scholarly journals Decline in constitutive proliferative activity in the zebrafish retina with ageing

2021 ◽  
Author(s):  
Ismael Hernandez-Nunez ◽  
Ana Quelle-Regaldie ◽  
Laura Sanchez ◽  
Fatima Adrio ◽  
Eva Candal ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Mitotic Activity ◽  
Proliferative Activity ◽  
Outer Nuclear Layer ◽  
Proliferating Cells ◽  
Adult Retina ◽  
Highly Active ◽  
Cartilaginous Fishes ◽  
Fish Retina ◽  
Mitotic Cells

It is largely assumed that the fish retina shows continuous and active proliferative and neurogenic activity throughout life. This is based on studies in teleost models. However, work in lampreys and cartilaginous fishes has shown that proliferative and mitotic activity is almost absent in adult individuals of these ancient fish groups. Interestingly, when deepening in the teleost literature one finds that claims of a highly active and continuous proliferation in the adult retina are based on studies in which proliferation was not quantified in a comparative way at different life stages or was mainly studied in juveniles/young adults. Here, we performed a systematic and comparative study of the constitutive proliferative activity of the retina from early developing (2 days post-fertilization) to aged (up to 3-4 years post-fertilization) zebrafish. Cell proliferation was analysed by using immunofluorescence against pH3 (marker of mitotic cells) and PCNA (marker of proliferating cells). We observed a decline in cell proliferation in the whole retina with ageing, even despite the occurrence of a wave of secondary proliferation during sexual maturation. Interestingly, during this wave of secondary proliferation the distribution of proliferating and mitotic cells changes from the inner to the outer nuclear layer in the central retina. Importantly, in aged zebrafish there is a virtual disappearance of mitotic activity. Our results showing a decline in proliferative activity of the zebrafish retina with ageing are of crucial importance since it is largely assumed that the fish retina grows continuously throughout life from progenitor cells located in the periphery.

scholarly journals Using Ki-67 Mitotic Activity Markers as a Predictor of the Progression of Adhesions in the Abdominal Cavity

2020 ◽  
Vol 10 (4) ◽  
pp. 412-415
Author(s):  
Irina Shurygina ◽  
Michael Shurygin ◽  
Elena Chepurnykh ◽  
Nataliya Ayushinova
Keyword(s):  
Mitotic Activity ◽  
Proliferative Activity ◽  
Abdominal Cavity ◽  
Control Group ◽  
Proliferative Potential ◽  
Proliferating Cells ◽  
Maximum Increase ◽  
Ki 67 ◽  
Male Wistar Rats ◽  
Experimental Group

Background: Ki-67 is a nuclear protein expressed in all proliferating cells of vertebrates during mitotic cycle phases S, G1, G2, and M, except for G0. Studying this marker is widely used to diagnose the proliferative activity of tumors. However, studying Ki-67 in non-neoplastic diseases attracts much less attention among the researchers. The aim of this study was to assess the possibility of using staining for Ki-67 to identify the proliferative potential of fibroblasts during the formation of adhesions in the abdominal cavity (AC). Methods and Results: Experiments were carried out on male Wistar rats. The adhesion process in AC was simulated in the control group (n=25), and in the experimental group (n=25) with the administration of Seroguard®. Animals were sacrificed on Days 1–30, and the severity of the adhesive process in AC was assessed. Histological sections were prepared and stained for Ki-67. It was found that the animals of the control group had increased severity of the adhesive process in AC during the observation. Maximum increase in severity was registered on Day 30 – 12[9-13] points in the control group and 4[4-4] points in the experimental group (P=0.0079). High proliferative activity of fibroblasts in the control group was detected on Days 3, 7, 14 and 30, which may indicate an active division of fibroblasts and the formation of adhesions in the damaged area. In the experimental group, single Ki-67 positive cells were noted during the entire observation period, which may point to a reduced potential for the formation of adhesions. Conclusion: Our study showed the prospects of using Ki-67 staining to determine the severity of the developing adhesive process in AC, and also revealed one of the possible mechanisms that inhibit the formation of the adhesive process when using Seroguard® – a decrease in the mitotic activity of fibroblasts in the area of peritoneal injury.

