Extended hypoxia-mediated H2S production provides for long-term oxygen sensing

Kenneth R. Olson, Yan Gao, Eric R. DeLeon, Troy A. Markel, Natalie Drucker, David Boone, Matt Whiteman, Andrea K. Steiger, Michael D. Pluth, Charles R. Tessier, Robert V. Stahelin

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Aim: Numerous studies have shown that H2S serves as an acute oxygen sensor in a variety of cells. We hypothesize that H2S also serves in extended oxygen sensing. Methods: Here, we compare the effects of extended exposure (24-48 hours) to varying O2 tensions on H2S and polysulphide metabolism in human embryonic kidney (HEK 293), human adenocarcinomic alveolar basal epithelial (A549), human colon cancer (HTC116), bovine pulmonary artery smooth muscle, human umbilical-derived mesenchymal stromal (stem) cells and porcine tracheal epithelium (PTE) using sulphur-specific fluorophores and fluorometry or confocal microscopy. Results: All cells continuously produced H2S in 21% O2 and H2S production was increased at lower O2 tensions. Decreasing O2 from 21% to 10%, 5% and 1% O2 progressively increased H2S production in HEK293 cells and this was partially inhibited by a combination of inhibitors of H2S biosynthesis, aminooxyacetate, propargyl glycine and compound 3. Mitochondria appeared to be the source of much of this increase in HEK 293 cells. H2S production in all other cells and PTE increased when O2 was lowered from 21% to 5% except for HTC116 cells where 1% O2 was necessary to increase H2S, presumably reflecting the hypoxic environment in vivo. Polysulphides (H2Sn, where n = 2-7), the key signalling metabolite of H2S also appeared to increase in many cells although this was often masked by high endogenous polysulphide concentrations. Conclusion: These results show that cellular H2S is increased during extended hypoxia and they suggest this is a continuously active O2-sensing mechanism in a variety of cells.

Original languageEnglish (US)
Article numbere13368
JournalActa Physiologica
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Oxygen
HEK293 Cells
Mesenchymal Stromal Cells
Swine
Epithelium
Aminooxyacetic Acid
Umbilicus
Fluorometry
Sulfur
Confocal Microscopy
Colonic Neoplasms
Glycine
Pulmonary Artery
Smooth Muscle
Hypoxia
Mitochondria
Kidney
polysulfide

Keywords

  • hypoxia
  • mitochondria
  • oxygen tension
  • sulphur metabolism

ASJC Scopus subject areas

  • Physiology

Cite this

Extended hypoxia-mediated H2S production provides for long-term oxygen sensing. / Olson, Kenneth R.; Gao, Yan; DeLeon, Eric R.; Markel, Troy A.; Drucker, Natalie; Boone, David; Whiteman, Matt; Steiger, Andrea K.; Pluth, Michael D.; Tessier, Charles R.; Stahelin, Robert V.

In: Acta Physiologica, 01.01.2019.

Research output: Contribution to journalArticle

Olson, KR, Gao, Y, DeLeon, ER, Markel, TA, Drucker, N, Boone, D, Whiteman, M, Steiger, AK, Pluth, MD, Tessier, CR & Stahelin, RV 2019, 'Extended hypoxia-mediated H2S production provides for long-term oxygen sensing', Acta Physiologica. https://doi.org/10.1111/apha.13368
Olson, Kenneth R. ; Gao, Yan ; DeLeon, Eric R. ; Markel, Troy A. ; Drucker, Natalie ; Boone, David ; Whiteman, Matt ; Steiger, Andrea K. ; Pluth, Michael D. ; Tessier, Charles R. ; Stahelin, Robert V. / Extended hypoxia-mediated H2S production provides for long-term oxygen sensing. In: Acta Physiologica. 2019.
@article{cd9238626b4b47679de7daccb15e5403,
title = "Extended hypoxia-mediated H2S production provides for long-term oxygen sensing",
abstract = "Aim: Numerous studies have shown that H2S serves as an acute oxygen sensor in a variety of cells. We hypothesize that H2S also serves in extended oxygen sensing. Methods: Here, we compare the effects of extended exposure (24-48 hours) to varying O2 tensions on H2S and polysulphide metabolism in human embryonic kidney (HEK 293), human adenocarcinomic alveolar basal epithelial (A549), human colon cancer (HTC116), bovine pulmonary artery smooth muscle, human umbilical-derived mesenchymal stromal (stem) cells and porcine tracheal epithelium (PTE) using sulphur-specific fluorophores and fluorometry or confocal microscopy. Results: All cells continuously produced H2S in 21{\%} O2 and H2S production was increased at lower O2 tensions. Decreasing O2 from 21{\%} to 10{\%}, 5{\%} and 1{\%} O2 progressively increased H2S production in HEK293 cells and this was partially inhibited by a combination of inhibitors of H2S biosynthesis, aminooxyacetate, propargyl glycine and compound 3. Mitochondria appeared to be the source of much of this increase in HEK 293 cells. H2S production in all other cells and PTE increased when O2 was lowered from 21{\%} to 5{\%} except for HTC116 cells where 1{\%} O2 was necessary to increase H2S, presumably reflecting the hypoxic environment in vivo. Polysulphides (H2Sn, where n = 2-7), the key signalling metabolite of H2S also appeared to increase in many cells although this was often masked by high endogenous polysulphide concentrations. Conclusion: These results show that cellular H2S is increased during extended hypoxia and they suggest this is a continuously active O2-sensing mechanism in a variety of cells.",
keywords = "hypoxia, mitochondria, oxygen tension, sulphur metabolism",
author = "Olson, {Kenneth R.} and Yan Gao and DeLeon, {Eric R.} and Markel, {Troy A.} and Natalie Drucker and David Boone and Matt Whiteman and Steiger, {Andrea K.} and Pluth, {Michael D.} and Tessier, {Charles R.} and Stahelin, {Robert V.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1111/apha.13368",
language = "English (US)",
journal = "Acta Physiologica",
issn = "1748-1708",

