Hypoxia decreases ROS level in human fibroblasts

Sgarbi, Gianluca; Gorini, Giulia; Costanzini, Anna; Barbato, Simona; Baracca, Alessandra

doi:10.1016/j.biocel.2017.05.005

Cited by 33 publications

(24 citation statements)

References 62 publications

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“…[59] that may contribute to the oxidized protein build-up observed in the absence of Lon ( Fig 1A and B). In contrast, together with the elongated mitochondrial network, the absence of increased protein carbonylation noted in Lon-depleted cells grown under 3% O2 ( Fig 1C) confirm that cells adapt here to hypoxia using a different strategy, probably by decreasing ROS levels as previously reported in human fibroblasts [60].…”

Section: Discussionsupporting

confidence: 86%

Mitochondrial Lon protease - depleted HeLa cells exhibit proteome modifications related to protein quality control, stress response and energy metabolism

Hamon

Gergondey

L’honoré

et al. 2020

Free Radical Biology and Medicine

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Lon protease knockdown promotes oxidative stress and protein oxidation in HeLa cells  Lon protease deficiency affects mitochondrial network morphology and cell proliferation  Lon depletion impacts on stress response and energy metabolism protein expression  Lon protease depletion decreases cell energy metabolic activity and ATP production Mitochondrial Lon protease-depleted HeLa cells exhibit proteome modifications related to protein quality control, stress response and energy metabolism

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Section: Discussionsupporting

confidence: 86%

Mitochondrial Lon protease - depleted HeLa cells exhibit proteome modifications related to protein quality control, stress response and energy metabolism

Hamon

Gergondey

L’honoré

et al. 2020

Free Radical Biology and Medicine

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“…Hypoxia is known to involve altered ROS signaling and, though often controversially discussed [38, 39], it is meanwhile accepted that redox response to hypoxia can be cell-type and even cell compartment specific [40, 41] and that mitochondria are a source of ROS which is released to the cytosol in a controlled process [42, 43]. We therefore measured cytosolic as well as mitochondrial hydrogen peroxide levels under both conditions.…”

Section: Resultsmentioning

confidence: 99%

Metabolic Plasticity Enables Circadian Adaptation to Acute Hypoxia in Zebrafish Cells

Sandbichler¹,

Jansen²,

Peer³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Reduced oxygen availability, hypoxia, is frequently encountered by organisms, tissues and cells, in aquatic environments as well as in high altitude or under pathological conditions such as infarct, stroke or cancer. The hypoxic signaling pathway was found to be mutually intertwined with circadian timekeeping in vertebrates and, as reported recently, also in mammals. However, the impact of hypoxia on intracellular metabolic oscillations is still unknown. Methods: For determination of metabolites we used Multilabel Reader based fluorescence and luminescence assays, circadian levels of Hypoxia Inducible Factor 1 alpha and oxidized peroxiredoxins were semi quantified by Western blotting and ratiometric quantification of cytosolic and mitochondrial H₂O₂ was achieved with stable transfections of a redox sensitive green fluorescent protein sensor into zebrafish fibroblasts. Circadian oscillations of core clock gene mRNA´s were assessed using realtime qPCR with subsequent cosine wave fit analysis. Results: Here we show that under normoxia primary metabolic activity of cells predominately occurs during day time and that after acute hypoxia of two hours, administrated immediately before each sampling point, steady state concentrations of glycolytic key metabolites such as glucose and lactate reveal to be highly rhythmic, following a circadian pattern with highest levels during the night periods and reflecting the circadian variation of the cellular response to hypoxia. Remarkably, rhythms in glycolysis are transferred to cellular energy states under normoxic conditions, so that ADP/ATP ratios oscillate as well, which is the first evidence for cycling ADP/ATP pools in a metazoan cell line to our knowledge. Furthermore, the hypoxia induced alterations in rhythms of glycolysis lead to the alignment of three major cellular redox systems, namely the circadian oscillations of NAD⁺/NADH and NADP⁺/NADPH ratios and of increased nocturnal levels of oxidized peroxiredoxins, resulting in a highly oxidized nocturnal cellular environment. Of note, circadian rhythms of cytosolic H₂O₂ remain unaltered, while the transcriptional clock is already attenuated, as it is known to occur also under chronic hypoxia. Conclusion: We therefor propose that the realignment of metabolic redox oscillations might initiate the observed hypoxia induced attenuation of the transcriptional clock, based on the reduced binding affinity of the CLOCK/BMAL complex to the DNA in an oxidized environment.

