Alleviating cellular oxidative stress through treatment with superoxide-triggered persulfide prodrugs
| Autor: | Ethan W. Winckler, John B. Matson, Yin Wang, Kearsley M. Dillon, Zhao Li |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Peptide
Sulfides 010402 general chemistry medicine.disease_cause 01 natural sciences Catalysis Article Cell Line chemistry.chemical_compound Mice Superoxides medicine Animals Prodrugs Hydrogen Sulfide Overproduction chemistry.chemical_classification Reactive oxygen species Molecular Structure 010405 organic chemistry Superoxide Optical Imaging General Medicine General Chemistry In vitro 0104 chemical sciences Rats Oxidative Stress RAW 264.7 Cells chemistry Biochemistry Phorbol Oxidative stress Cysteine |
| Zdroj: | Angew Chem Int Ed Engl |
| Popis: | Overproduction of superoxide anion (O(2)∙(−)), the primary cellular reactive oxygen species (ROS), is implicated in various human diseases. To reduce cellular oxidative stress caused by overproduction of superoxide, we developed a compound that reacts with O(2)∙(−) to release a persulfide (RSSH), a type of reactive sulfur species related to the gasotransmitter hydrogen sulfide (H(2)S). Termed SOPD-NAC, this persulfide donor reacts specifically with O(2)∙(−), decomposing to generate N-acetyl cysteine (NAC) persulfide. To enhance persulfide delivery to cells, we conjugated the SOPD motif to a short, self-assembling peptide (Bz-CFFE-NH(2)) to make a superoxide-responsive, persulfide-donating peptide (SOPD-Pep). Both SOPD-NAC and SOPD-Pep delivered persulfides/H(2)S to H9C2 cardiomyocytes and lowered ROS levels as confirmed by quantitative in vitro fluorescence imaging studies. Additional in vitro studies on RAW 264.7 macrophages showed that SOPD-Pep mitigated toxicity induced by phorbol 12-myristate 13-acetate (PMA) more effectively than SOPD-NAC and several control compounds, including common H(2)S donors. |
| Databáze: | OpenAIRE |
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