Helmut Sies

Heinrich Heine University Düsseldorf | HHU · Institute of Biochemistry and Molecular Biology I

Oxidation-reduction (redox) reactions are central to the existence of life. Reactive species of oxygen, nitrogen and sulfur mediate redox control of a wide range of essential cellular processes. Yet, excessive levels of oxidants are associated with ageing and many diseases, including cardiological and neurodegenerative diseases, and cancer. Hence,...

Redox reactions are linked to fundamental life processes. Recent research revealed a central role of hydrogen peroxide (H2O2) in redox regulation and oxidative stress responses. A physiological low level of H2O2 is essential in redox signaling, “oxidative eustress”, whereas supraphysiological H2O2 is detrimental, causing molecular damage, “oxidativ...

Aims Endothelial function is essential for cardiovascular health, and flow-mediated dilation (FMD) is an established technique to measure it. This paper is to assess FMD values in apparently healthy individuals and provide reference values to facilitate wider clinical use. Methods and Results In 1,579 apparently healthy individuals (aged 18-76), f...

‘Reactive oxygen species’ (ROS) is a generic term that defines a wide variety of oxidant molecules with vastly different properties and biological functions that range from signalling to causing cell damage. Consequently, the description of oxidants needs to be chemically precise to translate research on their biological effects into therapeutic be...

Research on oxidants and electrophiles has shifted from focusing on damage to biomolecules to the more fine-grained physiological arena. Redox transitions as excursions from a steady-state redox set point are continually ongoing in maintenance of redox balance. Current excitement on these topics results from the fact that recent research provided m...

In the open metabolic system, redox-related signaling requires continuous monitoring and fine-tuning of the steady-state redox set point. The ongoing oxidative metabolism is a persistent challenge, denoted as oxidative eustress, which operates within a physiological range that has been called the ‘Homeodynamic Space’, the ‘Goldilocks Zone’ or the ‘...

My interest in biological chemistry proceeded from enzymology in vitro to the study of physiological chemistry in vivo Investigating biological redox reactions, I identified hydrogen peroxide (H2O2) as a normal constituent of aerobic life in eukaryotic cells. This finding led to developments that recognized the essential role of H2O2 in metabolic r...

Ebselen is an organoselenium compound exhibiting hydroperoxide- and peroxynitrite-reducing activity, acting as a glutathione peroxidase and peroxiredoxin enzyme mimetic. Ebselen reacts with a multitude of protein thiols, forming a selenosulfide bond, which results in pleiotropic effects of antiviral, antibacterial and anti-inflammatory nature. The...

‘Reactive oxygen species’ (ROS) is an umbrella term for an array of derivatives of molecular oxygen that occur as a normal attribute of aerobic life. Elevated formation of the different ROS leads to molecular damage, denoted as ‘oxidative distress’. Here we focus on ROS at physiological levels and their central role in redox signalling via differen...

In the research area of redox biology, the concept of oxidative stress encompasses redox imbalance, affecting redox signaling and leading to damage of biomolecules. Stress response systems can counteract, restoring redox balance. Normal metabolism and functions maintaining steady state require low levels of oxidants, denoted as oxidative eustress....

Light-exposed tissues are affected by photooxidative stress that causes and promotes diseases, including skin cancer and cataract and age-related macular degeneration (AMD). Nutrition supplies components for powerful enzymatic and nonenzymatic defense systems. Among the micronutrients, carotenoids and flavonoids from dietary sources have been exami...

The global concept of oxidative stress is defined as “an imbalance between oxidants and antioxidants in favor of the oxidants, leading to a disruption of redox signaling and control and/or molecular damage” (see Sies and Jones¹¹). In accordance with H. Selye’s initial concept of stress, the term oxidative stress implies an adaptive oxidative stress...

Selenium-binding protein 1 (SELENBP1) has recently been reported to catalyse the oxidation of methanethiol, an organosulfur compound produced by gut microbiota. Two of the reaction products of methanethiol oxidation, hydrogen peroxide and hydrogen sulphide, serve as signalling molecules for cell differentiation. Indeed, colonocyte differentiation h...