scholarly journals Assessment and Imaging of Intracellular Magnesium in SaOS-2 Osteosarcoma Cells and Its Role in Proliferation

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1376
Author(s):  
Concettina Cappadone ◽  
Emil Malucelli ◽  
Maddalena Zini ◽  
Giovanna Farruggia ◽  
Giovanna Picone ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Growth ◽  
Magnesium Deficiency ◽  
Acid Synthesis ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
High Concentration ◽  
Proliferating Cells ◽  
Intracellular Magnesium ◽  
In Cells

Magnesium is an essential nutrient involved in many important processes in living organisms, including protein synthesis, cellular energy production and storage, cell growth and nucleic acid synthesis. In this study, we analysed the effect of magnesium deficiency on the proliferation of SaOS-2 osteosarcoma cells. When quiescent magnesium-starved cells were induced to proliferate by serum addition, the magnesium content was 2–3 times lower in cells maintained in a medium without magnesium compared with cells growing in the presence of the ion. Magnesium depletion inhibited cell cycle progression and caused the inhibition of cell proliferation, which was associated with mTOR hypophosphorylation at Serine 2448. In order to map the intracellular magnesium distribution, an analytical approach using synchrotron-based X-ray techniques was applied. When cell growth was stimulated, magnesium was mainly localized near the plasma membrane in cells maintained in a medium without magnesium. In non-proliferating cells growing in the presence of the ion, high concentration areas inside the cell were observed. These results support the role of magnesium in the control of cell proliferation, suggesting that mTOR may represent an important target for the antiproliferative effect of magnesium. Selective control of magnesium availability could be a useful strategy for inhibiting osteosarcoma cell growth.

scholarly journals Telomerase activation in mouse mammary tumors: lack of detectable telomere shortening and evidence for regulation of telomerase RNA with cell proliferation.

1996 ◽  
Vol 16 (7) ◽  
pp. 3765-3772 ◽  
Author(s):  
D Broccoli ◽  
L A Godley ◽  
L A Donehower ◽  
H E Varmus ◽  
T de Lange
Keyword(s):  
Cell Proliferation ◽  
Tumor Development ◽  
Mammary Tumorigenesis ◽  
Mammary Tumors ◽  
Mammary Glands ◽  
Telomerase Activity ◽  
Telomerase Rna ◽  
Proliferating Cells ◽  
Telomere Shortening ◽  
Mouse Mammary Tumors

Activation of telomerase in human cancers is thought to be necessary to overcome the progressive loss of telomeric DNA that accompanies proliferation of normal somatic cells. According to this model, telomerase provides a growth advantage to cells in which extensive terminal sequence loss threatens viability. To test these ideas, we have examined telomere dynamics and telomerase activation during mammary tumorigenesis in mice carrying a mouse mammary tumor virus long terminal repeat-driven Wnt-1 transgene. We also analyzed Wnt-1-induced mammary tumors in mice lacking p53 function. Normal mammary glands, hyperplastic mammary glands, and mammary carcinomas all had the long telomeres (20 to 50 kb) typical of Mus musculus and did not show telomere shortening during tumor development. Nevertheless, telomerase activity and the RNA component of the enzyme were consistently upregulated in Wnt-1-induced mammary tumors compared with normal and hyperplastic tissues. The upregulation of telomerase activity and RNA also occurred during tumorigenesis in p53-deficient mice. The expression of telomerase RNA correlated strongly with histone H4 mRNA in all normal tissues and tumors, indicating that the RNA component of telomerase is regulated with cell proliferation. Telomerase activity in the tumors was elevated to a greater extent than telomerase RNA, implying that the enzymatic activity of telomerase is regulated at additional levels. Our data suggest that the mechanism of telomerase activation in mouse mammary tumors is not linked to global loss of telomere function but involves multiple regulatory events including upregulation of telomerase RNA in proliferating cells.

scholarly journals MRG15 Regulates Embryonic Development and Cell Proliferation

2005 ◽  
Vol 25 (8) ◽  
pp. 2924-2937 ◽  
Author(s):  
Kaoru Tominaga ◽  
Bhakti Kirtane ◽  
James G. Jackson ◽  
Yuji Ikeno ◽  
Takayoshi Ikeda ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Embryonic Development ◽  
Chromatin Remodeling ◽  
Histone Deacetylases ◽  
Globin Gene ◽  
Immunohistochemical Analysis ◽  
Wild Type ◽  
Proliferating Cells ◽  
Globin Promoter

