IFNγ induces oxidative stress, DNA damage and tumor cell senescence via TGFβ/SMAD signaling-dependent induction of Nox4 and suppression of ANT2

Oncogene ◽  
2015 ◽  
Vol 35 (10) ◽  
pp. 1236-1249 ◽  
Author(s):  
S Hubackova ◽  
A Kucerova ◽  
G Michlits ◽  
L Kyjacova ◽  
M Reinis ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Tumor Cell ◽  
Cell Senescence ◽  
Smad Signaling

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 Cellular Senescence in Age-Related Macular Degeneration: Can Autophagy and DNA Damage Response Play a Role?

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Janusz Blasiak ◽  
Malgorzata Piechota ◽  
Elzbieta Pawlowska ◽  
Magdalena Szatkowska ◽  
Ewa Sikora ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Macular Degeneration ◽  
Dna Damage Response ◽  
Cellular Senescence ◽  
Cell Senescence ◽  
Age Related Macular Degeneration ◽  
Rpe Cells ◽  
Age Related ◽  
Damage Response

Age-related macular degeneration (AMD) is the main reason of blindness in developed countries. Aging is the main AMD risk factor. Oxidative stress, inflammation and some genetic factors play a role in AMD pathogenesis. AMD is associated with the degradation of retinal pigment epithelium (RPE) cells, photoreceptors, and choriocapillaris. Lost RPE cells in the central retina can be replaced by their peripheral counterparts. However, if they are senescent, degenerated regions in the macula cannot be regenerated. Oxidative stress, a main factor of AMD pathogenesis, can induce DNA damage response (DDR), autophagy, and cell senescence. Moreover, cell senescence is involved in the pathogenesis of many age-related diseases. Cell senescence is the state of permanent cellular division arrest and concerns only mitotic cells. RPE cells, although quiescent in the retina, can proliferate in vitro. They can also undergo oxidative stress-induced senescence. Therefore, cellular senescence can be considered as an important molecular pathway of AMD pathology, resulting in an inability of the macula to regenerate after degeneration of RPE cells caused by a factor inducing DDR and autophagy. It is too early to speculate about the role of the mutual interplay between cell senescence, autophagy, and DDR, but this subject is worth further studies.

scholarly journals DNA Damage during Reoxygenation Elicits a Chk2-Dependent Checkpoint Response

2006 ◽  
Vol 26 (5) ◽  
pp. 1598-1609 ◽  
Author(s):  
Rachel A. Freiberg ◽  
Ester M. Hammond ◽  
Mary Jo Dorie ◽  
Scott M. Welford ◽  
Amato J. Giaccia
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Tumor Cell ◽  
Solid Tumors ◽  
Ataxia Telangiectasia ◽  
Clonogenic Survival ◽  
Ataxia Telangiectasia Mutated ◽  
Checkpoint Response ◽  
Opening And Closing ◽  
And Oxidative Stress

ABSTRACT Due to the abnormal vasculature of solid tumors, tumor cell oxygenation can change rapidly with the opening and closing of blood vessels, leading to the activation of both hypoxic response pathways and oxidative stress pathways upon reoxygenation. Here, we report that ataxia telangiectasia mutated-dependent phosphorylation and activation of Chk2 occur in the absence of DNA damage during hypoxia and are maintained during reoxygenation in response to DNA damage. Our studies involving oxidative damage show that Chk2 is required for G2 arrest. Following exposure to both hypoxia and reoxygenation, Chk2−/− cells exhibit an attenuated G2 arrest, increased apoptosis, reduced clonogenic survival, and deficient phosphorylation of downstream targets. These studies indicate that the combination of hypoxia and reoxygenation results in a G2 checkpoint response that is dependent on the tumor suppressor Chk2 and that this checkpoint response is essential for tumor cell adaptation to changes that result from the cycling nature of hypoxia and reoxygenation found in solid tumors.

scholarly journals GSE4, a Small Dyskerin- and GSE24.2-Related Peptide, Induces Telomerase Activity, Cell Proliferation and Reduces DNA Damage, Oxidative Stress and Cell Senescence in Dyskerin Mutant Cells

PLoS ONE ◽  
2015 ◽  
Vol 10 (11) ◽  
pp. e0142980 ◽  
Author(s):  
Laura Iarriccio ◽  
Cristina Manguán-García ◽  
Laura Pintado-Berninches ◽  
José Miguel Mancheño ◽  
Antonio Molina ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Proliferation ◽  
Dna Damage ◽  
Telomerase Activity ◽  
Cell Senescence ◽  
Related Peptide ◽  
Mutant Cells

Serum of 8-OHdG as a potential biomarker of oxidative DNA damage in workers exposed to harmful working environments

2020 ◽  
pp. 783-783
Author(s):  
I. A. Umnyagina ◽  
L. A. Strakhova ◽  
T. V. Blinova
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Blood Serum ◽  
Oxidative Dna Damage ◽  
Working Environment ◽  
Working Environments ◽  
Potential Biomarker ◽  
High Level ◽  
Damage Marker

In the blood serum of 70% individuals exposed to harmful factors of the working environment, a high level of oxidative stress and the DNA damage marker 8-Hydroxy-2’-Deoxyguanosine (8-OHdG) were detected.

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