scholarly journals Reform of Hematopoietic, Apoptotic and Oxidative Disturbance Induced by Accumulated γ-Irradiation in Rat’s Bone Marrow via Curative Efficacy of Bradykinin Potentiating Factor Isolated from Bee Venom

2021 ◽  
Vol 0 (0) ◽  
pp. 0-0
Author(s):  
Hesham F. Hasan ◽  
Shereen M. Galal
Keyword(s):  
Bone Marrow ◽  
Bee Venom ◽  
Γ Irradiation

Impact of 2 Gy γ-irradiation on the hallmark characteristics of human bone marrow-derived MSCs

2021 ◽  
Author(s):  
Masaki Iwasa ◽  
Sumie Fujii ◽  
Aya Fujishiro ◽  
Taira Maekawa ◽  
Akira Andoh ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Γ Irradiation

Slug Plays an Essential Role in the Radioprotection of Hematopoietic Progenitors In Vivo by Antagonizing p53-Mediated Apoptotic Pathways.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 31-31
Author(s):  
Wen-Shu Wu ◽  
Dong Xu ◽  
Stefan Heinrichs ◽  
A. Thomas Look
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Leukemia Cells ◽  
Dependent Manner ◽  
Wild Type ◽  
Γ Irradiation ◽  
Aberrant Expression ◽  
Hematopoietic Stem ◽  
Myeloid Progenitors

Abstract An antiapoptotic role for Slug/Snail in mammals was suggested by studies in C. elegans, where CES-1/Scratch, a member of the Slug/Snail superfamily, was found to control the apoptotic death of NSM sister neurons by acting as a transcriptional repressor of EGL-1, a BH3-only proapoptotic protein. Identification of Slug as the target gene of the E2A-HLF oncoprotein in human pro-B leukemia cells led us to demonstrate its antiapoptotic function in IL-3-dependent murine pro-B cells. In contrast to its aberrant expression in pro-B leukemia cells, endogenous Slug is normally expressed in both LT-HSC and ST-HSC, as well as committed progenitors of the myeloid series, but not in pro-B and pro-T cells, implying its function in myelopoiesis. Using Slug−/− mice produced in our laboratory, we showed that these knockouts are much more radiosensitive than Slug+/− and wild-type mice, and that apoptotic cells increase significantly in the hematopoietic progenitor cells of Slug−/− mice as compared to wild-type mice following γ-irradiation, indicating a radioprotective function in vivo. We showed here that although the development of myeloid progenitors is not impaired under steady-state conditions, their repopulation is incomplete γ-irradiated in in Slug−/− mice. We demonstrate further the radiation-induced death of Slug−/− mice is exclusively a result of bone marrow failure with no apparent contribution from systemic injures to other tissues. By two-way bone marrow transplantation, we provide firm evidence that Slug protects mice from γ-irradiation-induced death in a cell-autonomous manner. Interestingly, regenerative capacity of hematopoietic stem cells (HSC) was retained in irradiated Slug−/− mice, which could be rescued by wild-type bone marrow cells after irradiation, indicating that Slug exerts its radioprotective function in myeloid progenitors rather than HSCs. Furthermore, we establish that Slug radioprotects mice by antagonizing downstream of the p53-mediated apoptotic signaling through inhibition of the p53-resposive proapoptotic gene Puma, leading in turn to inhibition of the mitochondria-dependent apoptotic pathway activated by γ-irradiation in myeloid progenitors. More interestingly, we observed that Slug is inducible by γ-irradiation in a p53-dependent manner. Together, our findings implicate a novel Slug-mediated feedback mechanism by which p53 control programmed cell death in myeloid progenitor cells in vivo in response to γ-irradiation.

