scholarly journals PBX1 Attenuates Hair Follicle-Derived Mesenchymal Stem Cell Senescence and Apoptosis by Alleviating Reactive Oxygen Species-Mediated DNA Damage Instead of Enhancing DNA Damage Repair

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuan Wang ◽  
Yutong Sui ◽  
Aobo Lian ◽  
Xing Han ◽  
Feilin Liu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Stem Cells ◽  
Dna Damage ◽  
Dna Repair ◽  
Stem Cell ◽  
Hair Follicle ◽  
Cellular Senescence ◽  
Cell Senescence ◽  
Oxygen Species ◽  
Age Related

Tissues and organs undergo structural deterioration and functional decline during aging. DNA damage is considered a major cause of stem cell senescence. Although stem cells develop sophisticated DNA repair systems, when the intrinsic and extrinsic insults exceed the DNA repair capacity, cellular senescence, and age-related diseases inevitably occur. Therefore, the prevention and alleviation of DNA damage is an alternative to DNA repair in attenuating stem cell senescence and preventing age-related diseases. Pre-B-cell leukaemia homeobox 1 (PBX1) participates in maintaining the pluripotency of human embryonic and haematopoietic stem cells. Our recent studies showed that PBX1 promotes hair follicle-derived mesenchymal stem cell (HF-MSC) proliferation, decreases cellular senescence and apoptosis, and enhances induced pluripotent stem cell generation. Whether PBX1 attenuates HF-MSC senescence and apoptosis by alleviating DNA damage or by enhancing DNA repair remains unknown. In this study, we aimed to determine the effects of PBX1 on the intrinsic ROS or extrinsic H2O2-induced cellular senescence of HF-MSCs. To this end, we generated HF-MSCs overexpressing either PBX1, or poly (ADP-ribose) polymerase 1, or both. Our results showed that PBX1 overexpression attenuates HF-MSC senescence and apoptosis by alleviating reactive oxygen species (ROS)-mediated DNA damage instead of enhancing DNA repair. This is the first study to report that PBX1 attenuates stem cell senescence and apoptosis by alleviating DNA damage. It provides new insight into the mechanism of stem cell senescence and lays the foundation for the development of strategies for age-related disease prevention and treatment, and in particular, hair follicle repair and regeneration.

scholarly journals A reactive oxygen species-generating, cyclooxygenase-2 inhibiting, cancer stem cell-potent tetranuclear copper(ii) cluster

2017 ◽  
Vol 46 (38) ◽  
pp. 12785-12789 ◽  
Author(s):  
C. Lu ◽  
K. Laws ◽  
A. Eskandari ◽  
K. Suntharalingam
Keyword(s):  
Reactive Oxygen Species ◽  
Stem Cells ◽  
Schiff Base ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Cancer Cells ◽  
Reactive Oxygen ◽  
Cyclooxygenase 2 ◽  
Oxygen Species

Tetranuclear copper(ii) complexes containing multiple diclofenac and Schiff base moieties,1–4, are shown to kill bulk cancer cells and cancer stem cells (CSCs) with low micromolar potency.

scholarly journals Rejuvenation of mesenchymal stem cells by extracellular vesicles inhibits the elevation of reactive oxygen species

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Vuong Cat Khanh ◽  
Toshiharu Yamashita ◽  
Kinuko Ohneda ◽  
Chiho Tokunaga ◽  
Hideyuki Kato ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Cellular Senescence ◽  
Skin Flap ◽  
Reactive Oxygen ◽  
Oxygen Species

