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.

Why is d-serine nephrotoxic and α-aminoisobutyric acid protective?

2007 ◽  
Vol 293 (1) ◽  
pp. F382-F390 ◽  
Author(s):  
Alexander W. Krug ◽  
Katharina Völker ◽  
William H. Dantzler ◽  
Stefan Silbernagl
Keyword(s):  
Reactive Oxygen Species ◽  
Amino Acid ◽  
Reactive Oxygen ◽  
Proximal Tubules ◽  
Tubular Damage ◽  
Acid Oxidase ◽  
Oxygen Species ◽  
Amino Acid Oxidase ◽  
Aminoisobutyric Acid ◽  
Serine Metabolism

d-Serine selectively causes necrosis of S3 segments of proximal tubules in rats. This leads to aminoaciduria and glucosuria. Coinjection of the nonmetabolizable amino acid α-aminoisobutyric acid (AIB) prevents the tubulopathy. d-serine is selectively reabsorbed in S3, thereby gaining access to peroxisomal d-amino acid oxidase (d-AAO). d-AAO-mediated metabolism produces reactive oxygen species. We determined the fractional excretion of amino acids and glucose in rats after intraperitoneal injection of d-serine alone or together with reduced glutathione (GSH) or AIB. Both compounds prevented the hyperaminoaciduria. We measured GSH concentrations in renal tissue before (control) and after d-serine injection and found that GSH levels decreased to ∼30% of control. This decrease was prevented when equimolar GSH was coinjected with d-serine. To find out why AIB protected the tubule from d-serine toxicity, we microinfused d-[14C]serine or [14C]AIB (0.36 mmol/l) together with [3H]inulin in late proximal tubules in vivo and measured the radioactivity in the final urine. Fractional reabsorption of d-[14C]serine and [14C]AIB amounted to 55 and 70%, respectively, and 80 mmol/l of AIB or d-serine mutually prevented reabsorption to a great extent. d-AAO activity measured in vitro (using d-serine as substrate) was not influenced by a 10-fold higher AIB concentration. We conclude from these results that 1) d-AAO-mediated d-serine metabolism lowers renal GSH concentrations and thereby provokes tubular damage because reduction of reactive oxygen species by GSH is diminished and 2) AIB prevents d-serine-induced tubulopathy by inhibition of d-serine uptake in S3 segments rather than by interfering with intracellular d-AAO-mediated d-serine metabolism.

scholarly journals Candida albicans Induces Arginine Biosynthetic Genes in Response to Host-Derived Reactive Oxygen Species

2012 ◽  
Vol 12 (1) ◽  
pp. 91-100 ◽  
Author(s):  
Claudia Jiménez-López ◽  
John R. Collette ◽  
Kimberly M. Brothers ◽  
Kelly M. Shepardson ◽  
Robert A. Cramer ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Candida Albicans ◽  
Amino Acid ◽  
Reactive Oxygen ◽  
Single Amino Acid ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Biosynthetic Genes ◽  
Content Type

ABSTRACTThe interaction ofCandida albicanswith phagocytes of the host's innate immune system is highly dynamic, and its outcome directly impacts the progression of infection. While the switch to hyphal growth within the macrophage is the most obvious physiological response, much of the genetic response reflects nutrient starvation: translational repression and induction of alternative carbon metabolism. Changes in amino acid metabolism are not seen, with the striking exception of arginine biosynthesis, which is upregulated in its entirety during coculture with macrophages. Using single-cell reporters, we showed here that arginine biosynthetic genes are induced specifically in phagocytosed cells. This induction is lower in magnitude than during arginine starvationin vitroand is driven not by an arginine deficiency within the phagocyte but instead by exposure to reactive oxygen species (ROS). Curiously, these genes are induced in a narrow window of sublethal ROS concentrations.C. albicanscells phagocytosed by primary macrophages deficient in thegp91phoxsubunit of the phagocyte oxidase do not express theARGpathway, indicating that the induction is dependent on the phagocyte oxidative burst.C. albicans argpathway mutants are retarded in germ tube and hypha formation within macrophages but are not notably more sensitive to ROS. We also find that theARGpathway is regulated not by the general amino acid control response but by transcriptional regulators similar to theSaccharomyces cerevisiaeArgR complex. In summary, phagocytosis induces this single amino acid biosynthetic pathway in an ROS-dependent manner.

scholarly journals Lipopolysaccharide Enhances Genotoxicity by Activating GADD45G and NF-κB in Human Corneal Epithelial Cells

