Cation transport by bone marrow cells from vitamin-E-deficient mice

1989 ◽  
Vol 76 (2) ◽  
pp. 78-80 ◽  
Author(s):  
K. I. Altman ◽  
H. M�hlensiepen ◽  
O. Muzik ◽  
L. E. Feinendegen
Keyword(s):  
Bone Marrow ◽  
Vitamin E ◽  
Bone Marrow Cells ◽  
Cation Transport ◽  
Deficient Mice ◽  
Marrow Cells

Therapeutic angiogenesis in diabetic apolipoprotein E-deficient mice using bone marrow cells, functional hemangioblasts and metabolic intervention

2010 ◽  
Vol 209 (2) ◽  
pp. 403-414 ◽  
Author(s):  
Maria Luisa Balestrieri ◽  
Shi-Jiang Lu ◽  
Filomena de Nigris ◽  
Alfonso Giovane ◽  
Sharon Williams-Ignarro ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Apolipoprotein E ◽  
Bone Marrow Cells ◽  
Therapeutic Angiogenesis ◽  
Deficient Mice ◽  
Marrow Cells

scholarly journals 442. Decreased Survival and Engraftment in Adult ADA-Deficient Mice Co-Transplanted With Uncorrected Lineage-Positive Bone Marrow Cells Combined With Gene-Corrected Lineage-Negative Bone Marrow Cells

2015 ◽  
Vol 23 ◽  
pp. S175
Author(s):  
Denise A. Carbonaro-Sarracino ◽  
Michael L. Kaufman ◽  
Xiangyang Jin ◽  
Sabine Geiger ◽  
Danielle Clark ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Deficient Mice ◽  
Marrow Cells

Hematopoietic Cells from Gadd45a, Gadd45b Deficent Mice Exhibit Altered Myelopoiesis and Higher Apoptosis after Cytokine Treatment.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1697-1697
Author(s):  
Shiv K. Gupta ◽  
Mamta Gupta ◽  
Barbara Hoffman ◽  
Dan A. Liebermann
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Myeloid Cells ◽  
Methyl Cellulose ◽  
Myeloid Cell ◽  
Cell Maturation ◽  
Wild Type ◽  
Wild Type Littermate ◽  
Deficient Mice ◽  
Marrow Cells

Abstract Growth arrest and DNA damage, Gadd45 gene family members are rapidly induced by genotoxic agents as well as by apoptosis and differentiation inducing cytokines. Their role in hemetopoiesis, wherein proliferation, differentiation and apoptosis integrate to maintain cellular homeostasis, is not clear. Using bone marrow cells from gadd45a or gadd45b deficient and wild type littermate mice we have investigated the role of Gadd45 proteins in cytokine induced myeloid cell differentiation in vitro. Bone marrow cells obtained from either gadd45a or gadd45b deficient mice displayed compromised cytokines (IL3, GM-CSF, M-CSF or G-CSF) induced myelopoiesis, resulting in a quantitatively decreased population of mature myeloid cells. Immuno-phenotyping with antibodies to cell surface molecules associated with myeloid cell maturation confirmed impaired myeloid cell maturation in Gadd45a or b deficient bone marrow cells treated with the above cytokines. Analysis of apoptosis by annexin-V and PI staining followed by FACS analysis showed a substantially higher apoptosis in Gadd45a−/− as well as gadd45b−/− cells compared to wild type cells after treatment with M-CSF or G-CSF. Gadd45a−/− as well as gadd45b−/− bone marrow cells were found to be less clonogenic in methylcellulose medium. Morphologically compact and round colonies consisting of immature myeloid cells prevailed over dispersed- colonies consisting of mature myeloid cells in gadd45- deficient cells cultured in methyl cellulose containing IL-3. Furthermore, colony re-plating assay showed better self-renewal abilities in gadd45a−/− as well as gadd45b−/− progenitors, compared to wild type progenitor cells. Altered myelopoiesis in gadd45 a or b deficient mice was further confirmed in vivo by intra-peritoneal administration of sodium casienate - a known inducer of inflammatory response and myelopoiesis in mice bone marrow. Sodium casienate failed to enhance myelopoiesis in gadd45a or gadd45b deficient mice bone marrow, while wild type littermate mice showed a rapid induction of myelopoiesis. Simultaneously peritoneal exudates collected from gadd45 deficient mice consisted of 2–3 fold less myeloid cells compared to age matched wild type control mice after sodium casienate treatment. Gadd45a−/− or gadd45b−/− mice showed a slow recovery after myelo-suppressive effect of antimetabolite 5-Fluorouracil, which further confirmed that gadd45 deficiency leads to delayed myelopoiesis in mouse. Mechanistic aspects of Gadd45 deficiency, which results in impaired myelopoiesis are under investigation.

