scholarly journals Rhodanese Rdl2 produces reactive sulfur species to scavenge hydroxyl radical and protect mitochondria

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.

2021 ◽  
Author(s):  
Senlin Wang ◽  
Hong-Shuai Wu ◽  
Kai Sun ◽  
Jinzhong Hu ◽  
Fanghui Chen ◽  
...  

Recently, the toxic hydroxyl radical (·OH) has received wide interest in inducing cell apoptosis by increasing the intracellular reactive oxygen species (ROS) levels. Herein, a cationic polymer (MV-PAH) was rationally...


2004 ◽  
Vol 286 (5) ◽  
pp. C1152-C1158 ◽  
Author(s):  
A. McArdle ◽  
J. van der Meulen ◽  
G. L. Close ◽  
D. Pattwell ◽  
H. Van Remmen ◽  
...  

Contractions of skeletal muscles produce increases in concentrations of superoxide anions and activity of hydroxyl radicals in the extracellular space. The sources of these reactive oxygen species are not clear. We tested the hypothesis that, after a demanding isometric contraction protocol, the major source of superoxide and hydroxyl radical activity in the extracellular space of muscles is mitochondrial generation of superoxide anions and that, with a reduction in MnSOD activity, concentration of superoxide anions in the extracellular space is unchanged but concentration of hydroxyl radicals is decreased. For gastrocnemius muscles from adult (6–8 mo old) wild-type ( Sod2+/+) mice and knockout mice heterozygous for the MnSOD gene ( Sod2+/-), concentrations of superoxide anions and hydroxyl radical activity were measured in the extracellular space by microdialysis. A 15-min protocol of 180 isometric contractions induced a rapid, equivalent increase in reduction of cytochrome c as an index of superoxide anion concentrations in the extracellular space of Sod2+/+ and Sod2+/- mice, whereas hydroxyl radical activity measured by formation of 2,3-dihydroxybenzoate from salicylate increased only in the extracellular space of muscles of Sod2+/+ mice. The lack of a difference in increase in superoxide anion concentration in the extracellular space of Sod2+/+ and Sod2+/- mice after the contraction protocol supported the hypothesis that superoxide anions were not directly derived from mitochondria. In contrast, the data obtained suggest that the increase in hydroxyl radical concentration in the extracellular space of muscles from wild-type mice after the contraction protocol most likely results from degradation of hydrogen peroxide generated by MnSOD activity.


2019 ◽  
Vol 6 (12) ◽  
pp. 3734-3744 ◽  
Author(s):  
Hsin-Se Hsieh ◽  
Richard G. Zepp

Increases in the production and applications of graphene oxide (GO), coupled with reports of its toxic effects, are raising concerns about its health and ecological risks.


Nanomaterials ◽  
2018 ◽  
Vol 8 (12) ◽  
pp. 1040 ◽  
Author(s):  
Ya Zhang ◽  
Xiangchun Zhang ◽  
Qing Yuan ◽  
Wenchao Niu ◽  
Chunyu Zhang ◽  
...  

Anticancer metallodrugs that aim to physiological characters unique to tumor microenvironment are expected to combat drug tolerance and side-effects. Recently, owing to the fact that reactive oxygen species’ is closely related to the development of tumors, people are committed to developing metallodrugs with the capacity of improving the level of reactive oxygen species level toinduce oxidative stress in cancer cells. Herein, we demonstrated that peptide templated gold clusters with atomic precision preferably catalyze the transformation of hydrogen peroxide into superoxide anion in oxidative pressure-type tumor cells. Firstly, we successfully constructed gold clusters by rationally designing peptide sequences which targets integrin ανβ3 overexpressed on glioblastoma cells. The superoxide anion, radical derived from hydrogen peroxide and catalyzed by gold clusters, was confirmed in vitro under pseudo-physiological conditions. Then, kinetic parameters were evaluated to verify the catalytic properties of gold clusters. Furthermore, these peptide decorated clusters can serve as special enzyme-like catalyst to convert endogenous hydrogen peroxide into superoxide anion, elevated intracellular reactive oxygen species levels, lower mitochondrial membrane potential, damage biomacromolecules, and trigger tumor cell apoptosis consequently.


2020 ◽  
Vol 56 (68) ◽  
pp. 9779-9782 ◽  
Author(s):  
Aaron M. Fleming ◽  
Cynthia J. Burrows

Fe(ii)-Fenton reaction in bicarbonate buffer yields CO3˙−, not HO˙, oxidizing 2′-deoxyguanosine to yield 8-oxo-7,8-dihydro-2′-deoxyguanosine with no ribose damage.


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.


Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4337
Author(s):  
Maphuti T. Lebelo ◽  
Anna M. Joubert ◽  
Michelle H. Visagie

2-Methoxyestradiol (2ME), a 17β-estradiol metabolite, exerts anticancer properties in vitro and in vivo. To address 2ME’s low bioavailability, research led to the in silico design of sulphamoylated 2ME analogues. However, the role of oxidative stress induced in the activity exerted by sulphamoylated compounds remains elusive. In the current study, the influence of 2-Ethyl-17-oxoestra-1,3,5(10)-trien-3-yl sulphamate (ESE-one) on reactive oxygen species (ROS) induction and its effect on cell proliferation, as well as morphology, were assessed in breast tumorigenic cells (MCF-7 and MDA-MB-231). Fluorescent microscopy showed that sulphamoylated estradiol analogues induced hydrogen peroxide and superoxide anion, correlating with decreased cell growth demonstrated by spectrophotometry data. ESE-one exposure resulted in antiproliferation which was repressed by tiron (superoxide inhibitor), trolox (peroxyl inhibitor) and N,N′-dimethylthiourea (DMTU) (hydrogen peroxide inhibitor). Morphological studies demonstrated that tiron, trolox and DMTU significantly decreased the number of rounded cells and shrunken cells in MCF-7 and MDA-MB-231 cells induced by ESE-one. This in vitro study suggests that ESE-one induces growth inhibition and cell rounding by production of superoxide anion, peroxyl radical and hydrogen peroxide. Identification of these biological changes in cancer cells caused by sulphamoylated compounds hugely contributes towards improvement of anticancer strategies and the ROS-dependent cell death pathways in tumorigenic breast cells.


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.


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