2022 ◽  
Vol 2022 ◽  
pp. 1-14
Author(s):  
Ramachandran Samivel ◽  
Umadevi Subramanian ◽  
Adnan Ali Khan ◽  
Omar Kirat ◽  
Ali Masmali ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Dna Damage ◽  
Epithelial Cells ◽  
Mitochondrial Membrane ◽  
Reactive Oxygen ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Corneal Epithelial Cells ◽  
Corneal Epithelial ◽  
Human Corneal Epithelial Cells

As the prevalence of microbial keratitis increases, it creates an environment conducive to genotoxicity response. A potential connection between growth arrest and DNA-damage-inducible 45 gamma (GADD45G) gene expression has not been proven in the corneal epithelial cells. The aim of this study was to determine whether lipopolysaccharide (LPS) enhances genotoxicity, DNA damage, and inflammatory responses in human corneal epithelial cells (HCECs) in vitro. In a set of parameters, cytotoxicity, reactive oxygen species, mitochondrial membrane potential, DNA damage, inflammatory response, and apoptosis were assessed. LPS (1, 5, and 10 μg/mL) treated HCECs were increased reactive oxygen species formation, mitochondrial membrane depolarization, and genotoxicity in a concentration-dependent manner. Similarly, NF-κB, PARP1, and TP53 were also overexpressed in the LPS treated HCECs. 24 hours after LPS induction, micronucleus scoring, and proapoptotic factors were also increased. Among them, the GADD45G, NF-κB, and γH2AX were overexpressed both on the mRNA and protein levels in LPS (10 μg/mL) treated HCECs. In our study, we show that the GADD45G signaling can trigger genotoxic instability in HCECs exposed to LPS. Therefore, understanding the factors contributing to infectious keratitis, such as GADD45G, NF-κB, and γH2AX signaling, may help to develop antigenotoxic and anti-inflammatory therapies for corneal dystrophy and epithelial cell remodeling.

scholarly journals Reactive Oxygen Species-Mediated Cytotoxicity in Liver Carcinoma Cells Induced by Silver Nanoparticles Biosynthesized Using Schinus molle Extract

Nanomaterials ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 161
Author(s):  
Waleed Ali Hailan ◽  
Khalid Mashay Al-Anazi ◽  
Mohammad Abul Farah ◽  
Mohammad Ajmal Ali ◽  
Ahmed Ali Al-Kawmani ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Dna Damage ◽  
Silver Nanoparticles ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Liver Carcinoma ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Schinus Molle ◽  
Biosynthesized Agnps

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is ranked as the third most common cause of cancer-related mortality worldwide. Schinus molle (S. mole) L. is an important medicinal plant that contains many bioactive compounds with pharmacological properties. The role of S. molle leaf extract in the biosynthesis of silver nanoparticles (AgNPs) was determined. The biosynthesized AgNPs were thoroughly characterized by UV–vis spectrophotometry, transmission electron microscopy (TEM), X-ray diffraction (XRD), and dynamic light scattering (DLS) techniques. Furthermore, the cytotoxic effect of the biosynthesized AgNPs using S. molle (SMAgNPs) against HepG2 liver cancer cells was investigated. Reactive oxygen species generation, apoptosis induction, DNA damage, and autophagy activity were analyzed. The results clearly showed that the biosynthesized silver nanoparticles inhibited the proliferation of HepG2 by significantly (p < 0.05) inducing oxidative stress, cytotoxicity, DNA damage, apoptosis, and autophagy in a dose- and time-dependent manner. These findings may encourage integrating the potential of natural products and the efficiency of silver nanoparticles for the fabrication of safe, environmentally friendly, and effective anticancer agents.

scholarly journals Biological role of D-amino acid oxidase and D-aspartate oxidase. Effects of D-amino acids.

1993 ◽  
Vol 268 (36) ◽  
pp. 26941-26949
Author(s):  
A D'Aniello ◽  
G D'Onofrio ◽  
M Pischetola ◽  
G D'Aniello ◽  
A Vetere ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Biological Role ◽  
Acid Oxidase ◽  
Amino Acid Oxidase

scholarly journals PAC1 regulates receptor tyrosine kinase transactivation in a reactive oxygen species-dependent manner

Peptides ◽  
2019 ◽  
Vol 120 ◽  
pp. 170017
Author(s):  
Terry W. Moody ◽  
Lingaku Lee ◽  
Tatiana Iordanskaia ◽  
Irene Ramos-Alvarez ◽  
Paola Moreno ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Reactive Oxygen ◽  
Dependent Manner ◽  
Oxygen Species
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