scholarly journals Selenomethionine: A Pink Trojan Redox Horse with Implications in Aging and Various Age-Related Diseases

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 882
Author(s):  
Muhammad Jawad Nasim ◽  
Mhd Mouayad Zuraik ◽  
Ahmad Yaman Abdin ◽  
Yannick Ney ◽  
Claus Jacob
Keyword(s):  
Mammalian Cells ◽  
Active Metabolites ◽  
Selenium Compounds ◽  
Redox Biology ◽  
Physiological Conditions ◽  
Organic Selenium ◽  
Age Related ◽  
Redox Active ◽  
Aging Health ◽  
Sulfur Analog

Selenium is an essential trace element. Although this chalcogen forms a wide variety of compounds, there are surprisingly few small-molecule organic selenium compounds (OSeCs) in biology. Besides its more prominent relative selenocysteine (SeCys), the amino acid selenomethionine (SeMet) is one example. SeMet is synthesized in plants and some fungi and, via nutrition, finds its way into mammalian cells. In contrast to its sulfur analog methionine (Met), SeMet is extraordinarily redox active under physiological conditions and via its catalytic selenide (RSeR’)/selenoxide (RSe(O)R’) couple provides protection against reactive oxygen species (ROS) and other possibly harmful oxidants. In contrast to SeCys, which is incorporated via an eloquent ribosomal mechanism, SeMet can enter such biomolecules by simply replacing proteinogenic Met. Interestingly, eukaryotes, such as yeast and mammals, also metabolize SeMet to a small family of reactive selenium species (RSeS). Together, SeMet, proteins containing SeMet and metabolites of SeMet form a powerful triad of redox-active metabolites with a plethora of biological implications. In any case, SeMet and its family of natural RSeS provide plenty of opportunities for studies in the fields of nutrition, aging, health and redox biology.

scholarly journals Understanding the Redox Biology of Selenium in the Search of Targeted Cancer Therapies

Antioxidants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 420 ◽  
Author(s):  
Jeffrey M. Stolwijk ◽  
Rohan Garje ◽  
Jessica C. Sieren ◽  
Garry R. Buettner ◽  
Yousef Zakharia
Keyword(s):  
Selenium Deficiency ◽  
Vital Role ◽  
High Dose ◽  
Specific Cell ◽  
Cancer Therapies ◽  
Selenium Compounds ◽  
Redox Biology ◽  
Selenium Treatment ◽  
Prevention Of Cancer

Selenium (Se) is an essential trace nutrient required for optimal human health. It has long been suggested that selenium has anti-cancer properties. However, clinical trials have shown inconclusive results on the potential of Se to prevent cancer. The suggested role of Se in the prevention of cancer is centered around its role as an antioxidant. Recently, the potential of selenium as a drug rather than a supplement has been uncovered. Selenium compounds can generate reactive oxygen species that could enhance the treatment of cancer. Transformed cells have high oxidative distress. As normal cells have a greater capacity to meet oxidative challenges than tumor cells, increasing the flux of oxidants with high dose selenium treatment could result in cancer-specific cell killing. If the availability of Se is limited, supplementation of Se can increase the expression and activities of Se-dependent proteins and enzymes. In cell culture, selenium deficiency is often overlooked. We review the importance of achieving normal selenium biology and how Se deficiency can lead to adverse effects. We examine the vital role of selenium in the prevention and treatment of cancer. Finally, we examine the properties of Se-compounds to better understand how each can be used to address different research questions.

scholarly journals Secreted CXCL12 (SDF-1) forms dimers under physiological conditions

2012 ◽  
Vol 442 (2) ◽  
pp. 433-442 ◽  
Author(s):  
Paramita Ray ◽  
Sarah A. Lewin ◽  
Laura Anne Mihalko ◽  
Sasha-Cai Lesher-Perez ◽  
Shuichi Takayama ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Extracellular Space ◽  
Mammalian Cells ◽  
Cell Signalling ◽  
Xenograft Model ◽  
Physiological Conditions ◽  
Cxc Chemokine ◽  
Chemokine Ligand ◽  
Chemokine Cxcl12 ◽  
And Function

