scholarly journals Dual Role of ROS as Signal and Stress Agents: Iron Tips the Balance in favor of Toxic Effects

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Elena Gammella ◽  
Stefania Recalcati ◽  
Gaetano Cairo

Iron is essential for life, while also being potentially harmful. Therefore, its level is strictly monitored and complex pathways have evolved to keep iron safely bound to transport or storage proteins, thereby maintaining homeostasis at the cellular and systemic levels. These sequestration mechanisms ensure that mildly reactive oxygen species like anion superoxide and hydrogen peroxide, which are continuously generated in cells living under aerobic conditions, keep their physiologic role in cell signaling while escaping iron-catalyzed transformation in the highly toxic hydroxyl radical. In this review, we describe the multifaceted systems regulating cellular and body iron homeostasis and discuss how altered iron balance may lead to oxidative damage in some pathophysiological settings.

2020 ◽  
Vol 21 (5) ◽  
pp. 477-498
Author(s):  
Yongfeng Chen ◽  
Xingjing Luo ◽  
Zhenyou Zou ◽  
Yong Liang

Reactive oxygen species (ROS), an important molecule inducing oxidative stress in organisms, play a key role in tumorigenesis, tumor progression and recurrence. Recent findings on ROS have shown that ROS can be used to treat cancer as they accelerate the death of tumor cells. At present, pro-oxidant drugs that are intended to increase ROS levels of the tumor cells have been widely used in the clinic. However, ROS are a double-edged sword in the treatment of tumors. High levels of ROS induce not only the death of tumor cells but also oxidative damage to normal cells, especially bone marrow hemopoietic cells, which leads to bone marrow suppression and (or) other side effects, weak efficacy of tumor treatment and even threatening patients’ life. How to enhance the killing effect of ROS on tumor cells while avoiding oxidative damage to the normal cells has become an urgent issue. This study is a review of the latest progress in the role of ROS-mediated programmed death in tumor treatment and prevention and treatment of oxidative damage in bone marrow induced by ROS.


Planta ◽  
2009 ◽  
Vol 231 (2) ◽  
pp. 221-231 ◽  
Author(s):  
Ladislav Tamás ◽  
Igor Mistrík ◽  
Jana Huttová ◽  
L’ubica Halušková ◽  
Katarína Valentovičová ◽  
...  

2003 ◽  
Vol 9 (5) ◽  
pp. 339-346 ◽  
Author(s):  
Nalin Siriwardhana ◽  
K.-W. Lee ◽  
Y.-J. Jeon ◽  
S.-H. Kim ◽  
J.-W. Haw

Water and organic extracts (diethyl ether, chloroform, ethyl acetate, acetone, ethanol and methanol) obtained from Hizikia fusiformis were screened on reactive oxygen species (ROS) scavenging assays (1,1-diphenyl-2-picrylhydrazyl (DPPH), superoxide anion, hydrogen peroxide and hydroxyl radical) and lipid peroxidation (inhibition of linoleic acid oxidation) inhibitory assays. Water, methanol and ethanol extracts showed significant ROS radical scavenging activities. Water extracts showed high scavenging activities on hydrogen peroxide (around 76%) and DPPH radicals (around 75%) while it presented a moderate scavenging activity on hydroxyl radicals (around 54%). Comparatively higher ROS scavenging activities were recorded in hydroxyl radical and DPPH scavenging assays. DPPH radical scavenging activities were well correlated with the polyphenolic content. ROS scavenging and lipid peroxidation inhibition activities indicated that H. fusiformis might be a valuable natural antioxidative source containing both water and fatsoluble antioxidative components.


2008 ◽  
Vol 44 (7) ◽  
pp. 1295-1304 ◽  
Author(s):  
Anuradha P. Goud ◽  
Pravin T. Goud ◽  
Michael P. Diamond ◽  
Bernard Gonik ◽  
Husam M. Abu-Soud

2021 ◽  
Author(s):  
Qingda Wang ◽  
Zhigang Chen ◽  
Xi Zhang ◽  
Yuping Xin ◽  
Yongzhen Xia ◽  
...  

During aerobic respiration, mitochondria generate superoxide anion (O2&middot−), hydrogen peroxide (H2O2), and hydroxyl radical (HO·), and these reactive oxygen species (ROS) are detrimental to mitochondria. Mitochondrial damage is linked to a broad spectrum of pathologies such as Alzheimer's disease, hemochromatosis, and diabetes. Mitochondria contain several enzymes for rapidly removing superoxide anion and hydrogen peroxide, but how they antagonize HO· is elusive, representing a loophole in the anti-ROS system. Herein, we discovered that Rhodanese 2 (Rdl2) is critical for maintaining the functionality and integrity of mitochondria under sub-lethal ROS stress in Saccharomyces cerevisiae. Rdl2 converts stable sulfur species (thiosulfate and dialkyl polysulfide) to reactive sulfane sulfur including persulfide that protects mitochondrial DNA via scavenging HO·. Surprisingly, hydrogen sulfide (H2S) promotes HO· production through stimulating the Fenton reaction, leading to increased DNA damage. Our study may reveal an ex-ante mean for antagonizing HO·, patching the loophole of the anti-ROS system in mitochondria.


