Human serum albumin hydropersulfide is a potent reactive oxygen species scavenger in oxidative stress conditions such as chronic kidney disease

Shibata, Akitomo; Ishima, Yu; Ikeda, Mayumi; Sato, Hírokazu; Imafuku, Tadashi; Chuang, Victor Tuan Giam; Ouchi, Yuya; Abe, Takaya; Watanabe, Hiroshi; Ishida, Tatsuhiro; Otagiri, Masaki; Maruyama, Toru

doi:10.1016/j.bbrc.2016.09.113

Cited by 26 publications

(14 citation statements)

References 19 publications

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“…46,55 Several studies have speculated that intracellular RSSH and related species protect cells from oxidative stress. 5,6,8,9,[18][19][20]23 We sought to determine whether our alkylamine-substituted perthiocarbamates exert protective effects against oxidative stress and myocardial ischemia-reperfusion (I/R) injury. The medium-lived precursor 7b (t 1/2 = 16.7 min) was chosen for the studies.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…RSSH display distinct chemistry, and this may be important for their biological utility. For example, RSSH are superior nucleophiles and more potent reductants than their corresponding thiols because of the presence of unshared electron pairs on the sulfur atom adjacent to the nucleophilic sulfur atom. − RSSH and related species have been proposed to behave as potent antioxidants and redox signaling intermediates. ,,,,− Recent reports have demonstrated that RSSH are efficient H atom transfer agents toward alkyl, alkoxyl, peroxyl, and thiyl radicals, confirming their promise as potent antioxidants. , Unlike thiols, RSSH can also undergo transsulfuration reactions because of their electrophilic properties in the neutral state. , The sulfane sulfur in RSSH can be reversibly transferred to other free thiols such as glutathione (GSH) or cysteine (Cys-SH) to form GSSH or Cys-SSH, respectively. Furthermore, studies have suggested RSSH involvement in the detoxification of environmental electrophiles. − Yet, despite the increasing evidence of the role of RSSH in redox signaling, the biological functions of RSSH remain elusive.…”

Section: Introductionmentioning

confidence: 99%

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Alkylamine-Substituted Perthiocarbamates: Dual Precursors to Hydropersulfide and Carbonyl Sulfide with Cardioprotective Actions

et al. 2020

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The recent discovery of hydropersulfides (RSSH) in mammalian systems suggests their potential roles in cell signaling. However, the exploration of RSSH biological significance is challenging due to their instability under physiological conditions. Herein, we report the preparation, RSSH-releasing properties, and cytoprotective nature of alkylamine-substituted perthiocarbamates. Triggered by a base-sensitive, self-immolative moiety, these precursors show efficient RSSH release and also demonstrate the ability to generate carbonyl sulfide (COS) in the presence of thiols. Using this dually reactive alkylamine-substituted perthiocarbamate platform, the generation of both RSSH and COS is tunable with respect to half-life, pH, and availability of thiols. Importantly, these precursors exhibit cytoprotective effects against hydrogen peroxide-mediated toxicity in H9c2 cells and cardioprotective effects against myocardial ischemic/reperfusion injury, indicating their potential application as new RSSH- and/or COS-releasing therapeutics.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Alkylamine-Substituted Perthiocarbamates: Dual Precursors to Hydropersulfide and Carbonyl Sulfide with Cardioprotective Actions

et al. 2020

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“…The interaction of Fe 2+ and H 2 O 2 in the Fenton reaction results in the production of extremely volatile and transient hydroxyl radicals. This radical has been implicated in the oxidation of biological macromolecules (e.g., lipids, nucleic acids, and proteins) with the potential to trigger or contribute to the development and/or progression of chronic disease conditions (Chigurupati et al, ; Shibata et al, ; Treml & Šmejkal, ). Similar to the DPPH and superoxide radicals, GSH was a better scavenger of hydroxyl radicals than the FPH and peptide fractions (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Left unchecked, especially during oxidative stress‐mediated depletion of natural cellular antioxidants, such radical‐mediated injury could eventually result in chronic degenerative and debilitating diseases like hypertension, atherosclerosis, aging, cancer, diabetes mellitus, and inflammation‐related tissue damage (Chigurupati et al, ; Erdmann, Cheung, & Schröder, ; Nabha, Garbern, Buller, & Charpie, ; Treml & Šmejkal, ). For example, toxic ROS cause a wide range of biological injury to low density lipoprotein (LDL) resulting in increased atherogenicity of oxidized LDL and could also trigger or contribute to the pathological progression of cancer, atherosclerosis, Alzheimer's disease, and diabetes among others (Erdmann et al, ; Shibata et al, ; Treml & Šmejkal, ). In conditions of low levels of cellular antioxidants, supplementation with exogenous (dietary) antioxidants such as peptides could reduce the damaging effects of ROS.…”

Section: Introductionmentioning

confidence: 99%

Antioxidant Properties of Flaxseed Protein Hydrolysates: Influence of Hydrolytic Enzyme Concentration and Peptide Size