Abstract Aging induces numerous cellular disorders, such as the elevation of reactive oxygen species (ROS), in a number type of cells, including mesenchymal stem cells (MSCs). However, the correlation of ROS and impaired healing abilities as well as whether or not the inhibition of elevating ROS results in the rejuvenation of elderly MSCs is unclear. The rejuvenation of aged MSCs has thus recently received attention in the field of regenerative medicine. Specifically, extracellular vesicles (EVs) act as a novel tool for stem cell rejuvenation due to their gene transfer ability with systemic effects and safety. In the present study, we examined the roles of aging-associated ROS in the function and rejuvenation of elderly MSCs by infant EVs. The data clearly showed that elderly MSCs exhibited the downregulation of superoxide dismutase (SOD)1 and SOD3, which resulted in the elevation of ROS and downregulation of the MEK/ERK pathways, which are involved in the impairment of the MSCs’ ability to decrease necrotic area in the skin flap model. Furthermore, treatment with the antioxidant Edaravone or co-overexpression of SOD1 and SOD3 rescued elderly MSCs from the elevation of ROS and cellular senescence, thereby improving their functions. Of note, infant MSC-derived EVs rejuvenated elderly MSCs by inhibiting ROS production and the acceleration of cellular senescence and promoting the proliferation and in vivo functions in both type 1 and type 2 diabetic mice.

scholarly journals Proton beam radiation induces DNA damage and cell apoptosis in glioma stem cells through reactive oxygen species

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
R. Alan Mitteer ◽  
Yanling Wang ◽  
Jennifer Shah ◽  
Sherika Gordon ◽  
Marcus Fager ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Stem Cells ◽  
Dna Damage ◽  
Proton Beam ◽  
Cell Apoptosis ◽  
Reactive Oxygen ◽  
Glioma Stem Cells ◽  
Oxygen Species ◽  
Beam Radiation ◽  
Proton Beam Radiation

scholarly journals Reactive Oxygen Species Are Required for Human Mesenchymal Stem Cells to Initiate Proliferation after the Quiescence Exit

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
O. G. Lyublinskaya ◽  
Ya. G. Borisov ◽  
N. A. Pugovkina ◽  
I. S. Smirnova ◽  
Ju. V. Obidina ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Stem Cells ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Human Mesenchymal Stem Cells ◽  
S Phase ◽  
Oxygen Species ◽  
Antioxidant Treatment

The present study focuses on the involvement of reactive oxygen species (ROS) in the process of mesenchymal stem cells “waking up” and entering the cell cycle after the quiescence. Using human endometrial mesenchymal stem cells (eMSCs), we showed that intracellular basal ROS level is positively correlated with the proliferative status of the cell cultures. Our experiments with the eMSCs synchronized in the G0phase of the cell cycle revealed a transient increase in the ROS level upon the quiescence exit after stimulation of the cell proliferation. This increase was registered before the eMSC entry to the S-phase of the cell cycle, and elimination of this increase by antioxidants (N-acetyl-L-cysteine, Tempol, and Resveratrol) blocked G1–S-phase transition. Similarly, a cell cycle arrest which resulted from the antioxidant treatment was observed in the experiments with synchronized human mesenchymal stem cells derived from the adipose tissue. Thus, we showed that physiologically relevant level of ROS is required for the initiation of human mesenchymal stem cell proliferation and that low levels of ROS due to the antioxidant treatment can block the stem cell self-renewal.

scholarly journals d-amino acid oxidase promotes cellular senescence via the production of reactive oxygen species

2019 ◽  
Vol 2 (1) ◽  
pp. e201800045 ◽  
Author(s):  
Taiki Nagano ◽  
Shunsuke Yamao ◽  
Anju Terachi ◽  
Hidetora Yarimizu ◽  
Haruki Itoh ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Amino Acids ◽  
Dna Damage ◽  
Amino Acid ◽  
Cellular Senescence ◽  
Reactive Oxygen ◽  
Acid Oxidase ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Amino Acid Oxidase

d-amino acid oxidase (DAO) is a flavin adenine dinucleotide (FAD)–dependent oxidase metabolizing neutral and polard-amino acids. Unlikel-amino acids, the amounts ofd-amino acids in mammalian tissues are extremely low, and therefore, little has been investigated regarding the physiological role of DAO. We have recently identifiedDAOto be up-regulated in cellular senescence, a permanent cell cycle arrest induced by various stresses, such as persistent DNA damage and oxidative stress. Because DAO produces reactive oxygen species (ROS) as byproducts of substrate oxidation and the accumulation of ROS mediates the senescence induction, we explored the relationship between DAO and senescence. We found that inhibition of DAO impaired senescence induced by DNA damage, and ectopic expression of wild-type DAO, but not enzymatically inactive mutant, enhanced it in an ROS-dependent manner. Furthermore, addition ofd-amino acids and riboflavin, a metabolic precursor of FAD, to the medium potentiated the senescence-promoting effect of DAO. These results indicate that DAO promotes senescence through the enzymatic ROS generation, and its activity is regulated by the availability of its substrate and coenzyme.

