Antioxidant Defense by Thioredoxin Can Occur Independently of Canonical Thiol-Disulfide Oxidoreductase Enzymatic Activity

Abstract

Summary The thiol-disulfide oxidoreductase CXXC catalytic domain of thioredoxin contributes to antioxidant defense in phylogenetically diverse organisms. We find that while the oxidoreductase activity of thioredoxin-1 protects Salmonella enterica serovar Typhimurium from hydrogen peroxide in vitro, it does not appear to contribute to Salmonella’s antioxidant defenses in vivo. Nonetheless, thioredoxin-1 defends Salmonella from oxidative stress resulting from NADPH phagocyte oxidase macrophage expression during the innate immune response in mice. Thioredoxin-1 binds to the flexible linker, which connects the receiver and effector domains of SsrB, thereby keeping this response regulator in the soluble fraction. Thioredoxin-1, independently of thiol-disulfide exchange, activates intracellular SPI2 gene transcription required for Salmonella resistance to both reactive species generated by NADPH phagocyte oxidase and oxygen-independent lysosomal host defenses. These findings suggest that the horizontally-acquired virulence determinant SsrB is regulated post-translationally by ancestrally-present thioredoxin.

Divergent Synthesis of Disulfanes and Benzenesulfonothioates Bearing 2‐Aminofurans From N‐Tosylhydrazone‐Bearing Thiocarbamates

“…On the basis of the preliminary mechanistic studies and precedented reports, [12,22] ap lausible cyclization pathway is proposed in Scheme 7. First, 1a undergoes carbene formation in the presence of acopper salt and base,thus leading to the intermediate A.T hiocarbamate attack on the carbene forms an S-containing three-membered ring intermediate (B), which produces aryl thiophenol E by ring-opening, [1,2]-H shift, and tautomerism. Thed imerization of E gives 2a,a nd the Ts anion released from N-tosylhydrazone can further serve as anucleophile to facilitate the formation of 3a.…”

“…Disulfanes,animportant class of molecules containing asulfur-sulfur framework, which exists in nature, [1] have been widely employed in biochemistry, [2] food chemistry, [3] and the pharmaceutical industry, [4] as well as substrates for generating more complex sulfur-sulfur-containing molecules. [5] Among them, disulfane-bearing 2-aminofuran frameworks are particularly attractive since they are common structural motifs in many bioactive natural products and pharmaceutical entities [6] (Scheme 1).…”

Modulation of Oxidative Stress by Abhrak Bhasma in Drosophila Melanogaster

“…Glutathione system, thioredoxin system, and vitamins are some of the major non-catalytic components that target the free radicals in non-specific manner [5][6][7]. The catalytic antioxidant machinery mainly involves constitutive and/or induced enzyme systems that target specific free radicals.…”

Caryophyllane Thiols, Vinyl Thioethers, Di‐ and Bis‐Sulfides: Antioxidant and Membrane Protective Activities

“…It is known that sulfur‐containing compounds play an important role in the formation of protective systems of an organism. For example, the thiol‐disulfide oxireductase CXXC catalytic domain of thioredoxin is used by many redox proteins for formation, isomerization, and reduction of disulfide bonds and for other redox functions . Glutathione system involved in thiol‐disulfide redox equilibrium has similar functions, thereby protecting the organisms against the effects of free radicals …”

“…Previously, we have synthesized [(1R,4R,6R,9R,10S)-4,12,12-trimethyl-5-oxatricyclo[8.2.0.0 4,6 ]dodecan-9-yl]methanethiol (1), [31] (1R,4R,6R,9R,10S,1 0 R,4 0 R,6 0 R,9 0 R,10 0 S)-9,9 0 -(disulfanediyldimethanediyl)bis(4,12,12-trimethyl-5oxatricyclo[8.2.0.0 4,6 ]dodecane) (2), [32] (1R,4R,6R,9R,10S)-9-[(ethenylsulfanyl)methyl]-4,12,12-trimethyl-5-oxatri-cyclo[8.2.0.0 4,6 ]dodecane (3), [32] (1R,4R,6R,9R,10S,1 0 R, 4 0 R,6 0 R,9 0 R,10 0 S)-9,9 0 -[(Z)-ethene-1,2-diylbis(sulfanediylmethanediyl)]bis(4,12,12-trimethyl-5-oxatricyclo[8.2.0.0 4,6 ]dodecane) (4), [32] and (1R,3Z,5R,8R,9S)-4,11,11-trimethyl-8-(sulfanylmethyl)bicyclo[7.2.0]undec-3-en-5-ol (5). [33] To determine the effect of the sesquiterpene fragment, and double and disulfide bonds on biological activity, we synthesized bis-sulfides with thioterpenic fragments separated by ethylene and vinylene linkers and sesquiterpene sulfides with vinyl groups and studied the antioxidant, membrane protective and radical scavenging activities of all obtained compounds.…”