Nwachukwu

Aluko

2018

J Americ Oil Chem Soc

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Flaxseed is an emerging source of protein raw materials for bioactive protein hydrolysate production; however, there is insufficient information on the structural properties of its antioxidative peptides. The aim of this work was to determine the peptide composition and relationships to antioxidant properties of flaxseed protein hydrolysates (FPH) obtained using two protease (thermoase) concentrations (2.5 and 3.0%). The FPH were passed through ultrafiltration membranes to yield fractions with <1, 1-3, 3-5, and 5-10 kDa peptide sizes, which were also tested for antioxidant properties. Mass spectrometry data yielded several peptide sequences located within the flaxseed conlinin, but a lesser number was found in the 3.0% thermoase-FPH. 2,2-Diphenyl-1-picrylhydrazyl radical scavenging was lowest (54%) for the 3.0% thermoase-FPH while membrane separation enhanced the values up to 65% for the <1 kDa peptides. Metal chelation and iron-reducing ability were also significantly (P < 0.05) enhanced after membrane fractionation. In contrast, the hydroxyl radical scavenging ability was unchanged (2.5% thermoase-FPH) or significantly (P < 0.05) diminished (3.0% thermoase-FPH) after membrane fractionation, except for the 5-10 kDa peptides that had notably (P < 0.05) higher values. We conclude that the <1 and 1-3 kDa peptides may be useful agents to suppress oxidative stress within living tissues while the 3-5 and 5-10 kDa could be suitable preservatives to enhance food shelf life.

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“…HSA is primarily an extracellular protein (188,251), but it may reach most cells, be taken up to a certain extent, and finally be catabolized by lysosomal degradation, thus contributing to the maintenance of intracellular GSH levels. Further, recent evidence indicates that: (i) HSA is a major pool of SS (104,105,218) whose main constituent is albumin hydropersulfide, (ii) HSA hydropersulfide is a potent ROS scavenger, and (iii) there is a positive correlation between the SS content of semen and plasma.…”

Section: Systemic Effects Of H 2 S Prodrugsmentioning

confidence: 99%

SG1002 and Catenated Divalent Organic Sulfur Compounds as Promising Hydrogen Sulfide Prodrugs

Gojon¹,

Morales²

2020

Antioxidants & Redox Signaling

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Significance: Sulfur has a critical role in protein structure/function and redox status/signaling in all living organisms. Although hydrogen sulfide (H 2 S) and sulfane sulfur (SS) are now recognized as central players in physiology and pathophysiology, the full scope and depth of sulfur metabolome's impact on human health and healthy longevity has been vastly underestimated and is only starting to be grasped. Since many pathological conditions have been related to abnormally low levels of H 2 S/SS in blood and/or tissues, and are amenable to treatment by H 2 S supplementation, development of safe and efficacious H 2 S donors deserves to be undertaken with a sense of urgency; these prodrugs also hold the promise of becoming widely used for disease prevention and as antiaging agents. Recent Advances: Supramolecular tuning of the properties of well-known molecules comprising chains of sulfur atoms (diallyl trisulfide [DATS], S 8) was shown to lead to improved donors such as DATS-loaded polymeric nanoparticles and SG1002. Encouraging results in animal models have been obtained with SG1002 in heart failure, atherosclerosis, ischemic damage, and Duchenne muscular dystrophy; with TC-2153 in Alzheimer's disease, schizophrenia, age-related memory decline, fragile X syndrome, and cocaine addiction; and with DATS in brain, colon, gastric, and breast cancer. Critical Issues: Mode-of-action studies on allyl polysulfides, benzyl polysulfides, ajoene, and 12 ringsubstituted organic disulfides and thiosulfonates led several groups of researchers to conclude that the anticancer effect of these compounds is not mediated by H 2 S and is only modulated by reactive oxygen species, and that their central model of action is selective protein S-thiolation. Future Directions: SG1002 is likely to emerge as the H 2 S donor of choice for acquiring knowledge on this gasotransmitter's effects in animal models, on account of its unique ability to efficiently generate H 2 S without byproducts and in a slow and sustained mode that is dose independent and enzyme independent. Efficient tuning of H 2 S donation characteristics of DATS, dibenzyl trisulfide, and other hydrophobic H 2 S prodrugs for both oral and parenteral administration will be achieved not only by conventional structural modification of a lead molecule but also through the new ''supramolecular tuning'' paradigm. Antioxid. Redox Signal. 33, 1010-1045.

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Human serum albumin hydropersulfide is a potent reactive oxygen species scavenger in oxidative stress conditions such as chronic kidney disease

Cited by 26 publications

References 19 publications

Alkylamine-Substituted Perthiocarbamates: Dual Precursors to Hydropersulfide and Carbonyl Sulfide with Cardioprotective Actions

Alkylamine-Substituted Perthiocarbamates: Dual Precursors to Hydropersulfide and Carbonyl Sulfide with Cardioprotective Actions

Antioxidant Properties of Flaxseed Protein Hydrolysates: Influence of Hydrolytic Enzyme Concentration and Peptide Size

SG1002 and Catenated Divalent Organic Sulfur Compounds as Promising Hydrogen Sulfide Prodrugs

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