scholarly journals Reactive oxygen species may influence on the crossroads of stemness, senescence, and carcinogenesis in a cell via the roles of APRO family proteins

Author(s):  
Yuka Ikeda ◽  
Kurumi Taniguchi ◽  
Nozomi Nagase ◽  
Ai Tsuji ◽  
Yasuko Kitagishi ◽  
...  

Excessive reactive oxygen species (ROS) may cause oxidative stress which is involved in aging and in the pathogenesis of various human diseases. Whereas unregulated levels of the ROS may be harmful, regulated basal level of ROS are even necessary to support cellular functions as a second messenger for homeostasis under physiological conditions. Therefore, redox medicine could develop as a new therapeutic concept for human health-benefits. Here, we introduce the involvement of ROS on the crossroads of stemness, senescence, and carcinogenesis in a stem cell and cancer cell biology. Amazingly, the anti-proliferative (APRO) family anti-proliferative proteins characterized by immediate early growth responsive genes may also be involved in the crossroads machinery. The biological functions of APRO proteins (APROs) seem to be quite intricate, however, which might be a key modulator of microRNAs (miRNAs). Given the crucial roles of ROS and APROs for pathophysiological functions, upcoming novel therapeutics should include vigilant modulation of the redox state. Next generation of medicine including regenerative medicine and/or cancer therapy will likely comprise strategies for altering the redox environment with the APROs via the modulation of miRNAs as well as with the regulation of ROS of cells in a sustainable manner.

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e82834 ◽  
Author(s):  
Fumihiko Yoshino ◽  
Ayaka Yoshida ◽  
Atsushi Nakajima ◽  
Satoko Wada-Takahashi ◽  
Shun-suke Takahashi ◽  
...  

Reproduction ◽  
2013 ◽  
Vol 145 (5) ◽  
pp. 471-478 ◽  
Author(s):  
S Morado ◽  
P Cetica ◽  
M Beconi ◽  
J G Thompson ◽  
G Dalvit

The knowledge concerning redox and reactive oxygen species (ROS)-mediated regulation of early embryo development is scarce and remains controversial. The aim of this work was to determine ROS production and redox state during early in vitro embryo development in sperm-mediated and parthenogenetic activation of bovine oocytes. Sperm-mediated oocyte activation was carried out in IVF-modified synthetic oviductal fluid (mSOF) with frozen–thawed semen. Parthenogenetic activation was performed in TALP plus ionomycin and then in IVF-mSOF with 6-dimethylaminopurine plus cytochalasin B. Embryos were cultured in IVF-mSOF. ROS and redox state were determined at each 2-h interval (7–24 h from activation) by 2′,7′-dichlorodihydrofluorescein diacetate and RedoxSensor Red CC-1 fluorochromes respectively. ROS levels and redox state differed between activated and non-activated oocytes (P<0.05 by ANOVA). In sperm-activated oocytes, an increase was observed between 15 and 19 h (P<0.05). Conversely, in parthenogenetically activated oocytes, we observed a decrease at 9 h (P<0.05). In sperm-activated oocytes, ROS fluctuated throughout the 24 h, presenting peaks around 7, 19, and 24 h (P<0.05), while in parthenogenetic activation, peaks were detected at 7, 11, and 17 h (P<0.05). In the present work, we found clear distinctive metabolic patterns between normal and parthenogenetic zygotes. Oxidative activity and ROS production are an integral part of bovine zygote behavior, and defining a temporal pattern of change may be linked with developmental competence.


2010 ◽  
Vol 298 (1) ◽  
pp. F158-F166 ◽  
Author(s):  
Jinu Kim ◽  
Hee-Seong Jang ◽  
Kwon Moo Park

