2020
DOI: 10.3389/fphys.2020.00886
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Adaptive Potential of the Heme Oxygenase/Carbon Monoxide Pathway During Hypoxia

Abstract: Heme oxygenase (HO) enzymes catalyze heme into biliverdin, releasing carbon monoxide (CO) and iron into circulation. These byproducts of heme degradation can have potent cytoprotective effects in the face of stressors such as hypoxia and ischemia-reperfusion events. The potential for exogenous use of CO as a therapeutic agent has received increasing attention throughout the past few decades. Further, HO and CO are noted as putatively adaptive in diving mammals and certain high-altitude human populations that a… Show more

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Cited by 22 publications
(28 citation statements)
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“…High altitude exposure has been shown to increased exhaled CO levels, and carboxyhemoglobin levels are positively associated with hematocrit in Andean high-altitude residents ( Tift et al, 2020 ). This is suspected to be caused by increased red blood cell turnover, a persistent stress erythropoiesis response, or a unique HO/CO pathway mechanism.…”
Section: Lessons From High-altitude Acclimatized and Adapted Groupsmentioning
confidence: 99%
“…High altitude exposure has been shown to increased exhaled CO levels, and carboxyhemoglobin levels are positively associated with hematocrit in Andean high-altitude residents ( Tift et al, 2020 ). This is suspected to be caused by increased red blood cell turnover, a persistent stress erythropoiesis response, or a unique HO/CO pathway mechanism.…”
Section: Lessons From High-altitude Acclimatized and Adapted Groupsmentioning
confidence: 99%
“…Considering that NES routinely dive for over an hour and spend very little time at the surface recovering from these long duration dives, suggesting minimal production of anaerobic metabolic byproducts during dives that must be dealt with at the surface (Thorson and Le Boeuf, 1994;Hassrick et al, 2010), we do not believe their onboard CO concentrations limit adequate oxygen delivery. Instead, we believe the high quantities of intravascular and extravascular CO seen in this species likely plays a cytoprotective role to resist injuries to tissues that routinely experience hypoxia and ischemia and reperfusion events (Tift et al, 2020). We found that baseline gene expression in skeletal muscle was highly correlated by function, including (1) protection from lipid peroxidation (mRC1), (2) mitochondrial biogenesis (mRC2), (3) CO production (mRC3), and (4) regulation of inflammation (mRC4), all of which were associated with concentrations of CO in skeletal muscle.…”
Section: Discussionmentioning
confidence: 92%
“…However, the role and regulation of endogenous CO production and its potential to exert similar effects in species that are naturally adapted to chronic hypoxia have not been studied. One of the deepest-diving marine mammals, NES, produce and maintain CO at concentrations higher than those of cigarette smokers, and avoid tissue injuries typically seen in other mammals that experience repeated exposure to hypoxemia and ischemia-reperfusion events (Tift et al, 2014(Tift et al, , 2020. Due to the large amount of evidence demonstrating the cytoprotective FIGURE 4 | Boxplots showing expression of rotated components mRC1 (A; GPX4, PRDX6, PRDX1, SIRT1), mRC2 (B; PGC1A, ESRRA, ESRRG), mRC3 (C; HMOX1, BVR, GPX3, PRDX1), and mRC4 (D; HMOX2, NRF2, IL1B) in skeletal muscle of NES.…”
Section: Discussionmentioning
confidence: 99%
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