Myeloid Progenitor Cells from Gadd45a and Gadd45b-Deficient Mice Are Sensitized to Genotoxic-Stress Induced Apoptosis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4239-4239
Author(s):  
Mamta Gupta ◽  
Shiv K. Gupta ◽  
Arthur G. Balliet ◽  
Barbara Hoffman ◽  
Dan A. Lieberman
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Bone Marrow Cells ◽  
Genotoxic Stress ◽  
Wild Type ◽  
Myeloid Progenitor ◽  
Myeloid Progenitor Cells ◽  
Induced Apoptosis ◽  
Deficient Mice ◽  
Marrow Cells

Abstract GADD45 (Growth arrest and DNA damge) regulates cell growth following exposure to diverse stimuli. It has been shown that, mice lacking the gadd45a gene exhibit genomic instability and increased carcinogenesis, but the exact role of the gadd45 family genes still remains unclear. In this study we have aimed at determining the effect of gadd45a or gadd45b deficiency on the response of bone marrow derived myeloid cells to genotoxic stress agents by using gadd45a or gadd45b null mice. We have found that myeloid progenitor cells from gadd45a or gadd45b-null mice are more sensitive to ultraviolet-radiation (UV), VP-16 or daunorubicin induced apoptosis. Introduction of wild-type gadd45 into gadd45-deficient bone marrow cells restored the wild-type apoptotic phenotype. In-vitro colony formation following stress responses has shown that bone marrow cells from gadd45a or gadd45b-deficient mice have a decreased ability to form haematopoetic colonies. Gadd45a or gadd45b-deficient bone marrow cells also displayed defective G2/M cell cycle checkpoint following exposure to either UV and V-16 but were still able to undergo G2/M arrest following exposure to daunorubicin, indicating the existence of different G2/M checkpoints in response to these anticancer agents. Taken together these findings identify gadd45a or gadd45b as anti-apoptotic gene(s), and suggests that the absence of gadd45a or gadd45b results in higher susceptibility of haematopoetic cells to UV radiation and certain anticancer drugs.

Samd9L-Deficient Mice Develop Myeloid Malignancies Mimicking Human Diseases with Monosomy 7

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 869-869
Author(s):  
Hirotaka Matsui ◽  
Akiko Nagamachi ◽  
Yuko Ozaki ◽  
Hiroya Asou ◽  
Hiroaki Honda ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myeloid Leukemia ◽  
Bone Marrow Cells ◽  
Human Diseases ◽  
Newborn Mice ◽  
Monosomy 7 ◽  
Myeloid Malignancies ◽  
Myeloid Neoplasms ◽  
Deficient Mice ◽  
Marrow Cells

