation potential (Anatskaya, Vino gradov, 2002, 2004a, 2004b2013a, 2013b. In addi tion, there is also indirect evidence of manifestation of embryonic features during cardiomyocyte polyp loidization.…”

Section: Resultsmentioning

confidence: 99%

Pairwise comparison of mammalian transcriptomes associated with the effect of polyploidy on the expression activity of developmental gene modules

Anatskaya

Ērenpreisa²,

Nikolsky

et al. 2016

Cell Tiss. Biol.

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Design and development of highly sensitive methods of bioinformatics are associated with the need to obtain information on the impact of epigenetic changes on gene activity. One factor causing such changes is polyploidy. Polyploidy maintains the balance of gene dosage and, therefore, can have only a slight effect on their expression. Currently, there is no unified concept with respect to the impact of polyploidy on transcriptomes. To clarify this issue, we developed an integrative bioinformatics method aimed at accessing weak effects of polyploidy on the activity of genes by implementing a pairwise cross transcriptome analysis of mammalian tissues with varying degrees of ploidy. The advantage of this method is its ability to distinguish between variable species and tissue specific effects and evolutionarily conserved ones. The applicability of the developed methodology was demonstrated by analysis of genetic modules and protein interaction net works involved in the coordination of developmental processes. We carried out analysis of full transcriptome data for human and mouse heart and liver. We discovered that genes activated by ploidy are enriched (i.e., are presented above the random level) in transcriptomes of biological processes of the Gene Ontology (GO) data base and in pathways in the KEGG database related to organism development, morphogenesis, and stem cell biology (including the signaling pathways Hippo, Pi3K, WNT, Hedgehog, and TGF β) to a greater extent than genes suppressed by ploidy. The structure and composition of the protein interaction networks con structed for ploidy regulated genes confirmed the results of analysis of gene modules. Thus, our data are the first to demonstrate that polyploidy can regulate the modules of organism development by increasing their activity.

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Section: Resultsmentioning

confidence: 99%

Pairwise comparison of mammalian transcriptomes associated with the effect of polyploidy on the expression activity of developmental gene modules

Anatskaya

Ērenpreisa²,

Nikolsky

et al. 2016

Cell Tiss. Biol.

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“…The goal of the study was to investigate the postponed effects of neonatal Cryptosporidium gastroenteritis on C3HA mice innate immunity and growth. The interest to this problem was fuelled by the studies indicating that neonatal cryptosporidiosis may trigger hyperpolyploid cardiomyopathy, hepatopathy, and malignancy in rodents [32][33][34][35] and by the data confirming that the immune system impairment plays a key role in the development of these diseases. [36][37][38] Currently, the nature of the relationships between cryptosporidiosis and the immune system state of the infected animal remains poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Natural killer cell activity irreversibly decreases after Cryptosporidium gastroenteritis in neonatal mice

Filatova

Knyazev

Skarlato

et al. 2018

Parasite Immunology

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Cryptosporidiosis causes persistent diarrhoea in infants, immunocompromised patients and elderly persons. Long-term consequences of the disease include increased risk of malignancy, cardiomyopathy and gastrointestinal inflammation. This study aimed to investigate prolonged effects of cryptosporidiosis on innate immunity and growth in neonatal C3HA mice. The disease was challenged by Cryptosporidium parvum oocyst inoculation into 7-day-old animals. The mice whose intestine smears contained 3-5 or 6 and more oocysts per microscopic field at the day 5 after infection were considered as mildly or severely infected, correspondingly. To determine natural killer cell (NK) activity, we applied H-uridine cytotoxic assay to the animals at 5-68 days after infection using K562 cells as targets. At severe infection, there was a statistically significant 1.5-2.0 fold decline of body mass, spleen mass and spleen cellularity that persisted in animals of all ages. Accordingly, NK cytotoxicity showed even more drastic drop reaching 2.7-3.0 folds that was statistically significant in all animals. At mild infection, the discovered effects were less pronounced and reached significance only in some age groups. Thus, our study provides evidence that NK cells show long-term cytotoxic activity decrease following Cryptosporidium infection in neonatal mice, particularly in severe disease.

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“…In human and warm-blooded animals, polyploidy can be a part of normal postnatal morphogenetic programs and can be a manifestation of response to pathological stimuli and diseases. Thus, polyploid cells arise in normal organogenesis of heart, neuronal glia, cerebellum, neocortex, retina, liver, placenta, blood vessels, skin, blood, and other organs [ 3 , 22 , 71 , 72 , 73 , 74 ] and in atherosclerosis, neurodegenerative disorders, cardiovascular diseases, wound healing, inflammation, diabetes, cancer, and other pathologies [ 1 , 7 , 8 , 72 , 74 , 75 , 76 , 77 , 78 , 79 , 80 ]. Despite the prevalence in normal physiology and pathology, the functional significance of polyploidy still is not clear.…”

Section: Somatic Polyploidymentioning

confidence: 99%

Polyploidy as a Fundamental Phenomenon in Evolution, Development, Adaptation and Diseases

Anatskaya

Vinogradov

2022

IJMS

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DNA replication during cell proliferation is ‘vertical’ copying, which reproduces an initial amount of genetic information. Polyploidy, which results from whole-genome duplication, is a fundamental complement to vertical copying. Both organismal and cell polyploidy can emerge via premature cell cycle exit or via cell-cell fusion, the latter giving rise to polyploid hybrid organisms and epigenetic hybrids of somatic cells. Polyploidy-related increase in biological plasticity, adaptation, and stress resistance manifests in evolution, development, regeneration, aging, oncogenesis, and cardiovascular diseases. Despite the prevalence in nature and importance for medicine, agri- and aquaculture, biological processes and epigenetic mechanisms underlying these fundamental features largely remain unknown. The evolutionarily conserved features of polyploidy include activation of transcription, response to stress, DNA damage and hypoxia, and induction of programs of morphogenesis, unicellularity, and longevity, suggesting that these common features confer adaptive plasticity, viability, and stress resistance to polyploid cells and organisms. By increasing cell viability, polyploidization can provide survival under stressful conditions where diploid cells cannot survive. However, in somatic cells it occurs at the expense of specific function, thus promoting developmental programming of adult cardiovascular diseases and increasing the risk of cancer. Notably, genes arising via evolutionary polyploidization are heavily involved in cancer and other diseases. Ploidy-related changes of gene expression presumably originate from chromatin modifications and the derepression of bivalent genes. The provided evidence elucidates the role of polyploidy in evolution, development, aging, and carcinogenesis, and may contribute to the development of new strategies for promoting regeneration and preventing cardiovascular diseases and cancer.

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Changes in the heart of neonatal rats after cryptosporidial gastroenteritis of different degrees of severity

Cited by 8 publications

References 19 publications

Pairwise comparison of mammalian transcriptomes associated with the effect of polyploidy on the expression activity of developmental gene modules

Pairwise comparison of mammalian transcriptomes associated with the effect of polyploidy on the expression activity of developmental gene modules

Natural killer cell activity irreversibly decreases after Cryptosporidium gastroenteritis in neonatal mice

Polyploidy as a Fundamental Phenomenon in Evolution, Development, Adaptation and Diseases

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