Hydrogen peroxide as a central redox signaling molecule in physiological oxidative stress: Oxidative eustress

Sies, Helmut

doi:10.1016/j.redox.2016.12.035

Cited by 1,481 publications

(1,176 citation statements)

References 119 publications

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“…A conversion from 1 O 2 to superoxide was also reported due to thermal endoperoxide activation and subsequent 1 O 2 reaction with N,N-dimethylaniline [64]. These are proof that 1 O 2 can be efficiently converted to other ROS, currently accepted as signaling molecules in cell biology [3], [5], [18], [20]. Closing the circle, superoxide can promote the production of 1 O 2 under the right conditions, like reacting with glutathione (GSH), the principal redox potential managing compound in cells [65].…”

Section: Redox Biology Of 1o2mentioning

confidence: 72%

“…This signaling role has only recently started to be acknowledged by the scientific community, in what is becoming a new branch of biology known as Redox Biology [3], [4], [5]. Within this field, the deleterious effects of ROS, whenever they are produced in too large quantities or at inappropriate times/places in living organisms, are also explored to provide answers to many disorders and diseases that have their origin in a redox deregulation of cell physiology.…”

Section: Introductionmentioning

confidence: 99%

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Direct 1O2 optical excitation: A tool for redox biology

Blázquez‐Castro

2017

Redox Biology

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Molecular oxygen (O2) displays very interesting properties. Its first excited state, commonly known as singlet oxygen (1O2), is one of the so-called Reactive Oxygen Species (ROS). It has been implicated in many redox processes in biological systems. For many decades its role has been that of a deleterious chemical species, although very positive clinical applications in the Photodynamic Therapy of cancer (PDT) have been reported. More recently, many ROS, and also 1O2, are in the spotlight because of their role in physiological signaling, like cell proliferation or tissue regeneration. However, there are methodological shortcomings to properly assess the role of 1O2 in redox biology with classical generation procedures. In this review the direct optical excitation of O2 to produce 1O2 will be introduced, in order to present its main advantages and drawbacks for biological studies. This photonic approach can provide with many interesting possibilities to understand and put to use ROS in redox signaling and in the biomedical field.

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Section: Redox Biology Of 1o2mentioning

confidence: 72%

Section: Introductionmentioning

confidence: 99%

Direct 1O2 optical excitation: A tool for redox biology

Blázquez‐Castro

2017

Redox Biology

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“…Yet the stable ROS H 2 O 2 has also been identified as an important second messenger for many physiologic processes, a role termed “oxidative eustress” (6), and has been clearly implicated in insulin signaling in fat and liver (9). A causal relationship between H 2 O 2 and metabolic responses to insulin has been described in publications dating back to the 1970s (10–12), yet many of the essential molecular details have remained unexplored.…”

Section: Introductionmentioning

confidence: 99%

Insulin-dependent metabolic and inotropic responses in the heart are modulated by hydrogen peroxide from NADPH-oxidase isoforms NOX2 and NOX4

Steinhorn

Sartoretto

Sorrentino

et al. 2017

Free Radical Biology and Medicine

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Rationale Hydrogen peroxide (H2O2) is a stable reactive oxygen species (ROS) that has long been implicated in insulin signal transduction in adipocytes. However, H2O2’s role in mediating insulin’s effects on the heart are unknown. Objective We investigated the role of H2O2 in activating insulin-dependent changes in cardiac myocyte metabolic and inotropic pathways. The sources of insulin-dependent H2O2 generation were also studied. Methods and results In addition to the canonical role of insulin in modulating cardiac metabolic pathways, we found that insulin also inhibited beta adrenergic-induced increases in cardiac contractility. Catalase and NADPH oxidase (NOX) inhibitors blunted activation of insulin-responsive kinases Akt and mTOR and attenuated beta adrenergic receptor-mediated responses. These insulin responses were lost in a mouse model of type 2 diabetes, suggesting a role for these H2O2-dependent pathways in the diabetic heart. The H2O2-sensitive fluorescent biosensor HyPer revealed rapid increases in cytosolic and caveolar H2O2 concentrations in response to insulin treatment, which were blocked by NOX inhibitors and attenuated in NOX2 KO and NOX4 KO mice. In NOX2 KO cardiac myocytes, insulin-mediated phosphorylation of Akt and mTOR was blocked, while these responses were unaffected in cardiac myocytes from NOX4 KO mice. In contrast, insulin’s effects on contractility were lost in cardiac myocytes from NOX4 KO animals but were retained in NOX2 KO mice. Conclusions These studies identify a proximal point of bifurcation in cardiac insulin signaling through the simultaneous activation of both NOX2 and NOX4. Each NOX isoform generates H2O2 in cardiac myocytes with distinct time courses, with H2O2 derived from NOX2 augmenting Akt-dependent metabolic effects of insulin, while H2O2 from NOX4 blocks beta adrenergic increases in inotropy. These findings suggest that insulin resistance in the diabetic heart may lead to potentially deleterious potentiation of beta adrenergic responses.

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“…EcSOD scavenges O 2 •− through the catalyzed dismutation of two molecules of O 2 •− to bimolecular oxygen and H 2 O 2 , which is subsequently reduced to water by catalase, peroxiredoxins and other enzymes [65]. EcSOD requires a redox-active Cu 1+/2+ ion at its active site.…”

Section: Molecular Characteristics: Ecsodmentioning

confidence: 99%

Extracellular superoxide dismutase and its role in cancer

Griess

Tom

Domann

et al. 2017

Free Radical Biology and Medicine

137

124

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Reactive oxygen species (ROS) are increasingly recognized as critical determinants of cellular signaling and a strict balance of ROS levels must be maintained to ensure proper cellular function and survival. Notably, ROS is increased in cancer cells. The superoxide dismutase family plays an essential physiological role in mitigating deleterious effects of ROS. Due to the compartmentalization of ROS signaling, EcSOD, the only superoxide dismutase in the extracellular space, has unique characteristics and functions in cellular signal transduction. In comparison to the other two intracellular SODs, EcSOD is a relatively new comer in terms of its tumor suppressive role in cancer and the mechanisms involved are less well understood. Nevertheless, the degree of differential expression of this extracellular antioxidant in cancer versus normal cells/tissues is more pronounced and prevalent than the other SODs. A significant association of low EcSOD expression with reduced cancer patient survival further suggests that loss of extracellular redox regulation promotes a conducive microenvironment that favors cancer progression. The vast array of mechanisms reported in mediating deregulation of EcSOD expression, function, and cellular distribution also supports that loss of this extracellular antioxidant provides a selective advantage to cancer cells. Moreover, overexpression of EcSOD inhibits tumor growth and metastasis, indicating a role as a tumor suppressor. This review focuses on the current understanding of the mechanisms of deregulation and tumor suppressive function of EcSOD in cancer.

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Hydrogen peroxide as a central redox signaling molecule in physiological oxidative stress: Oxidative eustress

Cited by 1,481 publications

References 119 publications

Direct 1O2 optical excitation: A tool for redox biology

Direct 1O2 optical excitation: A tool for redox biology

Insulin-dependent metabolic and inotropic responses in the heart are modulated by hydrogen peroxide from NADPH-oxidase isoforms NOX2 and NOX4

Extracellular superoxide dismutase and its role in cancer

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