Thrombopoietin-Mimetic Romiplostim Confers the Complete Survival Rate to Mice Exposed to Lethal Ionizing Radiation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2390-2390 ◽  
Author(s):  
Masaru Yamaguchi ◽  
Tokuhisa Hirouchi ◽  
Mitsuru Chiba ◽  
Satoru Monzen ◽  
Hironori Yoshino ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Blood Cells ◽  
Bone Marrow Cells ◽  
Hematopoietic Progenitor Cells ◽  
Peripheral Blood Cells ◽  
Blood Cell Count ◽  
Hematopoietic Progenitor ◽  
Γ Irradiation ◽  
Radiation Induced ◽  
Marrow Cells

Abstract Radiation-related casualties following exposure to a lethal dose of ionizing radiation show severe acute radiation syndromes (ARS) involving bone marrow death and gastrointestinal death. ARS cause decreases in red blood cell count, white blood cell count, platelet count and gastrointestinal dysfunction, finally leading to death caused by systemic bleeding. Therefore, reconstitution and restoration of hematopoiesis is a top priority. Although bone marrow transplantation (BMT) is also available for recovery from radiation-induced bone marrow damage, BMT for victims in radiation accidents has many limitations, including histocompatibility, age constraints, HLA type and the fact that immunosuppression would be required to reduce the risk of graft versus host rejection. In contrast, pharmacological approaches can accommodate a large number of victims with few limitations. Our previous study showed that the combined administration of erythropoietin, granulocytecolony stimulating factor and nandrolone decanoate after lethal ionizing irradiation resulted in the survival of approximately 50% of irradiated mice at day 30. When a c-Mpl agonist (Romiplostim: RP) was added to this protocol, 100% survival was obtained. Finally, we found that RP play a key role in the survival of irradiated mice. In the present study, we examined the effects of RP alone on mice exposed to lethal radiation. RP was administered at a dosage of 50 μg/kg of body weight/day to 8-weekold female C57BL/6JJcl mice for 1, 3, or 5 days immediately following exposure to a lethal 7 Gy dose of 137Cs γ-rays. The condition of each animal was analyzed via morphological evaluations of the small intestine and various parameters such as the numbers of peripheral blood cells, bone marrow cells, and hematopoietic progenitor cells along with cell surface antigen expression. By day 30, all untreated irradiated control mice died, whereas RP administration for 3 or 5 consecutive days after irradiation led to a 100% survival rate among the irradiated mice. At this time, the numbers of peripheral blood cells, bone marrow cells and hematopoietic progenitor cells were not significantly different between RP-untreated non-irradiated and RP-treated irradiated mice. In addition, the expression of macrophages, granulocytes and erythroid progenitors-related cell surface antigens on the bone marrow cells was significantly recovered in RP-treated irradiated mice compared to RP-untreated irradiated mice until day 20 after γ-irradiation. And, to estimate the effects of RP on gastrointestinal tissues in each individual, morphological evaluation H&E stain of the small intestine was performed until day 20 after γ-irradiation. As a result, RP promoted the recovery of gastrointestinal tissues damages in RP-treated irradiated mice compared to RP-untreated irradiated mice. Regarding cell death, radiation-induced gamma-H2AX expression in the nuclear of bone marrow cell was significantly decreased in RP-treated irradiated mice compared to RP-untreated irradiated mice immediately and after a period of 24 hours following a lethal 7 Gy dose of X-irradiation, indicating that the rate of apoptotic bone marrow cells was significantly decreased by RP-treatment. Meanwhile, 53BP1, which is well known as non-homologous end joining (NHEJ) factor, was significantly increased, showing that RP promoted NHEJ DNA repair in bone marrow cells treated with RP. These results demonstrate that c-Mpl agonist RP promotes the recovery of serious damages caused by lethal irradiation to the hematopoietic and gastrointestinal systems, and RP might be a useful radiomitigator in the case of ARS. Disclosures No relevant conflicts of interest to declare.

