Hydrogen sulfide, oxygen, and calcium regulation in developing human airway smooth muscle

Colleen M. Bartman, Marta Schiliro, Martin Helan, Y. S. Prakash, David Linden, Christina Pabelick

Research output: Contribution to journalArticle

Abstract

Preterm infants can develop airway hyperreactivity and impaired bronchodilation following supplemental O2 (hyperoxia) in early life, making it important to understand mechanisms of hyperoxia effects. Endogenous hydrogen sulfide (H2S) has anti-inflammatory and vasodilatory effects with oxidative stress. There is little understanding of H2S signaling in developing airways. We hypothesized that the endogenous H2S system is detrimentally influenced by O2 and conversely H2S signaling pathways can be leveraged to attenuate deleterious effects of O2. Using human fetal airway smooth muscle (fASM) cells, we investigated baseline expression of endogenous H2S machinery, and effects of exogenous H2S donors NaHS and GYY4137 in the context of moderate hyperoxia, with intracellular calcium regulation as a readout of contractility. Biochemical pathways for endogenous H2S generation and catabolism are present in fASM, and are differentially sensitive to O2 toward overall reduction in H2S levels. H2S donors have downstream effects of reducing [Ca2+]i responses to bronchoconstrictor agonist via blunted plasma membrane Ca2+ influx: effects blocked by O2. However, such detrimental O2 effects are targetable by exogenous H2S donors such as NaHS and GYY4137. These data provide novel information regarding the potential for H2S to act as a bronchodilator in developing airways in the context of oxygen exposure.

Original languageEnglish (US)
Pages (from-to)12991-13004
Number of pages14
JournalFASEB Journal
Volume34
Issue number9
DOIs
StatePublished - Sep 1 2020

Keywords

  • calcium
  • contractility
  • fetal airway
  • oxygen
  • prematurity

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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