Reactive Oxygen Species in the Activation of MAP Kinases

Son, Young‐Ik; Kim, Sang-Duck; Chung, Hun‐Taeg; Pae, Hyun‐Ock

doi:10.1016/b978-0-12-405881-1.00002-1

Cited by 376 publications

(276 citation statements)

References 55 publications

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“…Moreover, in the liver the imbalance of oxidant/antioxidant system can also lead to the activation of stress-sensitive signaling pathways called MAPK [34, 35]. It is also worth of note that in human hepatocarcinoma cell lines cells multiple membrane-starting pathways have been reported to be rapidly activated by the ER-estradiol complex and the blockade of phospholipase C/protein kinase C, ERK, and AKT pathways completely prevented the estradiol-induced DNA synthesis.…”

Section: Discussionmentioning

confidence: 99%

Modulation of Oxidative Stress by 17 β-Estradiol and Genistein in Human Hepatic Cell Lines In Vitro

Surico¹,

Ercoli²,

Farruggio

et al. 2017

Cell Physiol Biochem

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Background/Aims: estrogens and phytoestrogens exert hepatoprotection through mechanisms not clearly examined yet. Here, we investigated the protective effects exerted by 17β-estradiol and genistein against oxidative stress in hepatocytes and hepatic stellate cells (HSCs) and the involvement of specific receptors and the intracellular signalling. Methods: Huh7.5 and LX-2, alone or in co-culture with Huh7.5, were treated with 17β-estradiol and genistein alone or in the presence of menadione and of estrogen receptors (ERs) and G protein-coupled-estrogenic-receptors (GPER) blockers. Cell viability, mitochondrial membrane potential and oxidant/antioxidant system were measured by specific kits. Western Blot was used for the analysis of Akt and p38-mitogen-activated-protein kinases (MAPK) activation and α-smooth-muscle actin expression. Results: In Huh7.5, 17β-estradiol and genistein prevented the effects of peroxidation by modulating Akt and p38MAPK activation. Similar antioxidant and protective findings were obtained in LX-2 of co-culture experiments, only. ERs and GPER blockers were able to prevent the effects of 17β-estradiol and genistein. Conclusion: In Huh7.5 and LX-2, 17β-estradiol and genistein counteract the effects of peroxidation through the involvement of ERs and GPER and by an intracellular signalling related to Akt and p38MAPK. As concerning LX-2, paracrine factors released by Huh7.5 play a key role in protection against oxidative stress.

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Section: Discussionmentioning

confidence: 99%

Modulation of Oxidative Stress by 17 β-Estradiol and Genistein in Human Hepatic Cell Lines In Vitro

Surico¹,

Ercoli²,

Farruggio

et al. 2017

Cell Physiol Biochem

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“…The MAPKs are involved in the regulation of several cellular activities such as proliferation, differentiation, inflammatory responses, and apoptosis. ROS can activate MAPKs by the oxidative modification of signaling proteins or intracellular kinases such as MAPK3s (56).…”

Section: Discussionmentioning

confidence: 99%

Antioxidant Defenses of Francisella tularensis Modulate Macrophage Function and Production of Proinflammatory Cytokines