Abstract Abstract 869 Monosomy 7 is a common chromosomal abnormality found frequently in MDS and AML. We previously identified a common microdeletion cluster in subband 7q21.3 in JMML patients (Asou et al., 2009). This cluster contains three poorly characterized genes: sterile alpha motif (SAM) domain-9 (Samd9) which is absent in mice, Samd9-like (Samd9L) and Miki (LOC253012). In this study we established and characterized Samd9L-deficient mice in detail and found that these mice develop myeloid malignancies that mimic human diseases with −7/7q-. Samd9L −/− (n=10), Samd9L+/− (n=11) and Samd9L+/+ (n=13) littermates were observed for signs of illness for 2 years. All but one Samd9L+/+ mice maintained consistent WBC counts and hemoglobin levels throughout the observation period. Meanwhile, seven among 21 Samd9L+/− and Samd9L−/− mice developed neutropenia and/or anemia and 2 mice showed an apparent WBC increase after the age of 18 months. Based on Bethesda proposals for classification, the types and frequencies of myeloid diseases demonstrated by mice included myeloid dysplasia (5/10 Samd9L−/−; 2/11 Samd9L+/−), myeloid leukemia (1/10 Samd9L−/−; 1/11 Samd9L+/−) and myeloproliferative disease (1/11 Samd9L+/−). To determine whether loss of the Samd9L gene predisposes mice to myeloid diseases, newborn mice were injected with MOL4070A retrovirus which selectively induces AML or MDS in mice with propensity to myeloid malignancies. There was a significant effect, in that almost all Samd9L+/− (12/14) and Samd9L−/− (10/12) mice died from myeloid neoplasms, roughly one year earlier than mice that developed spontaneous myeloid malignancies without retroviral infection. In contrast, only 2 of 30 MOL4070A-infected Samd9L+/+ mice developed myeloid diseases. Unlike uninfected Samd9L+/− and Samd9L−/− mice, which preferentially developed MDS (7/21), 16 of 26 virus-infected mice showed myeloid leukemias of various subtypes including undifferentiated, myelomonocytic, or monocytic leukemia that expressed combinations of surface markers for the granulocytic, monocytic, erythroid or megakaryocytic lineage. By applying inverse PCR method, two common retrovirus integration sites, Evi1 and Fbxl10 genes, were identified in leukemic samples specifically from Samd9L−/− and Samd9L+/− mice. The enhanced incidence of leukemia in mice with Samd9L-deficiency by Evi1 or Fbxl10 overexpression was further analyzed by transplanting Samd9L−/− or Samd9L+/+ bone marrow cells transduced with retrovirus expressing Evi1 or Fbxl10. All mice (11/11) receiving transferred Samd9L−/−Evi1 bone marrow cells died from hematopoietic malignancies, particularly myeloid disorders (10/11). While not a statistically significant result, we also found that three of 13 mice receiving transferred Samd9L −/−Fbxl10 bone marrow cells developed myeloid malignancies. The development of MDS in Samd9L+/− and Samd9L−/− mice of advancing age mimics the typical clinical association between −7/7q- and sporadic MDS in elderly humans, while development of wide-variety of myeloid leukemia subtypes in retrovirus-infected Samd9L+/− and Samd9L−/− mice indicates that Samd9L gene-deficiency can promote diverse leukemogenic pathways, mimicking another clinical feature of −7/7q-: i.e., deep involvement in therapy-related AML/MDS as well as AML/MDS among patients with a propensity for myeloid diseases. As we reported last year, Samd9L protein localizes to the early endosome. Cells expressing Samd9L at low levels internalize ligand-bound cytokine receptors normally, but there is a delay in homotypic fusion of endosomes that results in prolonged cellular activation to cytokine signals. Moreover, colony replating assay revealed that Samd9L+/− and Samd9L−/− bone marrow cells maintain colony forming ability beyond 7th plating. Although detailed mechanisms remain to be elucidated, we hypothesize that excess cytokine-receptor signaling due to Samd9/Samd9L insufficiency induces self-renewal of hematopoietic stem cells and/or delays in differentiation of early progenitors, resulting in the development of myeloid neoplasms in cooperation with genetic and age-related epigenetic alterations. Disclosures: No relevant conflicts of interest to declare.

The Roles of Stat3 and ERK in G-CSF Signaling.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2172-2172
Author(s):  
Kenjirou Kamezaki ◽  
Kazuya Shimoda ◽  
Akihiko Numata ◽  
Masumi Yoshie ◽  
Masahiro Yamamoto ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Bone Marrow Cells ◽  
Hematopoietic Cells ◽  
Negative Regulator ◽  
Neutrophil Granulocyte ◽  
Proliferation And Differentiation ◽  
Socs3 Expression ◽  
Deficient Mice ◽  
Marrow Cells

Abstract G-CSF specifically stimulates the proliferation and differentiation of cells that are committed to the neutrophil-granulocyte lineage. We examined the role of stat3 in G-CSF signaling using the Cre-loxP recombination system. Although Stat3 was thought to be essential for the transduction of G-CSF-induced cell proliferation and differentiation signals, mice deficient for Stat3 in hematopoietic cells show neutrocytosis and infiltration of cells into the digestive tract. The number of progenitor cells in the neutrophil lineage is not changed, and G-CSF-induced proliferation of progenitor cells and prolonged neutrophil survival were observed in Stat3-deficient mice. In hematopoietic cells from Stat3-deficient mice, trace levels of SOCS3, a negative regulator of granulopoiesis, were observed, and SOCS3 expression was not induced by G-CSF stimulation. Stat3 null bone marrow cells displayed a significant activation of ERK1/2 under basal conditions, and the activation of ERK was enhanced and sustained by G-CSF stimulation. Furthermore, the augmented proliferation of Stat3-deficient bone marrow cells in response to G-CSF was dramatically decreased by addition of a MEK1 inhibitor. These results indicate that Stat3 functions as a negative regulator of G-CSF signaling by inducing SOCS3 expression, and ERK activation is the major factor responsible for inducing the proliferation of hematopoietic cells in response to G-CSF.