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“…Routine mycoplasma tests were performed to ensure the absence of contamination. All the cell types were cultured simultaneously for up to 24 h in two different incubators; in a humidified atmosphere at 37 °C containing 5% CO 2 and either atmospheric (21% O 2 ; pO 2 = 21 kPa) or low (0.5% O 2 ; pO 2 = 0.5 kPa) oxygen tension as previously reported [ 15 ].…”

Section: Methodsmentioning

confidence: 99%

“…An important feature that is still under discussion concerns the level and the potential role of Reactive Oxygen Species (ROS) in cell adaptation to hypoxia. Several studies demonstrated that under hypoxia ROS production, mostly derived from the mitochondrial electron transport chain (ETC), increased in both normal and transformed cells [ 11 , 12 , 13 , 14 ], whereas others reported the opposite [ 15 , 16 , 17 , 18 ]. Two more peculiar papers are worth being mentioned: the first reported that hypoxia causes a ROS decrease in the mitochondrial matrix compartment of vascular smooth muscle cells, whereas it increases ROS production in the mitochondrial intermembrane space, which diffuse to the cytosol [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Hypoxia and IF1 Expression Promote ROS Decrease in Cancer Cells

Sgarbi

Gorini

Liuzzi

et al. 2018

Cells

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The role of reactive oxygen species (ROS) in the metabolic reprogramming of cells adapted to hypoxia and the interplay between ROS and hypoxia in malignancy is under debate. Here, we examined how ROS levels are modulated by hypoxia in human cancer compared to untransformed cells. Short time exposure (20 min) of either fibroblasts or 143B osteosarcoma cells to low oxygen tension down to 0.5% induced a significant decrease of the cellular ROS level, as detected by the CellROX fluorescent probe (−70%). Prolonging the cells’ exposure to hypoxia for 24 h, ROS decreased further, reaching nearly 20% of the normoxic value. In this regard, due to the debated role of the endogenous inhibitor protein (IF1) of the ATP synthase complex in cancer cell bioenergetics, we investigated whether IF1 is involved in the control of ROS generation under severe hypoxic conditions. A significant ROS content decrease was observed in hypoxia in both IF1-expressing and IF1- silenced cells compared to normoxia. However, IF1-silenced cells showed higher ROS levels compared to IF1-containing cells. In addition, the MitoSOX Red-measured superoxide level of all the hypoxic cells was significantly lower compared to normoxia; however, the decrease was milder than the marked drop of ROS content. Accordingly, the difference between IF1-expressing and IF1-silenced cells was smaller but significant in both normoxia and hypoxia. In conclusion, the interplay between ROS and hypoxia and its modulation by IF1 have to be taken into account to develop therapeutic strategies against cancer.

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Hypoxia decreases ROS level in human fibroblasts

Cited by 33 publications

References 62 publications

Mitochondrial Lon protease - depleted HeLa cells exhibit proteome modifications related to protein quality control, stress response and energy metabolism

Mitochondrial Lon protease - depleted HeLa cells exhibit proteome modifications related to protein quality control, stress response and energy metabolism

Metabolic Plasticity Enables Circadian Adaptation to Acute Hypoxia in Zebrafish Cells

Hypoxia and IF1 Expression Promote ROS Decrease in Cancer Cells

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