Chemokine CXCL12 (CXC chemokine ligand 12) signalling through CXCR (CXC chemokine receptor) 4 and CXCR7 has essential functions in development and underlies diseases including cancer, atherosclerosis and autoimmunity. Chemokines may form homodimers that regulate receptor binding and signalling, but previous studies with synthetic CXCL12 have produced conflicting evidence for homodimerization. We used bioluminescence imaging with GL (Gaussia luciferase) fusions to investigate dimerization of CXCL12 secreted from mammalian cells. Using column chromatography and GL complementation, we established that CXCL12 was secreted from mammalian cells as both monomers and dimers. Secreted CXCL12 also formed homodimers in the extracellular space. Monomeric CXCL12 preferentially activated CXCR4 signalling through Gαi and Akt, whereas dimeric CXCL12 more effectively promoted recruitment of β-arrestin 2 to CXCR4 and chemotaxis of CXCR4-expressing breast cancer cells. We also showed that CXCR7 preferentially sequestered monomeric CXCL12 from the extracellular space and had minimal effects on dimeric CXCL12 in cell-based assays and an orthotopic tumour xenograft model of human breast cancer. These studies establish that CXCL12 secreted from mammalian cells forms homodimers under physiological conditions. Since monomeric and dimeric CXCL12 have distinct effects on cell signalling and function, our results have important implications for ongoing efforts to target CXCL12 pathways for therapy.

scholarly journals Redox Index of Cys-Thiol Residues of Serum Apolipoprotein E and Its Diagnostic Potential

2021 ◽  
Author(s):  
Kazuyoshi Yamauchi ◽  
Yasushi Kawakami
Keyword(s):  
Apolipoprotein E ◽  
Serum Triglyceride ◽  
Redox Status ◽  
Reduced Form ◽  
Band Shift ◽  
Redox Biology ◽  
Age Related ◽  
Diagnostic Potential ◽  
The Difference ◽  
Hba1c Levels

Abstract We explored the proper index for estimating the redox status of Cys-thiol of serum apolipoprotein E (apoE), named “redox-IDX-apoE,” which is necessary to understand the redox biology of age-related diseases, such as atherosclerosis. The fractions of reduced form (red-), reversible oxidized form (roxi-), and irreversibly oxidized form (oxi-) apoE were measured by a band-shift assay. Candidates of redox-IDX-apoE were determined by calculating the values of these fractions and total apoE concentration. The ratios of roxi-apoE to total-apoE (roxi/total), red-apoE to roxi-apoE (red/roxi), and [red-apoE + oxi-apoE] to roxi-apoE ([red + oxi]/roxi) were independent of age and sex. Roxi/total showed significant negative correlations with serum triglyceride (TG) and HbA1c levels, while red/roxi and [red + oxi]/roxi showed significant positive correlations with them. However, red/roxi and [red + oxi]/roxi in the patients with atherosclerosis were significantly lower than those in control subjects, although serum TG and HbA1c levels in the patients were significantly higher than those in controls. The redox status of serum apoE-Cys-thiol is closely involved in the metabolism of TG-rich lipoproteins and glucose and may vary depending on the difference in pathological conditions. The appropriate usage of these ratios could be helpful in the diagnosis and prognosis of age-related diseases.

scholarly journals Aromatic Selenocyanates as a New Class of Non-Mutagenic Antimicrobial Selenium Compounds with Pronounced Activity against Multidrug Resistant ESKAPE Bacteria

2018 ◽  
Author(s):  
Muhammad Jawad Nasim ◽  
Karolina Witek ◽  
Annamaria Kincses ◽  
Muhammad Sarfraz ◽  
Ewa Żesławska ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Multidrug Resistant ◽  
Synthetic Chemistry ◽  
High Biological Activity ◽  
Selenium Compounds ◽  
X Ray Crystallography ◽  
Organic Selenium ◽  
Interesting Class ◽  
Mrsa Strains