ABSTRACT MRG15 is a highly conserved protein, and orthologs exist in organisms from yeast to humans. MRG15 associates with at least two nucleoprotein complexes that include histone acetyltransferases and/or histone deacetylases, suggesting it is involved in chromatin remodeling. To study the role of MRG15 in vivo, we generated knockout mice and determined that the phenotype is embryonic lethal, with embryos and the few stillborn pups exhibiting developmental delay. Immunohistochemical analysis indicates that apoptosis in Mrg15 − / − embryos is not increased compared with wild-type littermates. However, the number of proliferating cells is significantly reduced in various tissues of the smaller null embryos compared with control littermates. Cell proliferation defects are also observed in Mrg15 − / − mouse embryonic fibroblasts. The hearts of the Mrg15 − / − embryos exhibit some features of hypertrophic cardiomyopathy. The increase in size of the cardiomyocytes is most likely a response to decreased growth of the cells. Mrg15 − / − embryos appeared pale, and microarray analysis revealed that α-globin gene expression was decreased in null versus wild-type embryos. We determined by chromatin immunoprecipitation that MRG15 was recruited to the α-globin promoter during dimethyl sulfoxide-induced mouse erythroleukemia cell differentiation. These findings demonstrate that MRG15 has an essential role in embryonic development via chromatin remodeling and transcriptional regulation.

Immunohistochemical study of p53 expression in endometrial carcinomas: correlation with markers of proliferating cells and clinicopathologic features

1993 ◽  
Vol 3 (6) ◽  
pp. 363-368 ◽  
Author(s):  
T. Hachisuga ◽  
K. Fukuda ◽  
M. Uchiyama ◽  
N. Matsuo ◽  
T. Iwasaka ◽  
...  
Keyword(s):  
Dna Polymerase ◽  
Proliferative Activity ◽  
P53 Protein ◽  
Myometrial Invasion ◽  
Proliferating Cells ◽  
Ki 67 ◽  
Normal Endometrium ◽  
P53 Expression ◽  
Dna Polymerase Α ◽  
Endometrial Carcinomas

Using anti-p53 (PAb1801 and PAb240), anti-DNA polymerase α and Ki-67 monoclonal antibodies, the expression of p53 was studied in 11 normal endometria, 14 endometrial hyperplasias and 27 endometrial carcinomas and its relationship to the proliferative activity of the tumors was examined. Normal endometria and simple hyperplasias were completely negative for p53. The PAb1801 indices of complex hyperplasias and complex atypical hyperplasias were 2.5±1.8% and 5.0±3.2%, respectively. The PAb1801 indices of grade 1, grade 2 and grade 3 endometrial carcinomas were 10.2±14.2%, 44.4±29/0% and 45.0±32.5%, respectively. These results indicate a progressively enhanced p53 expression in the sequence from normal endometrium, through hyperplasia to carcinoma. A significant correlation between p53 expression and labeling indices of Ki-67 and DNA polymerase α was observed in endometrial carcinomas. The endo-metrial carcinomas with p53 overexpression developed mainly in post-menopausal patients and were frequently high-grade tumors with deep myometrial invasion. These findings may indicate that overexpression of p53 protein contributes to the proliferative activity of the tumor cells.

Contrasting patterns of c-myc and N-myc expression in proliferating, quiescent, and differentiating cells of the embryonic chicken lens

Development ◽  
1992 ◽  
Vol 115 (3) ◽  
pp. 813-820
Author(s):  
L.L. Harris ◽  
J.C. Talian ◽  
P.S. Zelenka
Keyword(s):  
Cell Proliferation ◽  
Protein Product ◽  
Mrna Levels ◽  
Lens Fiber ◽  
Proliferating Cells ◽  
Fiber Cells ◽  
Embryonic Chicken ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation

