The human diet contains a great variety of natural mutagens and carcinogens, as well as many natural antimutagens and anticarcinogens. Many of these mutagens and carcinogens may act through the generation of oxygen radicals. Oxygen radicals may also play a major role as endogenous initiators of degenerative processes, such as DNA damage and mutation (and promotion), that may be related to cancer, heart disease, and aging. Dietary intake of natural antioxidants could be an important aspect of the body’s defense mechanism against these agents. Many antioxidants are being identified as anticarcinogens. Characterizing and optimizing such defense systems may be an important part of a strategy of minimizing cancer and other age-related diseases.

https://science.sciencemag.org/content/sci/221/4617/1256.full.pdf

Dietary carcinogens and anticarcinogens Oxygen radicals and degenerative diseases

Reactive oxygen species, antioxidants, and the mammalian thioredoxin system.

In the genetic code, UGA serves as a stop signal and a selenocysteine codon, but no computational methods for identifying its coding function are available. Consequently, most selenoprotein genes are misannotated. We identified selenoprotein genes in sequenced mammalian genomes by methods that rely on identification of selenocysteine insertion RNA structures, the coding potential of UGA codons, and the presence of cysteine-containing homologs. The human selenoproteome consists of 25 selenoproteins.

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Characterization of Mammalian Selenoproteomes

The goal of this review is to place the exciting advances that have occurred in our understanding of the molecular biology of the types 1, 2, and 3 (D1, D2, and D3, respectively) iodothyronine deiodinases into a biochemical and physiological context. We review new data regarding the mechanism of selenoprotein synthesis, the molecular and cellular biological properties of the individual deiodinases, including gene structure, mRNA and protein characteristics, tissue distribution, subcellular localization and topology, enzymatic properties, structure-activity relationships, and regulation of synthesis, inactivation, and degradation. These provide the background for a discussion of their role in thyroid physiology in humans and other vertebrates, including evidence that D2 plays a significant role in human plasma T3 production. We discuss the pathological role of D3 overexpression causing “consumptive hypothyroidism” as well as our current understanding of the pathophysiology of iodothyronine deiodination during illness and amiodarone therapy. Finally, we review the new insights from analysis of mice with targeted disruption of the Dio2 gene and overexpression of D2 in the myocardium. (Endocrine Reviews 23: 38–89, 2002)

Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases.

Chemistry of biologically important synthetic organoselenium compounds.

▪ Abstract Mammalian selenium-containing proteins can be divided into three groups: proteins containing nonspecifically incorporated selenium, specific selenium-binding proteins, and specific selenocysteine-containing selenoproteins Selenoproteins with known functions identified so far include five glutathione peroxidases, two deiodinases, several thioredoxin reductases, and selenophosphate synthetase 2 Alternative splicing leads to a greater variety of selenoproteins, as was shown in the cases of a specific sperm nuclei glutathione peroxidase and some thioredoxin reductases Selenoprotein P, selenoprotein W, a 15-kDa selenoprotein, an 18-kDa selenoprotein, and several selenoproteins identified in silico from nucleotide sequence databases were found to contain selenocysteine but their functions are not known Gel electrophoretic separation of tissue samples from rats labeled in vivo with 75Se showed the existence of further selenium-containing proteins

Mammalian selenium-containing proteins.

Evidence for specific selenium target tissues and new biologically important selenoproteins

Identification of type I iodothyronine 5'-deiodinase as a selenoenzyme.

SPECIFIC AIMSWe investigated the properties of a 34 kDa selenoprotein that is present only in the sperm nuclei and is highly expressed in the nuclei of late spermatids, where the reorganization and condensation of DNA take place. We performed experiments to determine the primary structure of the selenoprotein and obtain information on its functions in sperm maturation and sperm quality, especially with regard to its role in the processes of DNA condensation.PRINCIPAL FINDINGS1. A 34 kDa selenoprotein was identified as a specific sperm nuclei glutathione peroxidase (snGPx) with properties similar to phospholipid hydroperoxide glutathione peroxidase (PHGPx)By labeling rats in vivo with 75Se and separating the proteins in the tissue homogenates and subcellular fractions by SDS-PAGE, a 34 kDa selenoprotein was detected that is present only in the sperm nuclei and is highly expressed in the late spermatids. After isolation of the sonication-resistant spermatid nuclei (SRS nuclei) and treatment of their surface...

Identification of a specific sperm nuclei selenoenzyme necessary for protamine thiol cross-linking during sperm maturation

The selenium content was determined in the adrenals, brain, erythrocytes, femur, hair, heart, kidneys, lungs, muscle, pancreas, plasma, spleen, testes, and thymus of rats, which had been fed a commercial rat diet containing 03 mg Se/kg diet In the plasma, the erythrocytes, and the soluble fraction of the tissues (with the exception of femur and hair) the activity of the glutathione peroxidase (GSH-Px) was measured, using both hydrogen peroxide and t-butyl hydroperoxide as substrates From the masses of the tissues and the values for the selenium content and the GSH-Px activity, the distribution of the element and the enzyme in the body was calculated For selenium the main pools were the muscle and the liver, and for the GSH-Px, the liver and the erythrocytes By comparing the selenium content and the GSH-Px activity the percentage of the tissue selenium, which was bound to the enzyme in the soluble tissue fraction, was estimated This percentage differed considerably from tissue to tissue, the highest value being found in the erythrocytes and the smallest in the testes According to this estimation the majority of the selenium in the rat is not contained in the GSH-Px but in other compounds

Dietrich Behne

Papers

Mammalian selenium-containing proteins.

Evidence for specific selenium target tissues and new biologically important selenoproteins

Identification of type I iodothyronine 5'-deiodinase as a selenoenzyme.

Identification of a specific sperm nuclei selenoenzyme necessary for protamine thiol cross-linking during sperm maturation

Distribution of selenium and glutathione peroxidase in the rat.