Redox Regulation of Cell Survival

Trachootham, Dunyaporn; Lu, Weiqin; Ogasawara, Marcia A.; Valle, Nilsa Rivera Del; Huang, Peng

doi:10.1089/ars.2007.1957

Cited by 1,546 publications

(1,252 citation statements)

References 343 publications

(371 reference statements)

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“…The ability of increased ROS to modulate different aspects of cell function has been widely recognized (11,26,37,38,40). Our group has contributed to the knowledge of this regulation by demonstrating that H 2 O 2 induces mesangial cell contraction (6), stimulates cell proliferation (8) To decreased intracellular ROS concentration, CAT was added to the extracellular media of the cells.…”

Section: Discussionmentioning

confidence: 99%

“…ROS are derived from several compartments inside the cells: mitochondria, peroxisomes, plasma membrane, endoplasmic reticulum, Golgi complex, lysosomes and the nucleus, where there are enzyme systems that synthesize ROS (7,26,37). Although this synthesis is usually considered as a whole, probably the different enzymes are responsible for ROS production for specific cellular functions.…”

Section: Discussionmentioning

confidence: 99%

“…The balance between production and elimination is tightly regulated and ensures the proper maintenance of cellular metabolism and homeostasis. In general, moderate levels of ROS are involved in biological processes such as cell proliferation, differentiation and survival (11,37). Exogenous stimuli may also modulate ROS balance and in these cases transient ROS production can act as an intracellular signalling mechanism, regulating a broad variety of genes and cell functions (2,31,39).…”

Section: Introductionmentioning

confidence: 99%

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Intracellular redox equilibrium is essential for the constitutive expression of AP-1 dependent genes in resting cells: Studies on TGF-β1 regulation

González-Ramos

Mora

Garcı́a

et al. 2012

The International Journal of Biochemistry & Cell Biology

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Intracellular redox equilibrium is essential for the constitutive expression of AP-1 dependent genes in resting cells: Studies on TGF-β1 regulation

González-Ramos

Mora

Garcı́a

et al. 2012

The International Journal of Biochemistry & Cell Biology

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“…ROS as messengers have been associated to signaling by insulin, cytokines and many growth factors [35,36], whose activity regulates classic signaling cascades such as the extracellular ERK, JNK, and MAPK cascades, as well as the PI3-K/Akt, PLC-γ1 and JAK/STAT pathways [37,38]. These pathways in turn exert their phenotypic effects largely by modulating the activities of central transcription factors, among them NF-kB, AP-1, Nrf2, FoxOs, HIF-1α and p53 [39,40]. Furthermore, the activities of enzymes such as catalase, GPxs and Prdx have been shown to be regulated by kinases and phosphatases that are susceptible to oxidative modifications, thus creating a regulatory network [9,10].…”