scholarly journals The ESCRT protein CHMP5 restrains skeletal progenitor cell senescence by preserving endo-lysosomal-mitochondrial network

2020 ◽  
Author(s):  
Xianpeng Ge ◽  
Lizhi He ◽  
Haibo Liu ◽  
Cole M. Haynes ◽  
Jae-Hyuck Shim
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Dna Damage ◽  
Progenitor Cell ◽  
Joint Stiffness ◽  
Cell Senescence ◽  
Endocytic Pathway ◽  
Skeletal Growth ◽  
Oxygen Species ◽  
Mitochondrial Network

AbstractThe endocytic pathway actively interacts with mitochondria in maintaining cellular homeostasis. However, how the dysfunction of this inter-organelle interaction causing pathological outcomes remains less understood. Here we show that an aberrant endocytic pathway from the deficiency of CHMP5 in skeletal progenitor cells causes accumulation of functionally compromised mitochondria, which induce cellular senescence via reactive oxygen species (ROS)-mediated oxidative stress and DNA damage. These senescent progenitors can lead to distorted skeletal growth via a combination of cell-autonomous and non-autonomous mechanisms. Consequently, mice lacking Chmp5 in Ctsk-expressing periskeletal progenitors or Dmp1-expressing musculoskeletal progenitors develop multiple skeletal/muscular abnormalities, including robust bone overgrowth, progressive joint stiffness, and myopathy. Targeting senescent cells using senolytic drugs significantly alleviates these lesions and improves animal motility. Overall, our results reveal that CHMP5 restricts skeletal progenitor cell senescence through maintaining the endo-lysosomal-mitochondrial network and cell senescence represents a yet unexplored mechanism for detrimental alterations from the perturbed organelle network.

scholarly journals Proteome and Secretome Dynamics of Stem Cell-Derived Retinal Pigmented Epithelium in Response to Acute and Chronic ROS

2019 ◽  
Author(s):  
Jesse G. Meyer ◽  
Thelma Garcia ◽  
Birgit Schilling ◽  
Bradford W. Gibson ◽  
Deepak A. Lamba
Keyword(s):  
Reactive Oxygen Species ◽  
Stem Cell ◽  
Molecular Mechanisms ◽  
Reactive Oxygen ◽  
Age Related Macular Degeneration ◽  
Oxygen Species ◽  
Urotensin Ii ◽  
Retinal Pigmented Epithelium ◽  
Age Related ◽  
Pigmented Epithelium

AbstractAge-related macular degeneration (AMD) is the leading cause of blindness in developed countries, and is characterized by slow retinal degeneration linked to chronic oxidative stress in the retinal pigmented epithelium (RPE). The exact molecular mechanisms that lead to RPE death and dysfunction in response to chronic reactive oxygen species (ROS) are still unclear. In this work, human stem cell-derived RPE samples were treated with a low dose of paraquat (PQ) for 1 week or 3 weeks to induce chronic reactive oxygen species (ROS) stress. Cells were then harvested and both the intracellular and secreted RPE proteomes were quantified by mass spectrometry. Inside the RPE, chronic ROS caused concerted increase of glycolytic proteins but decreased mitochondrial proteins, as well as decreased extracellular matrix proteins and membrane proteins required for endocytosis. From the secreted proteins, we found that stressed RPE secrete over 1,000 detectable proteins, and the composition of the proteins secreted from RPE changes due to chronic ROS. Notably, secreted APOE is decreased 4-fold due to 3 weeks of chronic ROS stress, and urotensin-II, the strongest known vasoconstrictor, doubles. Further, secreted TGF-beta is increased, and its cognate signaler BMP1 decreased in the secretome. Together, these alterations of the RPE proteome and protein secretome paint a detailed molecular picture of the retinal stress response in space and time.