2018 ◽  
Vol 115 (30) ◽  
pp. 7765-7770 ◽  
Author(s):  
Wei Li ◽  
Jessica F. Young ◽  
Jianjun Sun

Ovarian reactive oxygen species (ROS) are believed to regulate ovulation in mammals, but the details of ROS production in follicles and the role of ROS in ovulation in other species remain underexplored. In Drosophila ovulation, matrix metalloproteinase 2 (MMP2) is required for follicle rupture by degradation of posterior follicle cells surrounding a mature oocyte. We recently demonstrated that MMP2 activation and follicle rupture are regulated by the neuronal hormone octopamine (OA) and the octopamine receptor in mushroom body (OAMB). In the current study, we investigated the role of the superoxide-generating enzyme NADPH oxidase (NOX) in Drosophila ovulation. We report that Nox is highly enriched in mature follicle cells and that Nox knockdown in these cells leads to a reduction in superoxide and to defective ovulation. Similar to MMP2 activation, NOX enzymatic activity is also controlled by the OA/OAMB-Ca2+ signaling pathway. In addition, we report that extracellular superoxide dismutase 3 (SOD3) is required to convert superoxide to hydrogen peroxide, which acts as the key signaling molecule for follicle rupture, independent of MMP2 activation. Given that Nox homologs are expressed in mammalian follicles, the NOX-dependent hydrogen peroxide signaling pathway that we describe could play a conserved role in regulating ovulation in other species.


2007 ◽  
Vol 293 (3) ◽  
pp. H1969-H1977 ◽  
Author(s):  
Iwan A. Williams ◽  
David G. Allen

Duchenne muscular dystrophy (DMD) is caused by deficiency of the cytoskeletal protein dystrophin. Oxidative stress is thought to contribute to the skeletal muscle damage in DMD; however, little is known about the role of oxidative damage in the pathogenesis of the heart failure that occurs in DMD patients. The dystrophin-deficient ( mdx) mouse is an animal model of DMD that also lacks dystrophin. The current study investigates the role of the antioxidant N-acetylcysteine (NAC) on mdx cardiomyocyte function, Ca2+ handling, and the cardiac inflammatory response. Treated mice received 1% NAC in their drinking water for 6 wk. NAC had no effect on wild-type (WT) mice. Immunohistochemistry experiments revealed that mdx mice had increased dihydroethidine (DHE) staining, an indicator of superoxide production; NAC-treatment reduced DHE staining in mdx hearts. NAC treatment attenuated abnormalities in mdx cardiomyocyte Ca2+ handling. Mdx cardiomyocytes had decreased fractional shortening and decreased Ca2+ sensitivity; NAC treatment returned mdx fractional shortening to WT values but did not affect the Ca2+ sensitivity. Immunohistochemistry experiments revealed that mdx hearts had increased levels of collagen type III and the macrophage-specific protein, CD68; NAC-treatment returned collagen type III and CD68 expression close to WT values. Finally, mdx hearts had increased NADPH oxidase activity, suggesting it could be a possible source of increased reactive oxygen species in mdx mice. This study is the first to demonstrate that oxidative damage may be involved in the pathogenesis of the heart failure that occurs in mdx mice. Therapies designed to reduce oxidative damage might be beneficial to DMD patients with heart failure.


Reproduction ◽  
2020 ◽  
Vol 159 (4) ◽  
pp. 423-436 ◽  
Author(s):  
Ayelen Moreno-Irusta ◽  
Esteban M Dominguez ◽  
Clara I Marín-Briggiler ◽  
Arturo Matamoros-Volante ◽  
Ornella Lucchesi ◽  
...  

Sperm chemotaxis may facilitate the finding of the oocyte. Only capacitated spermatozoa can orient their movement by chemotaxis, which as well as capacitation, is regulated in part by the cAMP-PKA pathway. Reactive oxygen species (ROS) are produced during sperm capacitation which is closely related to chemotaxis. Then, the ROS participation in the chemotactic signaling can be expected. Here we studied the role of ROS in the chemotaxis signaling of equine spermatozoa which produce high quantities of ROS because of their energy metabolism. The level of capacitated and chemotactic spermatozoa was increased with 0.1 and 0.2 mM hydrogen peroxide (H2O2), which was involved in the chemotactic signaling. By combining a concentration gradient of H2O2 with inhibitors/chelators of some of the signaling pathway elements, we showed that the activation of NOX (membrane NADPH oxidase) increases the intracellular ROS which activate the chemotaxis AMPc-PKA pathway. Our results provide evidence about the participation of ROS in the chemotactic signaling mediated by progesterone (P).


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