Section: The Role Of Ros In Signal Transductionmentioning

confidence: 99%

Taking a “good” look at free radicals in the aging process

Hekimi

Lapointe

Yang

2011

Trends in Cell Biology

521

373

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The mitochondrial free radical theory of aging (MFRTA) proposes that aging is caused by damage to macromolecules from mitochondrial reactive oxygen species (ROS). This is based on the observed association of the rate of aging and the aged phenotype with the generation of ROS and with oxidative damage. The theory has led to the strong conviction in the general public that the consumption of antioxidants is crucial to health and beneficial to lifespan. However, a variety of recent findings convincingly demonstrate that ROS generation and oxidative damage cannot be the cause of aging. Here we propose that ROS play a role in mediating a stress response to agedependent damage, which could generate the observed correlation between aging and ROS without implying that ROS cause aging. Redefining our understanding of the relationship between ROS and agingMitochondria are a major source of reactive oxygen species (ROS), a type of molecule that includes free radicals such as superoxide. ROS spontaneously oxidize and damage macromolecules such as proteins, lipids and nucleic acids. Cells and organisms are said to be sustaining oxidative stress when an imbalance between ROS generation and detoxification or repair leads to an increase in the level of ROS-dependent damage. The mitochondrial free radical theory of aging (MFRTA) has provided an attractive framework that integrates numerous observations about the generation, the toxicity and the detoxification of ROS, as well as about how these parameters change with the physiological state of cells and organisms and with chronological age. The theory proposes that aging is actually caused by the toxicity of ROS through a vicious cycle in which ROS damage to the constituents of mitochondria leads to the generation of more ROS. The theory is based on numerous observations, including (1) that there is a strong correlation between chronological age and the level of ROS generation and oxidative damage, (2) that mitochondrial function is gradually lost during aging, (3) that inhibition of mitochondrial function can enhance ROS production, and (4) that several age-dependent diseases are associated with severe increases in oxidative stress.The strength of the MFRTA is that it provides a framework for many observations while also stating a plausible causal theory of aging. Furthermore, it provided a clear research program by proposing a theory to be tested as well as by suggesting that decreasing the generation of ROS will result in health benefits. In fact the MFRTA is often taught in textbooks and in *

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“…In fact, cytokines, including IFN-ɣ, induce ROS production through NADPH oxidase (NOX) (Lambeth 2004) which may lead to several modifications of intracellular signaling pathways, by affecting the activities of kinases and phosphatases (Trachootham et al 2008;Sundaresan et al 1995). ROS generation is mostly derived from the metabolism of oxygen (Halliwell 1999), whose harmful effects result from its metabolic reduction to highly reactive and toxic molecules (Buechter 1988).…”

Section: Introductionmentioning

confidence: 99%

ROS mediates interferon gamma induced phosphorylation of Src, through the Raf/ERK pathway, in MCF-7 human breast cancer cell line

Zibara

Zeidan

Bjeije

et al. 2016

J. Cell Commun. Signal.

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Interferon gamma (IFN-ɣ) is a pleiotropic cytokine which plays dual contrasting roles in cancer. Although IFN-ɣ has been clinically used to treat various malignancies, it was recently shown to have protumorigenic activities. Reactive oxygen species (ROS) are overproduced in cancer cells, mainly due to NADPH oxidase activity, which results into several changes in signaling pathways. In this study, we examined IFN-ɣ effect on the phosphorylation levels of key signaling proteins, through ROS production, in the human breast cancer cell line MCF-7. After treatment by IFN-ɣ, results showed a significant increase in the phosphorylation of STAT1, Src, raf, AKT, ERK1/2 and p38 signaling molecules, in a time specific manner. Src and Raf were found to be involved in early stages of IFN-ɣ signaling since their phosphorylation increased very rapidly. Selective inhibition of Src-family kinases resulted in an immediate significant decrease in the phosphorylation status of Raf and ERK1/2, but not p38 and AKT. On the other hand, IFN-ɣ resulted in ROS generation, through H 2 O 2 production, whereas pre-treatment with the ROS inhibitor NAC caused ROS inhibition and a significant decrease in the phosphorylation levels of AKT, ERK1/2, p38 and STAT1. Moreover, pretreatment with a selective NOX1 inhibitor resulted in a significant decrease of AKT phosphorylation.Finally, no direct relationship was found between ROS production and calcium mobilization. In summary, IFN-ɣ signaling in MCF-7 cell line is ROS-dependent and follows the Src/ Raf/ERK pathway whereas its signaling through the AKT pathway is highly dependent on NOX1.

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Redox Regulation of Cell Survival

Cited by 1,546 publications

References 343 publications

Intracellular redox equilibrium is essential for the constitutive expression of AP-1 dependent genes in resting cells: Studies on TGF-β1 regulation

Intracellular redox equilibrium is essential for the constitutive expression of AP-1 dependent genes in resting cells: Studies on TGF-β1 regulation

Taking a “good” look at free radicals in the aging process

ROS mediates interferon gamma induced phosphorylation of Src, through the Raf/ERK pathway, in MCF-7 human breast cancer cell line

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