Butein induces cellular senescence through reactive oxygen species‐mediated p53 activation in osteosarcoma U‐2 OS cells

2020 ◽  
Author(s):  
Yung‐Ken Hsu ◽  
Hsuan‐Ying Chen ◽  
Chia‐Chieh Wu ◽  
Ying‐Chih Huang ◽  
Cheng‐Pu Hsieh ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cellular Senescence ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
P53 Activation

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 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 Cr(VI) induces mitochondrial-mediated and caspase-dependent apoptosis through reactive oxygen species-mediated p53 activation in JB6 Cl41 cells

2010 ◽  
Vol 245 (2) ◽  
pp. 226-235 ◽  
Author(s):  
Young-Ok Son ◽  
J. Andrew Hitron ◽  
Xin Wang ◽  
Qingshan Chang ◽  
Jingju Pan ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
P53 Activation

IGF-I enhances cellular senescence via the reactive oxygen species–p53 pathway

2012 ◽  
Vol 425 (2) ◽  
pp. 478-484 ◽  
Author(s):  
Anastasia-Evi Handayaningsih ◽  
Michiko Takahashi ◽  
Hidenori Fukuoka ◽  
Genzo Iguchi ◽  
Hitoshi Nishizawa ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cellular Senescence ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
P53 Pathway ◽  
Igf I

scholarly journals p53 Initiates Apoptosis by Transcriptionally Targeting the Antiapoptotic Protein ARC

2007 ◽  
Vol 28 (2) ◽  
pp. 564-574 ◽  
Author(s):  
Yu-Zhen Li ◽  
Dao-Yuan Lu ◽  
Wei-Qi Tan ◽  
Jian-Xun Wang ◽  
Pei-Feng Li
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Apoptotic Pathway ◽  
P53 Expression ◽  
Antiapoptotic Protein ◽  
N Terminus ◽  
P53 Activation

ABSTRACT p53 plays an important role in regulating apoptosis. However, the molecular mechanism by which it initiates the apoptotic program still remains to be fully understood. Here, we report that p53 can transcriptionally target the antiapoptotic protein, apoptosis repressor with caspase recruitment domain (ARC). Our results show that reactive oxygen species and anoxia lead to the up-regulation of p53 expression. Concomitantly, ARC is down-regulated at both the protein and mRNA levels. Knockdown of p53 expression can attenuate the decreases in ARC protein and mRNA levels, indicating that ARC down-regulation is a consequence of p53 activation. Strikingly, p53-induced ARC repression occurs in a transcription-dependent manner. We further demonstrate that the p53 up-regulated modulator of apoptosis (PUMA) and Bad are up-regulated in response to the stimulation with reactive oxygen species or anoxia, and p53 is responsible for their up-regulation. ARC can interact with PUMA or Bad via its N terminus. Such an interaction displaces the association of PUMA or Bad with Bcl-2. ARC repression by p53 leads to its failure to counteract the proapoptotic activity of PUMA and Bad. Thus, our data reveal a novel p53 apoptotic pathway in which it initiates apoptosis by transcriptionally repressing ARC.

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