The present study uses the polymerase chain reaction and in situ hybridization to examine c-myc and N-myc mRNA in the embryonic chicken lens at 6, 10, 14 and 19 days of development and compares the pattern of expression obtained with the developmental pattern of cell proliferation and differentiation. In the central epithelium, c-myc mRNA levels were proportional to the percentage of proliferating cells throughout development. N-myc mRNA expression in this region was relatively low and showed no correlation with cell proliferation. The ratio of N-myc to c-myc mRNA increased markedly with the onset of epithelial cell elongation and terminal fiber cell differentiation, although both c-myc and N-myc mRNAs continued to be expressed in postmitotic, elongating cells of the equatorial epithelium and in terminally differentiating lens fiber cells. Thus, increased expression of N-myc, a gene whose protein product may compete with c-myc protein for dimerization partners, accompanies the dissociation of c-myc expression and cell proliferation during terminal differentiation of lens fiber cells.

scholarly journals Cyclophosphamide has Long-Term Effects on Proliferation in Olfactory Epithelia

2019 ◽  
Vol 45 (2) ◽  
pp. 97-109
Author(s):  
Nora Awadallah ◽  
Kara Proctor ◽  
Kyle B Joseph ◽  
Eugene R Delay ◽  
Rona J Delay
Keyword(s):  
Cell Proliferation ◽  
Vomeronasal Organ ◽  
Cell Renewal ◽  
Loss Of Function ◽  
Long Term Effects ◽  
Proliferating Cells ◽  
Taste System ◽  
Main Olfactory Epithelium ◽  
Sensory Layer ◽  
Chemotherapy Patients

Abstract Chemotherapy patients often experience chemosensory changes during and after drug therapy. The chemotherapy drug, cyclophosphamide (CYP), has known cytotoxic effects on sensory and proliferating cells of the taste system. Like the taste system, cells in the olfactory epithelia undergo continuous renewal. Therefore, we asked if a single injection of 75 mg/kg CYP would affect cell proliferation in the anterior dorsomedial region of the main olfactory epithelium (MOE) and the vomeronasal organ (VNO) from 0 to 125 days after injection. Both epithelia showed a decrease in Ki67-labeled cells compared to controls at day 1 and no Ki67+ cells at day 2 postinjection. In the sensory layer of the MOE, cell proliferation began to recover 4 days after CYP injection and by 6 days, the rate of proliferation was significantly greater than controls. Ki67+ cells peaked 30 days postinjection, then declined to control levels at day 45. Similar temporal sequences of initial CYP-induced suppression of cell proliferation followed by elevated rates peaking 30–45 days postinjection were seen in the sustentacular layer of the MOE and all 3 areas (sensory, sustentacular, marginal) of the VNO. CYP affected proliferation in the sensory layer of the MOE more than the sustentacular layer and all 3 areas of the VNO. These findings suggest that chemotherapy involving CYP is capable of affecting cell renewal of the olfactory system and likely contributes to clinical loss of function during and after chemotherapy.

scholarly journals Cell proliferation controls body size growth, tentacle morphogenesis, and regeneration in hydrozoan jellyfish Cladonema pacificum

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7579 ◽  
Author(s):  
Sosuke Fujita ◽  
Erina Kuranaga ◽  
Yu-ichiro Nakajima
Keyword(s):  
Cell Proliferation ◽  
Body Size ◽  
Environmental Changes ◽  
Size Control ◽  
Cellular Mechanisms ◽  
Proliferating Cells ◽  
Size Growth ◽  
Local Cell ◽  
Proliferating Cell

Jellyfish have existed on the earth for around 600 million years and have evolved in response to environmental changes. Hydrozoan jellyfish, members of phylum Cnidaria, exist in multiple life stages, including planula larvae, vegetatively-propagating polyps, and sexually-reproducing medusae. Although free-swimming medusae display complex morphology and exhibit increase in body size and regenerative ability, their underlying cellular mechanisms are poorly understood. Here, we investigate the roles of cell proliferation in body-size growth, appendage morphogenesis, and regeneration using Cladonema pacificum as a hydrozoan jellyfish model. By examining the distribution of S phase cells and mitotic cells, we revealed spatially distinct proliferating cell populations in medusae, uniform cell proliferation in the umbrella, and clustered cell proliferation in tentacles. Blocking cell proliferation by hydroxyurea caused inhibition of body size growth and defects in tentacle branching, nematocyte differentiation, and regeneration. Local cell proliferation in tentacle bulbs is observed in medusae of two other hydrozoan species, Cytaeis uchidae and Rathkea octopunctata, indicating that it may be a conserved feature among hydrozoan jellyfish. Altogether, our results suggest that hydrozoan medusae possess actively proliferating cells and provide experimental evidence regarding the role of cell proliferation in body-size control, tentacle morphogenesis, and regeneration.