We designed a genetically encoded ratiometric fluorescent probe with enhanced brightness and optimized pKa, SypHer3s, which responds to pH changes in different cellular compartments. SypHer3s was successfully utilized for imaging...

Oxidative stress as a concept in redox biology and medicine has witnessed fulminant development of the past 30-odd years. It is a global concept, defined as “an imbalance between oxidants and antioxidants in favor of the oxidants, leading to a disruption of redox signaling and control and/or molecular damage” (Sies H, Jones DP: Oxidative stress. In...

Hydrogen peroxide is a stable product of water radiolysis, occurring at nanomolar concentration upon low dose ionizing radiation (<100 mGy). In view of the recent recognition of H2O2 as a central redox signaling molecule which, likewise, is maintained in the nanomolar range in cells, we propose a role for H2O2 in radiation hormesis. Low dose ionizi...

Oxidative stress is two sided: Whereas excessive oxidant challenge causes damage to biomolecules, maintenance of a physiological level of oxidant challenge, termed oxidative eustress, is essential for governing life processes through redox signaling. Recent interest has focused on the intricate ways by which redox signaling integrates these convers...

Epidemiology generates interest by providing plausible associations, and biochemistry and molecular biology attempt to pin down cause-effect relationships in concrete molecular terms. In this Viewpoint, we posit that coronary heart disease (CHD) and its relationship to work stress may qualify as prime example of an entity that profits from recent a...

Cell metabolism relies on redox reactions to harness energy for life. Cells need to sense and regulate their internal redox state, typically with cysteine thiols.

Hydrogen peroxide emerged as major redox metabolite operative in redox sensing, signaling and redox regulation. Generation, transport and capture of H2O2 in biological settings as well as their biological consequences can now be addressed. The present overview focuses on recent progress on metabolic sources and sinks of H2O2 and on the role of H2O2...

Oxidative stress is an imbalance between oxidants and antioxidants in favor of the oxidants, leading to a disruption of redox signaling and control and/or molecular damage (Sies H, Jones DP, Oxidative stress. In: Fink G (eds) Encyclopedia of stress. 2nd edn, vol 3, Elsevier, Amsterdam, pp 45–48, 2007). The concept of oxidative stress, first formula...

The first Institute of Biochemistry in Japan was founded by Leonor Michaelis from Berlin at Nagoya in 1922, and there have been numerous interrelations between Japanese and German biochemists since. Some such relationships are presented here from a personal point of view as one illustrative example, which could be extended amply by the experience o...

This Special Issue contains selected and peer-reviewed research presented at the 7th International Conference on Polyphenols and Health (ICPH) was held in Tours, France, October 25–27, 2015We thank the authors for submitting their workWe would like to express our thanks also to the authors of those manuscripts, several of which were found to be mor...

The field of oxidative stress research embraces chemistry, biochemistry, cell biology, physiology and pathophysiology, all the way to medicine and health and disease research. “Oxidative stress is an imbalance between oxidants and antioxidants in favor of the oxidants, leading to a disruption of redox signaling and control and/or molecular damage”...

Selenoenzymes and nuclear factor erythroid 2-related factor 2 (Nrf2)-regulated phase II enzymes comprise key components of the cellular redox and antioxidant systems, which show multiple interrelations. Deficiency of the micronutrient selenium (Se) and impaired biosynthesis of selenoproteins have been reported to result in induction of Nrf2 target...

The 'Redox Code' is a set of principles that defines the positioning of the nicotinamide adenine dinucleotide (NAD, NADP) and thiol/disulfide systems as well as the thiol redox proteome in space and time in biological systems. The code is richly elaborated in oxygen-dependent life, where activation/deactivation cycles involving O2 and H2O2 contribu...

Viral and bacterial infections are often associated with deficiencies in macronutrients and micronutrients, including the essential trace element selenium. In selenium deficiency, benign strains of Coxsackie and influenza viruses can mutate to highly pathogenic strains. Dietary supplementation to provide adequate or supranutritional selenium supply...

“Oxidative stress” as a concept in redox biology and medicine has been formulated in 1985; at the beginning of 2015, approx. 140,000 PubMed entries show for this term. This concept has its merits and its pitfalls. Among the merits is the notion, elicited by the combined two terms of (i) aerobic metabolism as a steady-state redox balance, and (ii) t...