Gadd45a and Gadd45b Protect Haematopoetic Cells from Ultraviolet Radiation Induced Apoptosis Via Distinct Signaling Pathways.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1258-1258
Author(s):  
Mamta Gupta ◽  
Shiv K. Gupta ◽  
Barbara Hoffman ◽  
Dan A. Liebermann
Keyword(s):  
Bone Marrow ◽  
Ultraviolet Radiation ◽  
Cell Survival ◽  
Signaling Pathways ◽  
Bone Marrow Cells ◽  
Myeloid Cells ◽  
Genotoxic Stress ◽  
Induced Apoptosis ◽  
Deficient Mice ◽  
Marrow Cells

Abstract Gadd45 expression, which is stress inducible, has been associated with growth arrest, but the exact role of gadd45 family genes in apoptosis still remains unclear. We have found that myeloid progenitor cells from gadd45a and gadd45b-deficient mice are more sensitive to ultra-violet radiation, VP-16 or daunorubicin induced apoptosis. indicating that gadd45a or gadd45b protect haematopoetic cells from DNA damaging agents. To determine, how gadd45a or gadd45b proteins exert their anti-apoptotic function, bone marrow cells from wild-type and gadd45a or gadd45b deficient mice were exposed to ultraviolet radiation (UV) and analyzed for expression of stress responsive kinases, including JNK and p38. It was observed that P38 and JNK were activated in wt bone marrow cells in response to UV but not in bone marrow cells defecient in gadd45a. Also, the transcription factor NF-kB was activated in wt bone marrow cells, but not in gadd45a−/− cells. The pharmacological inhibitor SB203580 specific for p38, increased apoptosis in reponse to UV, indicating that p38 is implicated in signaling myeloid cell survival. SB203580 was observed also to inhibit the expression of certain NF-kB target genes, including cIAP-1, c-IAP-2, bcl-2 and bcl-xl, in gadd45a+/+ cells but not in gadd45a deficient bone marrow cells. Taken together this data provides first evidence for the role gadd45a plays in the control of hematopoietic cell survival in response to UV, via modulation of P38 MAPK and NF-kB signaling pathways. Unlike in gadd45a−/− bone marrow cells, p38 activation appeared not to be impaired in gadd45b−/− cells, indicating that gadd45b is not involved in p38 activation in myeloid cells. However, UV induced JNK activation was sustained in gadd45b−/− myeloid cells compared to wt cells, indicating that gadd45b is a negative modulator of UV induced JNK signaling in myeloid cells. UV induced activation of MKK4 an upstream regulator of JNK also was impaired in gadd45b−/−. NF-kB was also found activated in wt cells, but not in gadd45b−/− cells. This data indicates that in bone marrow cells exposed to UV, NF-kB induced expression of Gadd45b plays a protective role against UV induced apoptosis via inhibition of MKK4 kinase which in turn results in suppression of JNK activity. Taken together this data provides evidence that Gadd45a and Gadd45b protect haematopoetic cells from genotoxic-stress induced apoptosis via distinct signaling pathways.

An Electron Microscopic Study of Blood and Bone Marrow in Vitamin E-Deficient Pigs

1968 ◽  
Vol 5 (6) ◽  
pp. 520-537 ◽  
Author(s):  
Inger Nafstad ◽  
Per H. J. Nafstad
Keyword(s):  
Bone Marrow ◽  
Vitamin E ◽  
Microscopic Study ◽  
Electron Microscopic Study ◽  
Bone Marrow Cells ◽  
Myeloid Cells ◽  
Erythroid Cells ◽  
Electron Microscopic ◽  
Microscopic Appearance ◽  
Marrow Cells

The ultrastructure of blood and bone marrow cells in vitamin E-deficient pigs was studied and correlated with the light microscopic appearance. Earlier light microscopic observations indicating an inadequate erythroid production were confirmed and supplemented. Furthermore, evidence of increased destruction of erythroid cells and abnormalities in formation of myeloid cells were observed.

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