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Reactive oxygen radicals and gaseous transmitters in carotid body activation by intermittent hypoxia.
Cell Tissue Res. 2018 05; 372(2):427-431.CT

Abstract

Sleep apnea is a prevalent respiratory disease characterized by periodic cessation of breathing during sleep causing intermittent hypoxia (IH). Sleep apnea patients and rodents exposed to IH exhibit elevated sympathetic nerve activity and hypertension. A heightened carotid body (CB) chemoreflex has been implicated in causing autonomic abnormalities in IH-treated rodents and in sleep apnea patients. The purpose of this article is to review the emerging evidence showing that interactions between reactive oxygen species (ROS) and gaseous transmitters as a mechanism cause hyperactive CB by IH. Rodents treated with IH exhibit markedly elevated ROS in the CB, which is due to transcriptional upregulation of pro-oxidant enzymes by hypoxia-inducible factor (HIF)-1 and insufficient transcriptional regulation of anti-oxidant enzymes by HIF-2. ROS, in turn, increases cystathionine γ-lyase (CSE)-dependent H2S production in the CB. Blockade of H2S synthesis prevents IH-evoked CB activation. However, the effects of ROS on H2S production are not due to direct effects on CSE enzyme activity but rather due to inactivation of heme oxygenase-2 (HO-2), a carbon monoxide (CO) producing enzyme. CO inhibits H2S production through inactivation of CSE by PKG-dependent phosphorylation. During IH, reduced CO production resulting from inactivation of HO-2 by ROS releases the inhibition of CO on CSE thereby increasing H2S. Inhibiting H2S synthesis prevented IH-evoked sympathetic activation and hypertension.

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Authors+Show Affiliations

Prabhakar NR
Institute for Integrative Physiology and Center for Systems Biology of O2 Sensing, Biological Sciences Division, University of Chicago, MC 5068, 5841 South Maryland Avenue, Chicago, IL, 60637, USA. nanduri@uchicago.edu.
Peng YJ
Institute for Integrative Physiology and Center for Systems Biology of O2 Sensing, Biological Sciences Division, University of Chicago, MC 5068, 5841 South Maryland Avenue, Chicago, IL, 60637, USA.
Yuan G
Institute for Integrative Physiology and Center for Systems Biology of O2 Sensing, Biological Sciences Division, University of Chicago, MC 5068, 5841 South Maryland Avenue, Chicago, IL, 60637, USA.
Nanduri J
Institute for Integrative Physiology and Center for Systems Biology of O2 Sensing, Biological Sciences Division, University of Chicago, MC 5068, 5841 South Maryland Avenue, Chicago, IL, 60637, USA.

MeSH

AnimalsCarotid BodyGasesHumansHydrogen SulfideHypoxiaReactive Oxygen Species

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Review

Language

eng

PubMed ID

29470646

Citation

Prabhakar, Nanduri R., et al. "Reactive Oxygen Radicals and Gaseous Transmitters in Carotid Body Activation By Intermittent Hypoxia." Cell and Tissue Research, vol. 372, no. 2, 2018, pp. 427-431.
Prabhakar NR, Peng YJ, Yuan G, et al. Reactive oxygen radicals and gaseous transmitters in carotid body activation by intermittent hypoxia. Cell Tissue Res. 2018;372(2):427-431.
Prabhakar, N. R., Peng, Y. J., Yuan, G., & Nanduri, J. (2018). Reactive oxygen radicals and gaseous transmitters in carotid body activation by intermittent hypoxia. Cell and Tissue Research, 372(2), 427-431. https://doi.org/10.1007/s00441-018-2807-0
Prabhakar NR, et al. Reactive Oxygen Radicals and Gaseous Transmitters in Carotid Body Activation By Intermittent Hypoxia. Cell Tissue Res. 2018;372(2):427-431. PubMed PMID: 29470646.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reactive oxygen radicals and gaseous transmitters in carotid body activation by intermittent hypoxia. AU - Prabhakar,Nanduri R, AU - Peng,Ying-Jie, AU - Yuan,Guoxiang, AU - Nanduri,Jayasri, Y1 - 2018/02/22/ PY - 2017/12/18/received PY - 2018/01/23/accepted PY - 2018/2/23/pubmed PY - 2019/1/15/medline PY - 2018/2/23/entrez KW - Carbon monoxide KW - Cystathionine γ-lyase KW - Heme oxygenase-2 KW - Hydrogen sulfide KW - Sleep apnea SP - 427 EP - 431 JF - Cell and tissue research JO - Cell Tissue Res VL - 372 IS - 2 N2 - Sleep apnea is a prevalent respiratory disease characterized by periodic cessation of breathing during sleep causing intermittent hypoxia (IH). Sleep apnea patients and rodents exposed to IH exhibit elevated sympathetic nerve activity and hypertension. A heightened carotid body (CB) chemoreflex has been implicated in causing autonomic abnormalities in IH-treated rodents and in sleep apnea patients. The purpose of this article is to review the emerging evidence showing that interactions between reactive oxygen species (ROS) and gaseous transmitters as a mechanism cause hyperactive CB by IH. Rodents treated with IH exhibit markedly elevated ROS in the CB, which is due to transcriptional upregulation of pro-oxidant enzymes by hypoxia-inducible factor (HIF)-1 and insufficient transcriptional regulation of anti-oxidant enzymes by HIF-2. ROS, in turn, increases cystathionine γ-lyase (CSE)-dependent H2S production in the CB. Blockade of H2S synthesis prevents IH-evoked CB activation. However, the effects of ROS on H2S production are not due to direct effects on CSE enzyme activity but rather due to inactivation of heme oxygenase-2 (HO-2), a carbon monoxide (CO) producing enzyme. CO inhibits H2S production through inactivation of CSE by PKG-dependent phosphorylation. During IH, reduced CO production resulting from inactivation of HO-2 by ROS releases the inhibition of CO on CSE thereby increasing H2S. Inhibiting H2S synthesis prevented IH-evoked sympathetic activation and hypertension. SN - 1432-0878 UR - https://www.unboundmedicine.com/medline/citation/29470646/Reactive_oxygen_radicals_and_gaseous_transmitters_in_carotid_body_activation_by_intermittent_hypoxia_ DB - PRIME DP - Unbound Medicine ER -