Ischemic preconditioning by a single event of ischemia and reperfusion (SIRPC) dramatically protects renal function against ischemia and reperfusion (I/R) induced several weeks later. We recently reported that reactive oxygen species (ROS) and oxidative stress were sustained in a kidney that had functionally recovered from I/R injury, thus suggesting an association between SIRPC and ROS and oxidative stress. However, the role of ROS in SIRPC remains to be clearly elucidated. To assess the involvement of ROS in SIRPC, mice were subjected to SIRPC (30 min of bilateral renal ischemia and 8 days of reperfusion) and then exposed to I/R injury. Thirty minutes of bilateral renal ischemia in the non-SIRPC mice resulted in a marked increase in plasma creatinine levels 4 and 24 h after reperfusion, which was not observed in the I/R in the SIRPC mice. SIRPC resulted in increases in the levels of kidney superoxide. Administrations of manganese(III) tetrakis(1-methyl-4-pyridyl) porphyrin [MnTMPyP; a cell-permeable superoxide dismutase (SOD) mimetic] and N-acetylcysteine (NAc; a ROS scavenger) to SIRPC mice blocked the SIRPC-induced increase in superoxide levels and removed ∼48–64% of the functional protection of the SIRPC kidney. Additionally, these administrations significantly inhibited I/R-induced increases in superoxide formation, hydrogen peroxide production, and lipid peroxidation, along with the inhibition of I/R-induced reductions in the expression and activity of manganese SOD, copper-zinc SOD, and catalase. Furthermore, administrations of MnTMPyP or NAc inhibited the SIRPC-induced increase in inducible nitric oxide synthase expression but did not inhibit the SIRPC-induced increases in heat shock protein-25 expression. In conclusion, the renoprotection afforded by SIRPC was triggered by ROS generated by SIRPC.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
An Xie ◽  
He Li ◽  
Yumei Hao ◽  
Yujia Zhang

AbstractThe biological functions and toxic effects of reactive oxygen species (ROS) are generally entangled. A large amount of ROS may cause oxidative damage to cell biomolecules, leading to cell death. Tumor treatment can be carried out by using the toxicity of ROS, and various nanosystems related to ROS have been designed. In fact, the level of active oxygen in the biological microenvironment can be regulated in advanced therapeutics via designed nanoscale engineering, which can open up a new direction of treatment with specific simplicity. In this progress report, the authors first introduced how ROS causes cell death. Then, recent studies on converting the inherent toxicity from ROS into advanced treatment tools are highlighted.


Biomolecules ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 124 ◽  
Author(s):  
Bahare Salehi ◽  
Miquel Martorell ◽  
Jack Arbiser ◽  
Antoni Sureda ◽  
Natália Martins ◽  
...  

The term “antioxidant” is one of the most confusing definitions in biological/medical sciences. In chemistry, “antioxidant” is simply conceived “a compound that removes reactive species, mainly those oxygen-derived”, while in a cell context, the conceptual definition of an antioxidant is poorly understood. Indeed, non-clinically recommended antioxidants are often consumed in large amounts by the global population, based on the belief that cancer, inflammation and degenerative diseases are triggered by high oxygen levels (or reactive oxygen species) and that through blocking reactive species production, organic unbalances/disorders can be prevented and/or even treated. The popularity of these chemicals arises in part from the widespread public mistrust of allopathic medicine. In fact, reactive oxygen species play a dual role in dealing with different disorders, since they may contribute to disease onset and/or progression but may also play a key role in disease prevention. Further, the ability of the most commonly used supplements, such as vitamins C, E, selenium, and herbal supplements to decrease pathologic reactive oxygen species is not clearly established. Hence, the present review aims to provide a nuanced understanding of where current knowledge is and where it should go.


2018 ◽  
Vol 314 (5) ◽  
pp. R667-R683 ◽  
Author(s):  
Marie Erard ◽  
Sophie Dupré-Crochet ◽  
Oliver Nüße

Redox biology has become a major issue in numerous areas of physiology. Reactive oxygen species (ROS) have a broad range of roles from signal transduction to growth control and cell death. To understand the nature of these roles, accurate measurement of the reactive compounds is required. An increasing number of tools for ROS detection is available; however, the specificity and sensitivity of these tools are often insufficient. Furthermore, their specificity has been rarely evaluated in complex physiological conditions. Many ROS probes are sensitive to environmental conditions in particular pH, which may interfere with ROS detection and cause misleading results. Accurate detection of ROS in physiology and pathophysiology faces additional challenges concerning the precise localization of the ROS and the timing of their production and disappearance. Certain ROS are membrane permeable, and certain ROS probes move across cells and organelles. Targetable ROS probes such as fluorescent protein-based biosensors are required for accurate localization. Here we analyze these challenges in more detail, provide indications on the strength and weakness of current tools for ROS detection, and point out developments that will provide improved ROS detection methods in the future. There is no universal method that fits all situations in physiology and cell biology. A detailed knowledge of the ROS probes is required to choose the appropriate method for a given biological problem. The knowledge of the shortcomings of these probes should also guide the development of new sensors.