Chromosome aberrations induced in human bone-marrow cells by therapeutical local γ irradiation

1972 ◽  
Vol 16 (1) ◽  
pp. 103-109 ◽  
Author(s):  
E.K. Pyatkin ◽  
N.N. Alexsandrov ◽  
A.I. Vorobyev ◽  
S.A. Petrova ◽  
I.I. Suskov
Keyword(s):  
Bone Marrow ◽  
Chromosome Aberrations ◽  
Bone Marrow Cells ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Γ Irradiation ◽  
Marrow Cells

scholarly journals Radiation Impacts Early Atherosclerosis by Suppressing Intimal LDL Accumulation

2021 ◽  
Author(s):  
Jiro Ikeda ◽  
Corey A Scipione ◽  
Sharon Hyduk ◽  
Marwan G Althagafi ◽  
Jawairia Atif ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Single Cell ◽  
Neutral Lipid ◽  
Aortic Arch ◽  
Myeloid Cell ◽  
Transcript Abundance ◽  
Γ Irradiation ◽  
Transport Pathways ◽  
Total Body ◽  
Aortic Intima

Rationale: Bone marrow transplantation (BMT) is used frequently to study the role of hematopoietic cells in atherosclerosis, but aortic arch lesions are smaller in mice after BMT. Objective: To identify the earliest stage of atherosclerosis inhibited by BMT and elucidate potential mechanisms. Methods and Results: Ldlr -/- mice underwent total body γ-irradiation, bone marrow reconstitution and 6-week recovery. Atherosclerosis was studied in the ascending aortic arch and compared to mice without BMT. In BMT mice neutral lipid and myeloid cell topography were lower in lesions after feeding a cholesterol-rich diet (CRD) for 3, 6 and 12 weeks. Lesion coalescence and height were suppressed dramatically in mice post-BMT, whereas lateral growth was inhibited minimally. Targeted radiation to the upper thorax alone reproduced the BMT phenotype. Classical monocyte recruitment, intimal myeloid cell proliferation and apoptosis did not account for the post-BMT phenotype. Neutral lipid accumulation was reduced in 5-day lesions, thus we developed quantitative assays for LDL accumulation and paracellular leakage using DiI-labeled human LDL and rhodamine B-labeled 70kD dextran. LDL accumulation was dramatically higher in the intima of Ldlr -/- relative to Ldlr +/+ mice, and was inhibited by injection of HDL mimics, suggesting a regulated process. LDL, but not dextran, accumulation was lower in mice post-BMT both at baseline and in 5-day lesions. Since the transcript abundance of molecules implicated in LDL transcytosis was not significantly different in the post-BMT intima, transcriptomics from whole aortic arch intima, and at single cell resolution, was performed to give insights into pathways modulated by BMT. Conclusions: Radiation exposure inhibits LDL entry into the aortic intima at baseline and the earliest stages of atherosclerosis. Single cell transcriptomic analysis suggests that LDL uptake by endothelial cells is diverted to lysosomal degradation and reverse cholesterol transport pathways. This reduces intimal accumulation of lipid and impacts lesion initiation and growth.

scholarly journals Parp-2 is required to maintain hematopoiesis following sublethal γ-irradiation in mice

Blood ◽  
2013 ◽  
Vol 122 (1) ◽  
pp. 44-54 ◽  
Author(s):  
Jordi Farrés ◽  
Juan Martín-Caballero ◽  
Carlos Martínez ◽  
Juan J. Lozano ◽  
Laura Llacuna ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dna Damage Response ◽  
Irradiation Dose ◽  
Essential Role ◽  
Bone Marrow Failure ◽  
Γ Irradiation ◽  
Genetic Inactivation ◽  
Key Points ◽  
Damage Response ◽  
Parp 1

Key Points Genetic inactivation of Parp-2 in mice, but not of Parp-1, resulted in bone marrow failure in response to sublethal γ-irradiation dose. Parp-2 plays an essential role in the DNA damage response in HSPC maintaining hematopoietic homeostasis under stress conditions.

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