Biological Chemistry of Hydrogen Selenide

Cupp‐Sutton, Kellye A.; Ashby, Michael T.

doi:10.3390/antiox5040042

Cited by 80 publications

(72 citation statements)

References 160 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In dynamic contexts like cells and blood circulation, downstream selenol metabolites might be present including methyl selenol and hydrogen selenide 34 . The high reactivity of selenol per se leads to low abundance at steady state and challenges direct measurement 26 .…”

Section: Discussionmentioning

confidence: 99%

A general covalent binding model between cytotoxic selenocompounds and albumin revealed by mass spectrometry and X-ray absorption spectroscopy

Zheng

Boada

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Selenocompounds (Secs) are promising therapeutic agents for a wide range of diseases including cancer. the treatment results are heterogeneous and dependent on both the chemical species and the concentration of SeCs. Moreover, the mechanisms of action are poorly revealed, which most probably is due to the detection methods where the quantification is based on the total selenium as an element. To understand the mechanisms underlying the heterogeneous cytotoxicity of Secs and to determine their pharmacokinetics, we investigated selenium speciation of six SeCs representing different categories using liquid chromatography-mass spectrometry (LC-MS) and X-ray absorption spectroscopy (XAS) and the cytotoxicity using leukemic cells. Secs cytotoxicity was correlated with albumin binding degree as revealed by LC-MS and XAS. Further analysis corroborated the covalent binding between selenol intermediates of SeCs and albumin thiols. On basis of the Se-S model, pharmacokinetic properties of four SeCs were for the first time profiled. In summary, we have shown that cytotoxic SeCs could spontaneously transform into selenol intermediates that immediately react with albumin thiols through Se-S bond. the heterogeneous albumin binding degree may predict the variability in cytotoxicity. the present knowledge will also guide further kinetic and mechanistic investigations in both experimental and clinical settings.Selenocompounds (SeCs) refer to the inorganic and organic compounds containing the selenium (Se) element. Currently, a great number of SeCs are being used in preclinical and clinical investigations. On basis of the inverse relationship between selenium abundance in vivo and risk of cancer revealed by observational studies 1 , several clinical trials are ongoing to assess cancer-preventive role of SeCs in human 2-5 . SeCs are also applied to attenuate toxicity from environmental pollutants like arsenic trioxide and improve the health status 6,7 . The rationale behind these applications is largely attributed to the antioxidant functions of selenoproteins, which utilize selenium as a key element in form of selenocysteine. In contrast, SeCs at doses exceeding nutritional level could produce abundant concentrations of reactive oxygen species that induce oxidative damage. The oxitative stress has been utilized in several indications including malignancy, malaria and bacterial infections 8,9 . Interestingly, upregulation of antioxidant status has been identified to underly chemoresistance in cancer, thus the use of SeCs could re-sensitize resistant cancer cells to chemotherapy 10,11 . Noteworthy, the profound effects of SeCs are further encouraging endeavors to improve the efficacy of existing small molecule drugs and antibodies by incorporating selenium element 12,13 .

show abstract

Section: Discussionmentioning

confidence: 99%

A general covalent binding model between cytotoxic selenocompounds and albumin revealed by mass spectrometry and X-ray absorption spectroscopy

Zheng

Boada

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Selenium is an essential micronutrient with similar chemical and physical properties to sulfur, but more easily oxidized and kinetically more labile than sulfur. Selenium is a component of proteinogenic selenocysteine, naturally occurring selenomethionine and selenoproteins, such as glutathione peroxidase (GPx), thioredoxin reductase (TRXR), and selenoprotein P [ 57 ]. Reactive selenium species (RSeS) are selenium-containing inorganic and organic compounds including selenite (O 3 Se −2 ), selenocysteine (C 3 H 7 NO 2 Se), and selenomethionine (C 5 H 11 NO 2 Se) [ 58 ] ( Table 2 ).…”

Section: Oxidative Stressmentioning

confidence: 99%

Monitoring the Redox Status in Multiple Sclerosis

Tanaka

Vécsei

2020

Biomedicines

View full text Add to dashboard Cite

Worldwide, over 2.2 million people suffer from multiple sclerosis (MS), a multifactorial demyelinating disease of the central nervous system. MS is characterized by a wide range of motor, autonomic, and psychobehavioral symptoms, including depression, anxiety, and dementia. The blood, cerebrospinal fluid, and postmortem brain samples of MS patients provide evidence on the disturbance of reduction-oxidation (redox) homeostasis, such as the alterations of oxidative and antioxidative enzyme activities and the presence of degradation products. This review article discusses the components of redox homeostasis, including reactive chemical species, oxidative enzymes, antioxidative enzymes, and degradation products. The reactive chemical species cover frequently discussed reactive oxygen/nitrogen species, infrequently featured reactive chemicals such as sulfur, carbonyl, halogen, selenium, and nucleophilic species that potentially act as reductive, as well as pro-oxidative stressors. The antioxidative enzyme systems cover the nuclear factor erythroid-2-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 (KEAP1) signaling pathway. The NRF2 and other transcriptional factors potentially become a biomarker sensitive to the initial phase of oxidative stress. Altered components of the redox homeostasis in MS were discussed in search of a diagnostic, prognostic, predictive, and/or therapeutic biomarker. Finally, monitoring the battery of reactive chemical species, oxidative enzymes, antioxidative enzymes, and degradation products helps to evaluate the redox status of MS patients to expedite the building of personalized treatment plans for the sake of a better quality of life.

show abstract

“…As a consequence, at physiological pH, reduced SeCys exists as a selenolate ion (RSe − ) whereas cysteine is mostly protonated. This property, as well as the higher nucleophilicity of the selenolate, contributes to the greater reactivity of SeCys over cysteine in redox reactions (108)(109)(110). Thus, for example, a SeCys to cysteine substitution reduces 300 times the catalytic efficiency of the Escherichia coli selenoenzyme formate dehydrogenase (111).…”

Section: Selenocyst(e)ine Toxicitymentioning

confidence: 99%

Recent advances in the mechanism of selenoamino acids toxicity in eukaryotic cells

Lazard

Dauplais

Blanquet

et al. 2017

Biomolecular Concepts

View full text Add to dashboard Cite

Selenium is an essential trace element due to its incorporation into selenoproteins with important biological functions. However, at high doses it is toxic. Selenium toxicity is generally attributed to the induction of oxidative stress. However, it has become apparent that the mode of action of seleno-compounds varies, depending on its chemical form and speciation. Recent studies in various eukaryotic systems, in particular the model organism Saccharomyces cerevisiae, provide new insights on the cytotoxic mechanisms of selenomethionine and selenocysteine. This review first summarizes current knowledge on reactive oxygen species (ROS)-induced genotoxicity of inorganic selenium species. Then, we discuss recent advances on our understanding of the molecular mechanisms of selenocysteine and selenomethionine cytotoxicity. We present evidences indicating that both oxidative stress and ROSindependent mechanisms contribute to selenoamino acids cytotoxicity. These latter mechanisms include disruption of protein homeostasis by selenocysteine misincorporation in proteins and/or reaction of selenols with protein thiols.

show abstract

Biological Chemistry of Hydrogen Selenide

Cited by 80 publications

References 160 publications

A general covalent binding model between cytotoxic selenocompounds and albumin revealed by mass spectrometry and X-ray absorption spectroscopy

A general covalent binding model between cytotoxic selenocompounds and albumin revealed by mass spectrometry and X-ray absorption spectroscopy

Monitoring the Redox Status in Multiple Sclerosis

Recent advances in the mechanism of selenoamino acids toxicity in eukaryotic cells

Contact Info

Product

Resources

About