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Hydrogen Sulfide as an Oxygen Sensor

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Hydrogen Sulfide and its Therapeutic Applications

Abstract

Eukaryotic cells depend upon oxygen (O2) for their survival and elaborate mechanisms have evolved in multicellular animals, especially vertebrates, to monitor the availability of environmental O2, the efficiency of O2 extraction from the environment, ensure adequate O2 delivery to tissues and even to regulate cellular metabolism when O2 availability is compromised. In vertebrates, specialized O2 “sensing” cells have developed to carry out many of these processes. Although all O2 sensing cells ultimately couple low Po 2 (hypoxia) to physiological responses, how these cells actually detect hypoxia, i.e., the “O2 sensor” remains controversial. We have recently proposed that hydrogen sulfide (H2S) through its O2-dependent metabolism is a universal and phylogenetically ancient O2 sensing mechanism. This hypothesis is based on a variety of experimental evidence including; (1) the effects of exogenous H2S mimic hypoxia, (2) H2S production and/or metabolism is biochemically coupled to O2, (3) tissue H2S concentration is inversely related to Po 2 at physiologically relevant Po 2s, (4) compounds that inhibit or augment H2S production inhibit and augment hypoxic responses, (5) H2S acts upon effector mechanisms known to mediate hypoxic responses, (6) H2S was key to the origin of life and the advent of eukaryotic cells and the reciprocal relationship between O2 and H2S has been inexorably intertwined throughout evolution. The evidence for H2S-mediated O2 sensing is critically examined in this review.

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Abbreviations

3MP:

3-Mercaptopyruvate

3-MST:

3-Mercaptopyruvate sulfur transferase

AMPK:

AMP-activated protein kinase

AOA:

Amino-oxyacetate

AOX:

Alternative oxidase

Asp:

Aspartic acid

CAT:

Cysteine aminotransferase

CBS:

Cystathionine β-synthase

CDO:

Cysteine dioxygenase

CO:

Carbon monoxide

CSE:

Cystathionine γ-lyase

Cys:

Cysteine

DAO:

d-amino acid oxidase

DHLA:

Dihydrolipoic acid

EC50 :

Effective concentration for half-maximal activity

ETHE1:

Mitochondrial sulfur dioxygenase

Gly:

Glycine

GSH:

Reduced glutathione

GSSG:

Oxidized glutathione

H2O2 :

Hydrogen peroxide

H2S:

Hydrogen sulfide

HA:

Hydroxylamine

HIF:

Hypoxia-inducible factor

HPC:

Hypoxic pulmonary vasoconstriction

HSD:

Hypoxic systemic vasodilation

IKCa :

Intermediate conductance potassium channel

KATP :

Adenosine triphosphate sensitive potassium channel

KCl:

Potassium chloride

Ki :

Inhibition constant

Kv :

Voltage-gated potassium channels

NEB:

Neuroepithelial bodies

NEC:

Neuroepithelial cells

NO:

Nitric oxide

O2 − :

Superoxide

PASMC:

Pulmonary artery smooth muscle cells

pB:

Pre-Bötzinger respiratory group

PKCε:

Protein kinase C epsilon

PLP:

Pyridoxal 5′phosphate

Po 2 :

Partial pressure of oxygen

PPG:

Propargyl glycine

Rde:

Rhodanase

RI:

Ischemia reperfusion injury

ROS:

Reactive oxygen species

R-SO:

Sulfenyl

S2O3 2− :

Thiosulfate

SO:

Sulfur oxidase

SO3 2− :

Sulfite

SO4 2− :

Sulfate

SQR:

Sulfide:quinone oxidoreductase

ST:

Sulfur transferase

TASK:

Acid-sensitive potassium channel

TR:

Thiosulfate reductase, a.k.a. rhodanase

TRD:

Thioredoxin reductase

Trx:

Thioredoxin

α-Kg:

α-ketoglutarate

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Acknowledgments

The author wishes to acknowledge the numerous colleagues that contributed to this research. The author’s work has been supported by National Science Foundation Grants, IBN 0235223, IOS 0641436 and IOS 1051627.

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  1. Indiana University School of Medicine - South Bend, 1234 Notre Dame Avenue, South Bend, IN, 46617, USA

    Kenneth R. Olson

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  1. National Institut of Neuroscience, Tokyo, Japan

    Hideo Kimura

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Olson, K.R. (2013). Hydrogen Sulfide as an Oxygen Sensor. In: Kimura, H. (eds) Hydrogen Sulfide and its Therapeutic Applications. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1550-3_2

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