Eimeriosis, a widespread infectious disease of livestock, is caused by coccidian protozoans of the genus Eimeria. These obligate intracellular parasites strike the digestive tract of their hosts and give rise to enormous economic losses, particularly in poultry, ruminants including cattle, and rabbit farming. Vaccination, though a rational prophyla...

In mammalian tissues, ultraweak chemiluminescence arising from biomolecule oxidation has been attributed to the radiative deactivation of singlet molecular oxygen [O2 ((1)Δg)] and electronically excited triplet carbonyl products involving dioxetane intermediates. Herein, we describe evidence of the generation of O2 ((1)Δg) in aqueous solution via e...

Hydrogen peroxide, the nonradical 2-electron reduction product of oxygen, is a normal aerobic metabolite occurring at about 10 nm intracellular concentration. In liver, it is produced at 50 nmol/min/g of tissue, which is about 2% of total oxygen uptake at steady state. Metabolically generated H2O2 emerged from recent research as a central hub in re...

Abstract Hydrogen peroxide acts as a signaling molecule in early adipogenesis. In differentiating adipocytes, elevated hydrogen peroxide generation is balanced through induction of antioxidant enzymes such as catalase and peroxiredoxins. Thioredoxin reductases (TrxR) and glutathione peroxidases (GPx) are selenoenzymes which constitute part of the m...

Recent observational and clinical studies have raised interest in the potential health effects of cranberry consumption, an association that appears to be due to the phytochemical content of this fruit. The profile of cranberry bioactives is distinct from that of other berry fruit, being rich in A-type proanthocyanidins (PACs) in contrast to the B-...

Here, we investigated the effect of the trace element selenium (Se) on course and outcome of Eimeria-paplllata-induced coccidiosis in mice. Male mice were fed on Se-adequate (0.15 ppm), Se-deficient, and Se-high diets (1.0 ppm) for 6 weeks. Mice were orally infected with 1,000 oocysts. The prepatent period lasts for 3 days, but the course of infect...

The micronutrient selenium and selenium-containing selenoproteins are involved in prevention of inflammation and carcinogenesis in the gut. Selenoprotein P (Sepp1), the plasma selenium transport protein, is secreted primarily from hepatocytes, but Sepp1 mRNA is also abundant in the intestine. By immunofluorescence analysis, we show that Sepp1 level...

Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one; PZ-51, DR-3305), is an organoselenium compound with glutathione peroxidase (GPx)-like, thiol-dependent, hydroperoxide reducing activity. As an enzyme mimic for activity of the selenoenzyme GPx, this compound has proved to be highly useful in research on mechanisms in redox biology. Furthermore, the...

“Oxidative Stress” denotes an imbalance between oxidants and antioxidants in favor of the oxidants, leading to a disruption of redox signaling and control and/or molecular damage. It is fascinating to note the development of the general concept of “oxidative stress” from basic chemistry of biomolecules to detailed ramifications in neurodegenerative...

The essential trace element selenium, as selenocysteine, is incorporated into antioxidant selenoproteins such as glutathione peroxidases (GPx), thioredoxin reductases (TrxR) and selenoprotein P (Sepp1). Although comparatively low in selenium content, the brain exhibits high priority for selenium supply and retention under conditions of dietary sele...

Significance: Adequate and supranutritional selenium (Se) intake, maintaining full expression of selenoproteins, has been assumed to be beneficial for human health with respect to prevention of cancer. Strikingly, the effectiveness of dietary Se supplementation depends on many factors: baseline Se status, age, gender, and genetic background of an...

Progressive loss of pancreatic beta-cell mass is a crucial feature of type 2 diabetes mellitus. As beta-cells express very low amounts of the antioxidant enzymes catalase and glutathione peroxidase (GPx), they appear to be particularly vulnerable to oxidative damage in the pathogenesis of diabetes. Here, we investigated the pancreatic expression pa...

Protection against skin damage from sunlight by nutritional means has been examined. Likewise, there has been work on the topical application of phytochemicals to the skin. This review focuses on the nutritional aspect of phytochemicals in humans-ie, the provision of carotenoid micronutrients by dietary means to the skin and their role in protectio...

No abstract available.

