Hypoxia and Reactive Oxygen Species as Modulators of Endoplasmic Reticulum and Golgi Homeostasis

Mennerich, Daniela; Kellokumpu, Sakari; Kietzmann, Thomas

doi:10.1089/ars.2018.7523

Cited by 38 publications

(19 citation statements)

References 226 publications

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“…However, after 24 h, ROS production decreased in the infected cells, and this pattern was maintained at 48 and 72 hpi ( Figure 7A). These data could be explained by the downregulation of ero1 in the late stages of infection, as the product of this gene is the largest producer of H 2 O 2 in the ER [30]. When we analysed the modulation of ROS production in vivo at 1 and 5 dpi, we found that ROS production in head kidney cells decreased with the time of infection, showing significant inhibition at 5 dpi compared to the uninfected fish ( Figure 7B).…”

Section: Ros Production Modulation During Nodavirus Infectionmentioning

confidence: 87%

RNA-Seq analysis of European sea bass (Dicentrarchus labrax L.) infected with nodavirus reveals powerful modulation of the stress response

Lama

Pereiro

Valenzuela-Muñoz

et al. 2020

Vet Res

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Nodavirus, or nervous necrosis virus (NNV), is the causative agent of viral encephalopathy and retinopathy (VER), a severe disease affecting numerous fish species worldwide. European sea bass, a cultured species of great economic importance, is highly susceptible to the disease. To better understand the response of this organism to NNV, we conducted RNA-Seq analysis of the brain and head kidney from experimentally infected and uninfected sea bass juveniles at 24 and 72 hours post-infection (hpi). Contrary to what was expected, we observed modest modulation of immune-related genes in the brain, the target organ of this virus, and some of these genes were even downregulated. However, genes involved in the stress response showed extremely high modulation. Accordingly, the genes encoding the enzymes implicated in the synthesis of cortisol were almost the only overexpressed genes in the head kidney at 24 hpi. This stress response was attenuated after 72 h in both tissues, and a progressive immune response against the virus was mounted. Moreover, experiments were conducted to determine how stress activation could impact NNV replication. Our results show the complex interplay between viral activity, the stress reaction and the immune response.

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Section: Ros Production Modulation During Nodavirus Infectionmentioning

confidence: 87%

RNA-Seq analysis of European sea bass (Dicentrarchus labrax L.) infected with nodavirus reveals powerful modulation of the stress response

Lama

Pereiro

Valenzuela-Muñoz

et al. 2020

Vet Res

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“…Emerging evidence suggests that the Golgi apparatus (GA) can directly or indirectly affect intracellular Ca 2+ fluxes, ROS, metabolism, intra-organelle pH, protein and membrane trafficking and thereby contribute to cell migration/invasion [[21], [22], [23], [24], [25]]. Although these roles have been ascribed to the GA, the intricate molecular mechanisms involved in the control of such processes are still mostly unidentified.…”

Section: Introductionmentioning

confidence: 99%

Stimulation of cell invasion by the Golgi Ion Channel GAAP/TMBIM4 via an H2O2-Dependent Mechanism

et al. 2020

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The mechanisms by which the Golgi apparatus (GA) impacts on cell invasion are poorly understood. The human Golgi Anti-Apoptotic Protein (hGAAP, also known as TMBIM4) is a highly conserved Golgi cation channel that modulates intracellular Ca2+ fluxes. Human GAAP is expressed in all human tissues, is essential for cell viability and provides resistance against a range of apoptotic stresses. Furthermore, hGAAP enhances adhesion and cell migration by increasing the turnover of focal adhesions due to activation of store-operated Ca2+ entry.Here, we describe a GA-derived mechanism that controls cell invasion. The overexpression of hGAAP stimulates 3-dimensional proteolytic cell invasion by a mechanism that is dependent on the accumulation of intracellular hydrogen peroxide, which might be produced by the hGAAP-dependent stimulation of mitochondrial respiration.These findings provide new insight into the complex mechanisms by which Ca2+ and reactive oxygen species signaling contribute to cell invasion and to the role of the GA in these processes.

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“…However, RyR2 is the most valuable player [7–9]. The hypoxic increase in [Ca 2+ ] i in PASMCs has been thought to be attributed to the enhanced production of intracellular reactive oxygen species (ROS) due to their specific effects on ion channels [10–13]. Mitochondria-derived ROS levels are regulated by intracellular Ca 2+ levels.…”

Section: Introductionmentioning

confidence: 99%

Endoplasmic reticulum Ca2+ release causes Rieske iron–sulfur protein-mediated mitochondrial ROS generation in pulmonary artery smooth muscle cells

et al. 2019

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Mitochondrial reactive oxygen species (ROS) cause Ca2+ release from the endoplasmic reticulum (ER) via ryanodine receptors (RyRs) in pulmonary artery smooth muscle cells (PASMCs), playing an essential role in hypoxic pulmonary vasoconstriction (HPV). Here we tested a novel hypothesis that hypoxia-induced RyR-mediated Ca2+ release may, in turn, promote mitochondrial ROS generation contributing to hypoxic cellular responses in PASMCs. Our data reveal that application of caffeine to elevate intracellular Ca2+ concentration ([Ca2+]i) by activating RyRs results in a significant increase in ROS production in cytosol and mitochondria of PASMCs. Norepinephrine to increase [Ca2+]i due to the opening of inositol 1,4,5-triphosphate receptors (IP3Rs) produces similar effects. Exogenous Ca2+ significantly increases mitochondrial-derived ROS generation as well. Ru360 also inhibits the hypoxic ROS production. The RyR antagonist tetracaine or RyR2 gene knockout (KO) suppresses hypoxia-induced responses as well. Inhibition of mitochondrial Ca2+ uptake with Ru360 eliminates N- and Ca2+-induced responses. RISP KD abolishes the hypoxia-induced ROS production in mitochondria of PASMCs. Rieske iron–sulfur protein (RISP) gene knockdown (KD) blocks caffeine- or NE-induced ROS production. Taken together, these findings have further demonstrated that ER Ca2+ release causes mitochondrial Ca2+ uptake and RISP-mediated ROS production; this novel local ER/mitochondrion communication-elicited, Ca2+-mediated, RISP-dependent ROS production may play a significant role in hypoxic cellular responses in PASMCs.

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Hypoxia and Reactive Oxygen Species as Modulators of Endoplasmic Reticulum and Golgi Homeostasis

Cited by 38 publications

References 226 publications

RNA-Seq analysis of European sea bass (Dicentrarchus labrax L.) infected with nodavirus reveals powerful modulation of the stress response

RNA-Seq analysis of European sea bass (Dicentrarchus labrax L.) infected with nodavirus reveals powerful modulation of the stress response

Stimulation of cell invasion by the Golgi Ion Channel GAAP/TMBIM4 via an H2O2-Dependent Mechanism

Endoplasmic reticulum Ca2+ release causes Rieske iron–sulfur protein-mediated mitochondrial ROS generation in pulmonary artery smooth muscle cells

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