cb7b00279_si_001.pdf (535.77 kB)
Inhibition of Mitochondrial Bioenergetics by Esterase-Triggered COS/H2S Donors
journal contribution
posted on 2017-06-14, 00:00 authored by Andrea
K. Steiger, Michela Marcatti, Csaba Szabo, Bartosz Szczesny, Michael D. PluthHydrogen
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.
History
Usage metrics
Categories
Keywords
COS functionsequivalent levelsH 2 S donors GYY 4137AP 39.H 2 S release profilescytochrome c oxidaseH 2 S donorsenzyme carbonic anhydraseMitochondrial BioenergeticsCAH 2 Sbioenergetics measurementsH 2 S-releasing motifsBEAS 2 Bcarbonyl sulfideself-immolative decompositionlung epithelial cellsNa 2 SATP synthesisH 2 S researchreport esterase-activated H 2 S donors
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC