Yin and Yang of Mitochondrial ROS

Starkov, Anatoly A.; Wallace, Kendall B.

doi:10.1142/9781860948046_0001

Cited by 4 publications

(3 citation statements)

References 166 publications

(261 reference statements)

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“…Our TEM and fluorescent microscopy images of Mito tracker/DAPI double staining results, also demonstrate the ultrastructural changes in mitochondrial morphology on ZnO NP‐exposed cells. These changes gradually increased at elevated concentrations of ZnO NPs (1‐20 μg/mL), which hamper the mitochondrial dynamics, prevent cellular bioenergetics and produce mitochondrial ROS due to oxidative stress in cells (Starkov & Wallace, ).…”

Section: Discussionmentioning

confidence: 99%

Zinc oxide nanoparticles induced gene mutation at the HGPRT locus and cell cycle arrest associated with apoptosis in V‐79 cells

Jain

Singh

Dubey

et al. 2019

J of Applied Toxicology

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In recent years, the large‐scale production of ZnO nanoparticles (NPs) for various applications is increasing exponentially and may pose serious health issues when inhaled either during occupational exposure or in consumer settings. The mechanisms underlying the toxicity of NPs have recently been studied intensively. Despite the existing studies, the mutagenicity of ZnO NPs in the eukaryotic system is still unclear. Therefore, the aim of the present study was to investigate the mutagenic potential of ZnO NPs using Chinese hamster lung fibroblast cells (V‐79) as an in‐vitro model. The study has demonstrated a significant uptake of ZnO NPs by flow cytometry with the confirmation of transmission electron microscopy. A reduction in cell viability was observed with a concomitant increase in reactive oxygen species (**P < 0.01, ***P < 0.001) after ZnO NP (1‐20 μg/mL) exposure. Excessive reactive oxygen species can induce oxidative stress, which leads to genotoxic insult, and further gene mutation. Apart from measuring the genotoxicity by Comet assay, a change of 2.84‐fold in the HGPRT gene mutant frequency was observed by the mammalian gene forward mutation assay. All the genotoxicity endpoints such as chromosomal break, DNA damage and mutagenicity were observed at 6 hours of ZnO NP exposure. Our results also showed that ZnO NPs manifested the cell cycle arrest, ultrastructural modifications and further cell death. A significant (**P < 0.01, ***P < 0.001) increase in the apoptotic cells was detected using annexin V‐fluorescein isothiocyanate/propidium iodide double staining by flow cytometry. Our findings presented here clearly stimulate the need for careful regulations of ZnO NPs.

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Section: Discussionmentioning

confidence: 99%

Zinc oxide nanoparticles induced gene mutation at the HGPRT locus and cell cycle arrest associated with apoptosis in V‐79 cells

Jain

Singh

Dubey

et al. 2019

J of Applied Toxicology

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“…Results indicated that capacitation inducers (such as BSA [36], cAMP analogs [40], and methyl-β-cyclodextrin [41]) or SERPINE2 inhibitor need to be added in buck sperm cryoprotectants for AI improvement. Reactive oxygen species (ROS) are byproducts of respiration using oxygen [42]. In the pool of DNA precursor, the guanine-containing nucleotides are converted into the oxidized forms of nucleotides by the action of ROS, such as 8-oxo-dGTP, which can be incorporated into DNA incorrectly [43].…”

Section: Major Spermatozoa Proteins In Bucksmentioning

confidence: 99%

Proteomic characterization and comparison of ram (Ovis aries) and buck (Capra hircus) spermatozoa proteome using a data independent acquisition mass spectometry (DIA-MS) approach

et al. 2020

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Fresh semen is most commonly used in an artificial insemination of small ruminants, because of low fertility rates of frozen sperm. Generally, when developing and applying assisted reproductive technologies, sheep and goats are classified as one species. In order to optimize sperm cryopreservation protocols in sheep and goat, differences in sperm proteomes between ram and buck are necessary to investigate, which may contribute to differences in function and fertility of spermatozoa. In the current work, a data-independent acquisition-mass spectrometry proteomic approach was used to characterize and make a comparison of ram (Ovis aries) and buck (Capra hircus) sperm proteomes. A total of 2,109 proteins were identified in ram and buck spermatozoa, with 238 differentially abundant proteins. Proteins identified in ram and buck spermatozoa are mainly involved in metabolic pathways for generation of energy and diminishing oxidative stress. Specifically, there are greater abundance of spermatozoa proteins related to the immune protective and capacity activities in ram, while protein that inhibit sperm capacitation shows greater abundance in buck. Our results not only provide novel insights into the characteristics and potential activities of spermatozoa proteins, but also expand the potential direction for sperm cryopreservation in ram and buck.

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“…Presumably the intermembrane space ROS have easier access to cytosol through voltage dependent anion-selective channel (VDAC), as compared to matrix ROS, in which they have to cross the outer membrane and IMM (Sena and Chandel, 2012 Production of mitochondrial superoxide is estimated to be 5 to 10-fold higher than that of cytosol and nucleus . In the mitochondria matrix, superoxide is further transformed into a relatively stable H 2 O 2 by manganese (Mn)-SOD (Starkov and Wallace, 2006). In the intermembrane space, the conversion of O .…”

Section: Sources Of Cellular Rosmentioning

confidence: 99%

Characterisation of bilirubin metabolic pathway in hepatic mitochondria

Muhsain¹

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Bilirubin (BR), a toxic waste product of degraded haem, is a potent antioxidant at physiological concentrations. To achieve the maximum benefit of BR, its intracellular level needs to be carefully regulated. A system comprising of two enzymes, haem oxygenase-1 (HMOX1) and cytochrome P450 2A5 (CYP2A5) exists in the endoplasmic reticulum (ER), responsible for regulating BR homeostasis. This system is induced in response to oxidative stress. In this thesis, oxidative stress caused accumulation of these enzymes in mitochondria -major producers and targets of reactive oxygen species (ROS) -is demonstrated. To understand the significance of this intracellular targeting, properties of microsomal and mitochondrial BR metabolising enzymes were compared and the capacity of mitochondrial CYP2A5 to oxidise BR in response to oxidative stress is reported.Microsomes and mitochondrial fractions were isolated from liver homogenates of DBA/2J mice, administered with sub-toxic dose of pyrazole, an oxidant stressor. The purity of extracted organelles was determined by analysing the expressions and activities of their respective marker enzymes. HMOX1 and CYP2A5 were significantly increased in microsomes and even more so in mitochondria in response to pyrazole-induced oxidative stress. By contrast, the treatment did not increase either microsomes or mitochondrial Uridine-diphosphate-glucuronosyltransferase 1A1 (UGT1A1), the sole enzyme that catalyses BR elimination through glucuronidation.In response to pyrazole-induced oxidative stress, BR oxidation was enhanced not only in microsomes but also in mitochondria. The reaction in both control and pyrazole treated microsomes were blocked by up to 70% with anti-CYP2A5 antibody. By contrast, no CYP2A5 antibody inhibition on BR oxidation was observed in control mitochondria but was 55% inhibited in treated mitochondria. Antibody against adrenodoxin reductase (AdxR) (a component of mitochondrial monooxygenase system) had no effect on the microsomal BR oxidation, but the reaction was inhibited by up to 50% in mitochondria ii after pyrazole treatment. As in microsomes, the antibody had no effect in control mitochondria.Inhibition study with ascorbic acid -a scavenger of ROS -was undertaken to determine the contribution of ROS to BR oxidation. In control microsomes, a slight inhibition of 5% in BR degradation was noted which was augmented to 22% after pyrazole treatment. The inhibition was 100% in control mitochondria but limited to 50% after pyrazole treatment.Mass spectrometry analysis reveals that in microsomes, biliverdin (BV), the main metabolite of CYP2A5-dependant BR oxidation was formed. Meanwhile, mitochondria produced predominantly dipyrroles, the products of BR scavenging ROS. Pyrazole treatment caused mitochondria to yield relatively similar amount of BV and dipyrroles.Enzyme kinetic analysis showed that mitochondrial and microsomal CYP2A5 have an equally strong affinity towards BR. Additionally, no initiation of apoptosis, as indicated by the absence of cytosolic cytochrome...

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Yin and Yang of Mitochondrial ROS

Cited by 4 publications

References 166 publications

Zinc oxide nanoparticles induced gene mutation at the HGPRT locus and cell cycle arrest associated with apoptosis in V‐79 cells

Zinc oxide nanoparticles induced gene mutation at the HGPRT locus and cell cycle arrest associated with apoptosis in V‐79 cells

Proteomic characterization and comparison of ram (Ovis aries) and buck (Capra hircus) spermatozoa proteome using a data independent acquisition mass spectometry (DIA-MS) approach

Characterisation of bilirubin metabolic pathway in hepatic mitochondria

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