Hypoxia induces a time- and tissue-specific response that elicits intertissue circadian clock misalignment

The occurrence and sequelae of disorders that lead to hypoxic spells such as asthma, chronic obstructive pulmonary disease, and obstructive sleep apnea (OSA) exhibit daily variance. This prompted us to examine the interaction between the hypoxic response and the circadian clock in vivo. We found tha...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2020-01, Vol.117 (1), p.779-786
Main Authors: Manella, Gal, Aviram, Rona, Bolshette, Nityanand, Muvkadi, Sapir, Golik, Marina, Smith, David F., Asher, Gad
Format: Article
Language:English
Subjects:
Animals
Apnea
Asthma
Biological clocks
Biological Sciences
Chronic obstructive pulmonary disease
Circadian Clocks - physiology
Circadian rhythm
Circadian rhythms
Complications
Disease Models, Animal
Gene Expression Regulation - physiology
Humans
Hypoxia
Hypoxia - etiology
Hypoxia - physiopathology
Kidney - metabolism
Liver - metabolism
Lung - metabolism
Lung diseases
Male
Mice
Misalignment
Obstructive lung disease
Oxygen - metabolism
Phase coherence
Photoperiod
Post-transcription
RNA-Seq
Sleep
Sleep apnea
Sleep Apnea, Obstructive - etiology
Sleep Apnea, Obstructive - physiopathology
Sleep disorders
Time dependence
Time of use
Tissues
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Summary:The occurrence and sequelae of disorders that lead to hypoxic spells such as asthma, chronic obstructive pulmonary disease, and obstructive sleep apnea (OSA) exhibit daily variance. This prompted us to examine the interaction between the hypoxic response and the circadian clock in vivo. We found that the global transcriptional response to acute hypoxia is tissue-specific and time-of-day–dependent. In particular, clock components differentially responded at the transcriptional and posttranscriptional level, and these responses depended on an intact circadian clock. Importantly, exposure to hypoxia phase-shifted clocks in a tissue-dependent manner led to intertissue circadian clock misalignment. This differential response relied on the intrinsic properties of each tissue and could be recapitulated ex vivo. Notably, circadian misalignment was also elicited by intermittent hypoxia, a widely used model for OSA. Given that phase coherence between circadian clocks is considered favorable, we propose that hypoxia leads to circadian misalignment, contributing to the pathophysiology of OSA and potentially other diseases that involve hypoxia.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1914112117