Criteria for assessing the purported protection by flavanol-rich foods against vascular dysfunction and oxidative damage to biomolecules was the subject of the 27th Hohenheim Consensus Conference held on July 11, 2011. State-of-the-art evidence was put into perspective, focusing on several questions that were followed by a consensus answer. Among t...

Carotenoids are micronutrients present mainly in fruits and vegetables, and they are ingested from these sources with the diet. They exhibit specific antioxidant activity but also influence signaling and gene expression at the cellular level. β-Carotene and lycopene, the colorants of carrots and tomatoes, respectively, are among the most prominent...

Supranutritional selenium (Se) intake and high serum Se levels have been associated epidemiologically with increased risk for type 2 diabetes, suggesting adverse effects of dietary Se compounds and/or antioxidant selenoenzymes on the sensitivity of target tissues for insulin. Here, we compared the capability of inorganic (sodium selenite and sodium...

Modern metabolic research in hepatology employs non-invasive techniques of the whole organism, and it includes studying the intact organ. Following recent decades of efforts in culturing isolated cells and studying their properties separately, it has become clear that the spatiotemporal organisation of different cell types in a tissue requires stud...

Glutathione peroxidase 4 (GPx4), an abundant selenoenzyme, is ubiquitously expressed in a tissue-, cell- and differentiation-dependent manner, and it is localized in cytoplasmic, mitochondrial, and nuclear cellular compartments. Here, we report cytoplasmic and nuclear localization of GPx4 in Caco-2 intestinal epithelial cells. Enterocytic different...

Accumulating evidence indicates a critical role of microRNAs (miRNAs) in the outcome of diseases. Here, we investigate the effect of garlic on the intestinal miRNA signature of male Balb/c mice during infections with Eimeria papillata. Garlic decreases the intracellular development as evidenced by a lowered fecal output of E. papillata oocysts from...

The dietary flavanol (-)-epicatechin has been suggested to mediate its vasodilatory effect by increasing nitric oxide levels in endothelial cells. To directly prove the formation of nitric oxide (NO) in human endothelial cells (HUVEC) in vitro by trapping NO to yield a fluorescent nitrosamine. HUVEC were treated with (-)-epicatechin; nitrite and NO...

The essential trace element selenium has long been considered to exhibit anti-diabetic and insulin-mimetic properties, but recent epidemiological studies indicated supranutritional selenium intake and high plasma selenium levels as possible risk factors for development of type 2 diabetes, pointing to adverse effects of selenium on carbohydrate meta...

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The green tea flavonoid epigallocatechin gallate (EGCG) is demonstrated in this study to modulate FoxO transcription factors in human skin fibroblasts in culture. EGCG at 1 microM stimulated FoxO transcription factor nuclear accumulation and DNA binding activity. This effect was masked at higher EGCG concentrations (100 microM) by EGCG-derived hydr...

Selenoprotein P (SeP), serving as selenium transporter and extracellular antioxidant, is assumed to have a protective role in the gastrointestinal tract, which is particularly susceptible to oxidative damage. Decreased SeP mRNA levels have been found in colon cancer; however, information on the control of intestinal SeP biosynthesis is scarce. We a...

Coccidiosis with the protozoan parasite Eimeria as the infectious agent causes enormous economic losses, particularly in poultry farms. Here, we investigated the effects of garlic on the outcome of coccidiosis caused by Eimeria papillata in male Balb/c mice. The data showed that mice infected with E. papillata revealed an output of 3260 ± 680 oocys...

The heat shock response is a highly conserved process essential for surviving environmental stress, including extremes of temperature. To investigate whether heat shock has an impact on intracellular Zn(2+) homeostasis, cells were subjected to heat shock, and subsequently the intracellular free zinc concentration was investigated. Sublethal heat sh...

It is not known whether the association between increased plasma homocysteine (Hcy) associated with LDL modification and propensity for LDL uptake by macrophages in cardiovascular disease patients holds true in vascular dementia (VaD). Plasma from 83 subjects diagnosed with Alzheimer's disease (AD), VaD, mild cognitive impairment (MCI) and from con...

