Inhibition of Mitochondrial Bioenergetics by Esterase-Triggered COS/H2S Donors

Andrea K. Steiger, Michela Marcatti, Csaba Szabo, Bartosz Szczesny, Michael D. Pluth

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Hydrogen sulfide (H2S) is an important biological mediator, and synthetic H2S donating molecules provide an important class of investigative tools for H2S research. Here, we report esterase-activated H2S donors that function by first releasing carbonyl sulfide (COS), which is rapidly converted to H2S by the ubiquitous enzyme carbonic anhydrase (CA). We report the synthesis, self-immolative decomposition, and H2S release profiles of the developed scaffolds. In addition, the developed esterase-triggered COS/H2S donors exhibit higher levels of cytotoxicity than equivalent levels of Na2S or the common H2S donors GYY4137 and AP39. Using cellular bioenergetics measurements, we establish that the developed donors reduce cellular respiration and ATP synthesis in BEAS 2B human lung epithelial cells, which is consistent with COS/H2S inhibition of cytochrome c oxidase in the mitochondrial respiratory chain although not observed with common H2S donors at the same concentrations. Taken together, these results may suggest that COS functions differently than H2S in certain biological contexts or that the developed donors are more efficient at delivering H2S than other common H2S-releasing motifs.

Original languageEnglish (US)
Pages (from-to)2117-2123
Number of pages7
JournalACS Chemical Biology
Volume12
Issue number8
DOIs
StatePublished - Aug 18 2017

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Esterases
Energy Metabolism
Cell Respiration
Hydrogen Sulfide
Carbonic Anhydrases
Electron Transport Complex IV
Cytotoxicity
Electron Transport
Scaffolds
Self Report
Adenosine Triphosphate
Epithelial Cells
Decomposition
Lung
Molecules
carbonyl sulfide
Enzymes
Research

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

Cite this

Inhibition of Mitochondrial Bioenergetics by Esterase-Triggered COS/H2S Donors. / Steiger, Andrea K.; Marcatti, Michela; Szabo, Csaba; Szczesny, Bartosz; Pluth, Michael D.

In: ACS Chemical Biology, Vol. 12, No. 8, 18.08.2017, p. 2117-2123.

Research output: Contribution to journalArticle

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