Rabadi

Sanchez

Varanat

et al. 2016

Journal of Biological Chemistry

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Francisella tularensis, the causative agent of a fatal human disease known as tularemia, has been used in the bioweapon programs of several countries in the past, and now it is considered a potential bioterror agent. Extreme infectivity and virulence of F. tularensis is due to its ability to evade immune detection and to suppress the host's innate immune responses. However, Francisella-encoded factors and mechanisms responsible for causing immune suppression are not completely understood. Macrophages and neutrophils generate reactive oxygen species (ROS)/reactive nitrogen species as a defense mechanism for the clearance of phagocytosed microorganisms. ROS serve a dual role; at high concentrations they act as microbicidal effector molecules that destroy intracellular pathogens, and at low concentrations they serve as secondary signaling messengers that regulate the expression of various inflammatory mediators. We hypothesized that the antioxidant defenses of F. tularensis maintain redox homeostasis in infected macrophages to prevent activation of redox-sensitive signaling components that ultimately result in suppression of pro-inflammatory cytokine production and macrophage microbicidal activity. We demonstrate that antioxidant enzymes of F. tularensis prevent the activation of redox-sensitive MAPK signaling components, NF-B signaling, and the production of pro-inflammatory cytokines by inhibiting the accumulation of ROS in infected macrophages. We also report that F. tularensis inhibits ROS-dependent autophagy to promote its intramacrophage survival. Collectively, this study reveals novel pathogenic mechanisms adopted by F. tularensis to modulate macrophage innate immune functions to create an environment permissive for its intracellular survival and growth.Francisella tularensis is a Gram-negative intracellular pathogen and the causative agent of a fatal human disease known as tularemia. F. tularensis is classified into four subspecies as follows: F. tularensis subspecies tularensis; F. tularensis subspecies holarctica; F. tularensis subspecies mediasiatica, and F. tularensis subspecies novicida. All classifications are based on virulence, genetics, and metabolic characteristics. F. tularensis subspecies tularensis (type A) is the most virulent of all four Francisella subspecies. About 70% of tularemia cases in North America are a result of type A Francisella with an infectivity dose of less than 10 colony-forming units (cfu) in humans (1). The live vaccine strain (LVS) 3 is a derivative of Russian S15 strain of F. tularensis subspecies holarctica (type B). F. tularensis LVS is not approved for mass vaccinations in the United States due to adverse reactions in vaccinated individuals (2). F. tularensis LVS is relatively avirulent in humans and therefore commonly used as a surrogate for the more virulent SchuS4 strain to study tularemia pathogenesis. F. tularensis subspecies mediasiatica and novicida are rarely associated with human tularemia and have been isolated in Asia and in North America and Australia, re...

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“…In particular, ROS have been reported to activate the JNK pathway (Son et al, 2013). Interestingly, Debcl is localized in mitochondria, which are known to be the major site of ROS production in cells.…”

Section: Debcl Is Required Downstream Of Buffy For Rbf1-induced Apoptmentioning

confidence: 99%

The Drosophila retinoblastoma protein, Rbf1, induces a debcl and drp1-dependent mitochondrial apoptosis.

Clavier

Ruby

Rincheval-Arnold

et al. 2015

Journal of Cell Science

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In accordance with its tumor suppressor role, the retinoblastoma protein pRb can ensure pro-apoptotic functions. Rbf1, the Drosophila homolog of Rb, also displays a pro-apoptotic activity in proliferative cells. We have previously shown that the Rbf1 pro-apoptotic activity depends on its ability to decrease the level of anti-apoptotic proteins such as the Bcl-2 family protein Buffy. Buffy often acts in an opposite manner to Debcl, the other Drosophila Bcl-2-family protein. Both proteins can localize at the mitochondrion, but the way they control apoptosis still remains unclear. Here, we demonstrate that Debcl and the pro-fission gene Drp1 are necessary downstream of Buffy to trigger a mitochondrial fragmentation during Rbf1-induced apoptosis. Interestingly, Rbf1-induced apoptosis leads to a Debcl-and Drp1-dependent reactive oxygen species production, which in turn activates the Jun Kinase pathway to trigger cell death. Moreover, we show that Debcl and Drp1 can interact and that Buffy inhibits this interaction. Notably, Debcl modulates Drp1 mitochondrial localization during apoptosis. These results provide a mechanism by which Drosophila Bcl-2 family proteins can control apoptosis, and shed light on a link between Rbf1 and mitochondrial dynamics in vivo.

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Reactive Oxygen Species in the Activation of MAP Kinases

Cited by 376 publications

References 55 publications

Modulation of Oxidative Stress by 17 β-Estradiol and Genistein in Human Hepatic Cell Lines In Vitro

Modulation of Oxidative Stress by 17 β-Estradiol and Genistein in Human Hepatic Cell Lines In Vitro

Antioxidant Defenses of Francisella tularensis Modulate Macrophage Function and Production of Proinflammatory Cytokines

The Drosophila retinoblastoma protein, Rbf1, induces a debcl and drp1-dependent mitochondrial apoptosis.

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