Oxidative stress pervades the chemical, biological, biochemical, and clinical-medical literature. The apparently simple concept of an imbalance between oxidants and antioxidants, potentially leading to molecular damage, has evolved in recent years to focus on biological responses, including a disruption of redox signaling and control. Related terms...

The extended abstracts in this report are based on presentations from the 12(th) Special Conference on Functional Foods for Health Promotion, cosponsored by the North American branch of the International Life Sciences Institute (ILSI North America) Project Committee on Flavonoids and the American Society for Nutrition at the Experimental Biology me...

Unlabelled: Gap junctional intercellular communication (GJIC) plays a critical role in the regulation of tissue homeostasis and carcinogenesis and is modulated by the levels, subcellular localization, and posttranslational modification of gap junction proteins, the connexins (Cx). Here, using oval cell-like rat liver epithelial cells, we demonstra...

High serum selenium levels have been associated epidemiologically with increased incidence of type 2 diabetes. The major fraction of total selenium in serum is represented by liver-derived selenoprotein P (SeP). This study was undertaken to test for a hypothesized effect of hyperglycemia and the antihyperglycemic drug metformin on hepatic selenopro...

A higher daily intake of fruits and vegetables in healthy elderly is associated with an improved antioxidant status in comparison to subjects consuming diets poor in fruits and vegetables, but the impact on cognitive performance is unclear. Healthy community dwellers (45 to 102 years old, n=193) underwent cognitive testing and blood withdrawal for...

IntroductionMolecular Oxygen and Reactive Oxygen Species: Biochemical Relations and Endogenous SourcesGeneration of Oxidative Stress Under the Influence of Xenobiotics and Stressful StimuliReferences

Reactive oxygen species (ROS) are derived from cellular oxygen metabolism and from exogenous sources. An excess of ROS results in oxidative stress and may eventually cause cell death. ROS levels within cells and in extracellular body fluids are controlled by concerted action of enzymatic and non-enzymatic antioxidants. The essential trace element s...

To explore the effects of increasing fruit and vegetable intake and the resulting effects on levels of circulating micronutrients in a community-dwelling population with an already high consumption of fruits and vegetables, 112 volunteers (86% women) underwent targeted dietary counseling for three months. At the beginning of the study and after 4,...

No Abstract available.

Unlabelled: Selenoprotein P (SeP), the major selenoprotein in plasma, is produced mainly by the liver, although SeP expression is detected in many organs. Recently, we reported stimulation of SeP promoter activity by the forkhead box transcription factor FoxO1a in hepatoma cells and its attenuation by insulin. Here, we demonstrate that this transl...

Carotenoids are used for systemic photoprotection in humans. Regarding mechanisms underlying photoprotective effects of carotenoids, here we compared the modulation of UVA-related injury by carotenoids. Human dermal fibroblasts (HDF) were exposed to moderate doses of UVA, which stimulated apoptosis, increased levels of reactive oxygen species and t...

No Abstract available.

Ingestion of selected nutrients modulates dermal properties. In the present study, two groups of women ingested flaxseed or borage oil for 12 weeks. The control group received a placebo containing medium-chain fatty acids. Dose was 2.2 g total fatty acids/d with alpha-linolenic acid and linoleic acid as major constituents in the flaxseed oil group;...

(-)-Epicatechin is a dietary polyphenol exerting beneficial effects on the cardiovascular system as judged from epidemiological and clinical studies. Cocoa products, red wine as well as green and black tea are most prominent sources for (-)-epicatechin and related flavan-3-ols. The possible contribution of beer still remains to be substantiated. Co...

Apocynin has been reported to require dimerization by myeloperoxidase (MPO) to inhibit leukocyte NADPH oxidase. (-)-Epicatechin, a dietary flavan-3-ol, has been identified as a 'prodrug' of apocynin-like metabolites that inhibit endothelial NADPH oxidase activity and elevate the cellular level of nitric oxide. Since (-)-epicatechin has tentatively...

Changes of the redox balance in cells alter the availability of intracellular free Zn(2+). Here, cells were exposed to ultraviolet (UV)-A, UV-B, or infrared (IR)-A light irradiation, and the intracellular free zinc pool was monitored. Under sublethal conditions only UV-A irradiation resulted in a transient cytoplasmic and nuclear increase of intrac...