Selenocyanates form an interesting class of organic selenium compounds as they serve as multifunctional agents (being the precursors of seleninic acids and diselenides in synthetic chemistry and as antimicrobial and cytotoxic agent in biology) and, due to their similarity with better known thiocyanates promise high biological activity. Yet whilst selenocyanates are common in synthetic chemistry, they are rarely considered in pharmaceutical design. Arylmethyl selenocyanates (1-13) have been synthesized and an insight into their structural properties using X-ray crystallography has been obtained. The compounds subsequently have been evaluated for their potential antimicrobial, nematicidal and cytotoxic activity. ADMET properties in vitro, using mutagenicity (AMES) and permeability (PAMPA) tests, have been determined. The compounds exhibit pronounced activity against various strains of bacteria (both Gram-positive and Gram-negative) and yeasts. Among them, benzylselenocyanate (1) represents the most active anti-ESKAPE agent, with potent antibacterial activity, especially against multidrug resistant MRSA strains (HEMSA 5). Our results demonstrate that the arylmethyl selenocyantes are not only non-mutagenic but also possess moderate cytotoxic activity against cancer cells.

scholarly journals Organic selenium compounds as potential chemotherapeutic agents for improved cancer treatment

2018 ◽  
Vol 127 ◽  
pp. 80-97 ◽  
Author(s):  
Valentina Gandin ◽  
Prajakta Khalkar ◽  
Jeremy Braude ◽  
Aristi P. Fernandes
Keyword(s):  
Cancer Treatment ◽  
Chemotherapeutic Agents ◽  
Selenium Compounds ◽  
Organic Selenium

Biotransformation of organic selenium compounds in budding yeast,Saccharomyces cerevisiae

Metallomics ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1257-1263 ◽  
Author(s):  
Yasumitsu Ogra ◽  
Maya Shimizu ◽  
Kazuaki Takahashi ◽  
Yasumi Anan
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Budding Yeast ◽  
Yeast Saccharomyces Cerevisiae ◽  
Selenium Compounds ◽  
Organic Selenium ◽  
Selenoamino Acids

Organic selenium metabolites of plants and animals such as selenoamino acids and selenosugars are metabolized to selenomethionine in yeast.

Abstract 123: Age-Related Endothelial Senescence is Driven by Thrombospondin-1-Activated NADPH Oxidase Nox1

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Daniel N Meijles ◽  
Imad Al Ghouleh ◽  
Sanghamitra Sahoo ◽  
Jefferson H Amaral ◽  
Heather Knupp ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Vascular Diseases ◽  
Dependent Manner ◽  
Wild Type ◽  
Molecular Control ◽  
Redox Biology ◽  
Age Related ◽  
P53 Activation

Organismal aging represents an independent risk factor underlying many vascular diseases, including systemic and pulmonary hypertension, and atherosclerosis. While the mechanisms driving aging are largely elusive, a steady persistent increase in tissue oxidative stress has been associated with senescence. Previously we showed TSP1 elicits NADPH oxidase (Nox)-dependent vascular smooth muscle cell oxidative stress. However mechanisms by which TSP1 affects endothelial redox biology are unknown. Here, we tested the hypothesis that TSP1 induces endothelial oxidative stress-linked senescence in aging. Using rapid autopsy disease-free human pulmonary (PA) artery, we identified a significant positive correlation between age, protein levels of TSP1, Nox1 and the cell-cycle repressor p21cip (p<0.05). Age also positively associated with increased Amplex Red-detected PA hydrogen peroxide levels (p<0.05). Moreover, treatment of human PA endothelial cells (HPAEC) with TSP1 (2.2nM; 24h) increased expression (~1.9 fold; p<0.05) and activation of Nox1 (~1.7 fold; p<0.05) compared to control, as assessed by Western blot and SOD-inhibitable cytochrome c reduction. Western blotting and immunofluorescence showed a TSP1-mediated increase in p53 activation, indicative of the DNA damage response. Moreover, TSP1 significantly increased HPAEC senescence in a p53/p21cip/Rb-dependent manner, as assessed by immunofluorescent detection of subcellular localization and senescence-associated β-galactosidase staining. To explore this pathway in vivo, middle-aged (8-10 month) wild-type and TSP1-null mice were utilized. In the TSP1-null, reduced lung senescence, oxidative stress, Nox1 levels and p21cip expression were observed compared to wild-type supporting findings in human samples and cell experiments. Finally, prophylactic treatment with specific Nox1 inhibitor NoxA1ds (10μM) attenuated TSP1-induced HPAEC ROS, p53 activation, p21cip expression and senescence. Taken together, our results provide molecular insight into the functional interplay between TSP1 and Nox1 in the regulation of endothelial senescence, with implications for molecular control of the aging process.

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