scholarly journals Translocation of protein tyrosine phosphatase Pez/PTPD2/PTP36 to the nucleus is associated with induction of cell proliferation

2000 ◽  
Vol 113 (17) ◽  
pp. 3117-3123 ◽  
Author(s):  
C. Wadham ◽  
J.R. Gamble ◽  
M.A. Vadas ◽  
Y. Khew-Goodall
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Nuclear Protein ◽  
Vascular Endothelial Cells ◽  
Tyrosine Phosphatase ◽  
Subcellular Localisation ◽  
Vascular Endothelial ◽  
Proliferating Cells ◽  
Wound Edge

Pez is a non-transmembrane tyrosine phosphatase with homology to the FERM (4.1, ezrin, radixin, moesin) family of proteins. The subcellular localisation of Pez in endothelial cells was found to be regulated by cell density and serum concentration. In confluent monolayers Pez was cytoplasmic, but in cells cultured at low density Pez was nuclear, suggesting that it is a nuclear protein in proliferating cells. This notion is supported by the loss of nuclear Pez when cells are serum-starved to induce quiescence, and the rapid return of Pez to the nucleus upon refeeding with serum to induce proliferation. Vascular endothelial cells normally exist as a quiescent confluent monolayer but become proliferative during angiogenesis or upon vascular injury. Using a ‘wound’ assay to mimic these events in vitro, Pez was found to be nuclear in the cells that had migrated and were proliferative at the ‘wound’ edge. TGFbeta, which inhibits cell proliferation but not migration, inhibited the translocation of Pez to the nucleus in the cells at the ‘wound’ edge, further strengthening the argument that Pez plays a role in the nucleus during cell proliferation. Together, the data presented indicate that Pez is a nuclear tyrosine phosphatase that may play a role in cell proliferation.

scholarly journals Wnt Activity and Cell Proliferation Are Coupled to Extracellular Vesicle Release in Multiple Organoid Models

2021 ◽  
Vol 9 ◽  
Author(s):  
Gyöngyvér Orsolya Sándor ◽  
András Áron Soós ◽  
Péter Lörincz ◽  
Lívia Rojkó ◽  
Tünde Harkó ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Disease Diagnosis ◽  
Extracellular Vesicle ◽  
Cellular Heterogeneity ◽  
Ductal Adenocarcinoma ◽  
Diagnostic Tools ◽  
Proliferating Cells ◽  
Pathway Activation ◽  
A Cell ◽  
Potential Tool

Extracellular vesicles (EV) are considered as a potential tool for early disease diagnosis; however, factors modifying EV release remain partially unknown. By using patient-derived organoids that capture the cellular heterogeneity of epithelial tissues, here we studied the connection between the Wnt-producing microniche and EV secretion in multiple tissues. Although nearly all cells in pancreatic ductal (PD) and pancreatic ductal adenocarcinoma (PDAC) samples expressed porcupine (PORCN), an enzyme critical for Wnt secretion, only a subpopulation of lung bronchiolar (NL) and lung adenocarcinoma (LUAD) organoid cells produced active Wnt. The microniche for proliferating cells was shaped not only by PORCN + cells in NL and LUAD organoids but also by fibroblast-derived EVs. This effect could be blocked by using Wnt secretion inhibitors. Whereas inhibiting Wnt secretion in PD NL or LUAD organoids critically changed both cell proliferation and EV release, these were uncoupled from each other in PDAC. Sorting for CD133 identified a cell population in the LUAD microniche that produced organoids with a high percentage of PORCN + and proliferating cells and an elevated EV secretion, which may explain that CD133 marks LUAD cells with malignant behavior. Collectively, we show here that high cell proliferation rate, induced by Wnt pathway activation, is coupled to a higher EV release, a critical finding that may be considered when developing EV-based diagnostic tools.

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