}

TY - JOUR

T1 - Extended hypoxia-mediated H2S production provides for long-term oxygen sensing

AU - Olson, Kenneth R.

AU - Gao, Yan

AU - DeLeon, Eric R.

AU - Markel, Troy A.

AU - Drucker, Natalie

AU - Boone, David

AU - Whiteman, Matt

AU - Steiger, Andrea K.

AU - Pluth, Michael D.

AU - Tessier, Charles R.

AU - Stahelin, Robert V.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Aim: Numerous studies have shown that H2S serves as an acute oxygen sensor in a variety of cells. We hypothesize that H2S also serves in extended oxygen sensing. Methods: Here, we compare the effects of extended exposure (24-48 hours) to varying O2 tensions on H2S and polysulphide metabolism in human embryonic kidney (HEK 293), human adenocarcinomic alveolar basal epithelial (A549), human colon cancer (HTC116), bovine pulmonary artery smooth muscle, human umbilical-derived mesenchymal stromal (stem) cells and porcine tracheal epithelium (PTE) using sulphur-specific fluorophores and fluorometry or confocal microscopy. Results: All cells continuously produced H2S in 21% O2 and H2S production was increased at lower O2 tensions. Decreasing O2 from 21% to 10%, 5% and 1% O2 progressively increased H2S production in HEK293 cells and this was partially inhibited by a combination of inhibitors of H2S biosynthesis, aminooxyacetate, propargyl glycine and compound 3. Mitochondria appeared to be the source of much of this increase in HEK 293 cells. H2S production in all other cells and PTE increased when O2 was lowered from 21% to 5% except for HTC116 cells where 1% O2 was necessary to increase H2S, presumably reflecting the hypoxic environment in vivo. Polysulphides (H2Sn, where n = 2-7), the key signalling metabolite of H2S also appeared to increase in many cells although this was often masked by high endogenous polysulphide concentrations. Conclusion: These results show that cellular H2S is increased during extended hypoxia and they suggest this is a continuously active O2-sensing mechanism in a variety of cells.

AB - Aim: Numerous studies have shown that H2S serves as an acute oxygen sensor in a variety of cells. We hypothesize that H2S also serves in extended oxygen sensing. Methods: Here, we compare the effects of extended exposure (24-48 hours) to varying O2 tensions on H2S and polysulphide metabolism in human embryonic kidney (HEK 293), human adenocarcinomic alveolar basal epithelial (A549), human colon cancer (HTC116), bovine pulmonary artery smooth muscle, human umbilical-derived mesenchymal stromal (stem) cells and porcine tracheal epithelium (PTE) using sulphur-specific fluorophores and fluorometry or confocal microscopy. Results: All cells continuously produced H2S in 21% O2 and H2S production was increased at lower O2 tensions. Decreasing O2 from 21% to 10%, 5% and 1% O2 progressively increased H2S production in HEK293 cells and this was partially inhibited by a combination of inhibitors of H2S biosynthesis, aminooxyacetate, propargyl glycine and compound 3. Mitochondria appeared to be the source of much of this increase in HEK 293 cells. H2S production in all other cells and PTE increased when O2 was lowered from 21% to 5% except for HTC116 cells where 1% O2 was necessary to increase H2S, presumably reflecting the hypoxic environment in vivo. Polysulphides (H2Sn, where n = 2-7), the key signalling metabolite of H2S also appeared to increase in many cells although this was often masked by high endogenous polysulphide concentrations. Conclusion: These results show that cellular H2S is increased during extended hypoxia and they suggest this is a continuously active O2-sensing mechanism in a variety of cells.

KW - hypoxia

KW - mitochondria

KW - oxygen tension

KW - sulphur metabolism

UR - http://www.scopus.com/inward/record.url?scp=85073990800&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85073990800&partnerID=8YFLogxK

U2 - 10.1111/apha.13368

DO - 10.1111/apha.13368

M3 - Article

C2 - 31442361

AN - SCOPUS:85073990800

JO - Acta Physiologica

JF - Acta Physiologica

SN - 1748-1708

M1 - e13368

ER -