Blood ◽  
2010 ◽  
Vol 115 (20) ◽  
pp. 4030-4038 ◽  
Author(s):  
Marisa M. Juntilla ◽  
Vineet D. Patil ◽  
Marco Calamito ◽  
Rohan P. Joshi ◽  
Morris J. Birnbaum ◽  
...  

Although AKT is essential for multiple cellular functions, the role of this kinase family in hematopoietic stem cells (HSCs) is unknown. Thus, we analyzed HSC function in mice deficient in the 2 isoforms most highly expressed in the hematopoietic compartment, AKT1 and AKT2. Although loss of either isoform had only a minimal effect on HSC function, AKT1/2 double-deficient HSCs competed poorly against wild-type cells in the development of myeloid and lymphoid cells in in vivo reconstitution assays. Serial transplantations revealed an essential role for AKT1 and AKT2 in the maintenance of long-term HSCs (LT-HSCs). AKT1/2 double-deficient LT-HSCs were found to persist in the G0 phase of the cell cycle, suggesting that the long-term functional defects are caused by increased quiescence. Furthermore, we found that the intracellular content of reactive oxygen species (ROS) is dependent on AKT because double-deficient HSCs demonstrate decreased ROS. The importance of maintaining ROS for HSC differentiation was shown by a rescue of the differentiation defect after pharmacologically increasing ROS levels in double-deficient HSCs. These data implicate AKT1 and AKT2 as critical regulators of LT-HSC function and suggest that defective ROS homeostasis may contribute to failed hematopoiesis.


2000 ◽  
Vol 279 (6) ◽  
pp. L1005-L1028 ◽  
Author(s):  
Victor J. Thannickal ◽  
Barry L. Fanburg

Reactive oxygen species (ROS) are generated as by-products of cellular metabolism, primarily in the mitochondria. When cellular production of ROS overwhelms its antioxidant capacity, damage to cellular macromolecules such as lipids, protein, and DNA may ensue. Such a state of “oxidative stress” is thought to contribute to the pathogenesis of a number of human diseases including those of the lung. Recent studies have also implicated ROS that are generated by specialized plasma membrane oxidases in normal physiological signaling by growth factors and cytokines. In this review, we examine the evidence for ligand-induced generation of ROS, its cellular sources, and the signaling pathways that are activated. Emerging concepts on the mechanisms of signal transduction by ROS that involve alterations in cellular redox state and oxidative modifications of proteins are also discussed.


1996 ◽  
Vol 24 (4) ◽  
pp. 345-351 ◽  
Author(s):  
H Akamatsu ◽  
Y Niwa ◽  
H Sasaki ◽  
Y Matoba ◽  
Y Asada ◽  
...  

The effects of ofloxacin, ciprofloxacin and balofloxacin on the reactive oxygen species (ROS) levels generated by human neutrophils was examined in vitro; ROS generated in a cell-free, xanthine–xanthine oxidase system was also assessed. The species investigated were superoxide radical anion (O2−), hydrogen peroxide (H2O2) and hydroxyl radical (OH·). Both ofloxacin and ciprofloxacin markedly decreased the levels of O2−, H2O2 and OH· generated by human neutrophils. On the other hand, these drugs did not affect any of the ROS examined in the xanthine-xanthine oxidase system. Balofloxacin showed no significant effect on ROS generated by either system. The present study indicates that ofloxacin and ciprofloxacin may exert an anti-inflammatory action by reducing the potent ROS species excessively generated by neutrophils at the sites of inflammation.


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