scholarly journals The Role ofHibiscus sabdariffaL. (Roselle) in Maintenance ofEx VivoMurine Bone Marrow-Derived Hematopoietic Stem Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Zariyantey Abdul Hamid ◽  
Winnie Hii Lin Lin ◽  
Basma Jibril Abdalla ◽  
Ong Bee Yuen ◽  
Elda Surhaida Latif ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Stem Cells ◽  
Bone Marrow ◽  
Dna Damage ◽  
Ex Vivo ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Sod Activity ◽  
Hematopoietic Stem ◽  
Murine Bone Marrow

Hematopoietic stem cells- (HSCs-) based therapy requiresex vivoexpansion of HSCs prior to therapeutic use. However,ex vivoculture was reported to promote excessive production of reactive oxygen species (ROS), exposing HSCs to oxidative damage. Efforts to overcome this limitation include the use of antioxidants. In this study, the role ofHibiscus sabdariffaL. (Roselle) in maintenance of cultured murine bone marrow-derived HSCs was investigated. Aqueous extract of Roselle was added at varying concentrations (0–1000 ng/mL) for 24 hours to the freshly isolated murine bone marrow cells (BMCs) cultures. Effects of Roselle on cell viability, reactive oxygen species (ROS) production, glutathione (GSH) level, superoxide dismutase (SOD) activity, and DNA damage were investigated. Roselle enhanced the survival(P<0.05)of BMCs at 500 and 1000 ng/mL, increased survival of Sca-1+cells (HSCs) at 500 ng/mL, and maintained HSCs phenotype as shown from nonremarkable changes of surface marker antigen (Sca-1) expression in all experimental groups. Roselle increased(P<0.05)the GSH level and SOD activity but the level of reactive oxygen species (ROS) was unaffected. Moreover, Roselle showed significant cellular genoprotective potency against H2O2-induced DNA damage. Conclusively, Roselle shows novel property as potential supplement and genoprotectant against oxidative damage to cultured HSCs.

scholarly journals Kinetic Modeling Reveals the Roles of Reactive Oxygen Species Scavenging and DNA Repair Processes in Shaping the Dose-Response Curve of KBrO3-Induced DNA Damage

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Maria A. Spassova ◽  
David J. Miller ◽  
Alexander S. Nikolov
Keyword(s):  
Reactive Oxygen Species ◽  
Dna Damage ◽  
Dna Repair ◽  
Base Excision Repair ◽  
Dose Response ◽  
Excision Repair ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Repair Processes ◽  
Base Excision

We have developed a kinetic model to investigate how DNA repair processes and scavengers of reactive oxygen species (ROS) can affect the dose-response shape of prooxidant induced DNA damage. We used as an example chemicalKBrO3which is activated by glutathione and forms reactive intermediates that directly interact with DNA to form 8-hydroxy-2-deoxyguanosine DNA adducts (8-OH-dG). The single strand breaks (SSB) that can result from failed base excision repair of these adducts were considered as an effect downstream from 8-OH-dG. We previously demonstrated that, in the presence of effective base excision repair, 8-OH-dG can exhibit threshold-like dose-response dependence, while the downstream SSB can still exhibit a linear dose-response. Here we demonstrate that this result holds for a variety of conditions, including low levels of GSH, the presence of additional SSB repair mechanisms, or a scavenger. It has been shown that melatonin, a terminal scavenger, inhibitsKBrO3-caused oxidative damage. Our modeling revealed that sustained exposure toKBrO3can lead to fast scavenger exhaustion, in which case the dose-response shapes for both endpoints are not substantially affected. The results are important to consider when forming conclusions on a chemical’s toxicity dose dependence based on the dose-response of early genotoxic events.

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