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Oxygen pathway modeling estimates high reactive oxygen species production above the highest permanent human habitation.

Cano I, Selivanov V, Gomez-Cabrero D, Tegnér J, Roca J, Wagner PD, Cascante M - PLoS ONE (2014)

Bottom Line: However, altitude triggers high mitochondrial ROS production in muscle regions with high metabolic capacity but limited O2 delivery.This altitude roughly coincides with the highest location of permanent human habitation.Above 25,000 ft., more than 90% of exercising muscle is predicted to produce abnormally high levels of ROS, corresponding to the "death zone" in mountaineering.

View Article: PubMed Central - PubMed

Affiliation: Center for respiratory diagnoses, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES) and Universitat de Barcelona, Barcelona, Catalonia, Spain.

ABSTRACT
The production of reactive oxygen species (ROS) from the inner mitochondrial membrane is one of many fundamental processes governing the balance between health and disease. It is well known that ROS are necessary signaling molecules in gene expression, yet when expressed at high levels, ROS may cause oxidative stress and cell damage. Both hypoxia and hyperoxia may alter ROS production by changing mitochondrial Po2 (PmO2). Because PmO2 depends on the balance between O2 transport and utilization, we formulated an integrative mathematical model of O2 transport and utilization in skeletal muscle to predict conditions to cause abnormally high ROS generation. Simulations using data from healthy subjects during maximal exercise at sea level reveal little mitochondrial ROS production. However, altitude triggers high mitochondrial ROS production in muscle regions with high metabolic capacity but limited O2 delivery. This altitude roughly coincides with the highest location of permanent human habitation. Above 25,000 ft., more than 90% of exercising muscle is predicted to produce abnormally high levels of ROS, corresponding to the "death zone" in mountaineering.

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Related in: MedlinePlus

Dynamics of ROS production (expressed as SQo produced, normalized to total complex III abundance (taken as 0.4 nmol/mg mitochondrial protein)) at four steady state concentrations of oxygen (expressed as mitochondrial Po2 relative to P50, the oxygen partial pressure at the half-maximal rate of respiration).Before and after exercise, rest is simulated (no ATP hydrolysis, proton gradient dissipates only due to membrane leak). Between 2 and 6.6 min, exercise is simulated (membrane proton gradient dissipates due to ATP hydrolysis and ATP synthase activity). Overall, ROS production falls into two distinct patterns: one (HR, seen when ) reflects high ROS generation and the other (LR, when ) reflects little or no ROS generation compared to rest. Note post-exercise persistence of high ROS generation, especially at the lowest  to P50 ratio.
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pone-0111068-g001: Dynamics of ROS production (expressed as SQo produced, normalized to total complex III abundance (taken as 0.4 nmol/mg mitochondrial protein)) at four steady state concentrations of oxygen (expressed as mitochondrial Po2 relative to P50, the oxygen partial pressure at the half-maximal rate of respiration).Before and after exercise, rest is simulated (no ATP hydrolysis, proton gradient dissipates only due to membrane leak). Between 2 and 6.6 min, exercise is simulated (membrane proton gradient dissipates due to ATP hydrolysis and ATP synthase activity). Overall, ROS production falls into two distinct patterns: one (HR, seen when ) reflects high ROS generation and the other (LR, when ) reflects little or no ROS generation compared to rest. Note post-exercise persistence of high ROS generation, especially at the lowest to P50 ratio.

Mentions: Overall, the mitochondrial ROS generation model produces two distinct patterns of response to at maximum exercise, as displayed in Figure 1. One pattern (HR) reflects above normal high ROS generation and the other (LR) reflects little or normal ROS generation. Briefly, the figure shows the rate of mitochondrial ROS production expressed as concentration of semiquinone radicals (nmol/mg) at Qo site (ubiquinone binding site to complex III at the outer side of the inner mitochondrial membrane) of mitochondrial complex III (y-axis) against time (x-axis) for four different values of , indicated in Figure 1.


Oxygen pathway modeling estimates high reactive oxygen species production above the highest permanent human habitation.

Cano I, Selivanov V, Gomez-Cabrero D, Tegnér J, Roca J, Wagner PD, Cascante M - PLoS ONE (2014)

Dynamics of ROS production (expressed as SQo produced, normalized to total complex III abundance (taken as 0.4 nmol/mg mitochondrial protein)) at four steady state concentrations of oxygen (expressed as mitochondrial Po2 relative to P50, the oxygen partial pressure at the half-maximal rate of respiration).Before and after exercise, rest is simulated (no ATP hydrolysis, proton gradient dissipates only due to membrane leak). Between 2 and 6.6 min, exercise is simulated (membrane proton gradient dissipates due to ATP hydrolysis and ATP synthase activity). Overall, ROS production falls into two distinct patterns: one (HR, seen when ) reflects high ROS generation and the other (LR, when ) reflects little or no ROS generation compared to rest. Note post-exercise persistence of high ROS generation, especially at the lowest  to P50 ratio.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4222897&req=5

pone-0111068-g001: Dynamics of ROS production (expressed as SQo produced, normalized to total complex III abundance (taken as 0.4 nmol/mg mitochondrial protein)) at four steady state concentrations of oxygen (expressed as mitochondrial Po2 relative to P50, the oxygen partial pressure at the half-maximal rate of respiration).Before and after exercise, rest is simulated (no ATP hydrolysis, proton gradient dissipates only due to membrane leak). Between 2 and 6.6 min, exercise is simulated (membrane proton gradient dissipates due to ATP hydrolysis and ATP synthase activity). Overall, ROS production falls into two distinct patterns: one (HR, seen when ) reflects high ROS generation and the other (LR, when ) reflects little or no ROS generation compared to rest. Note post-exercise persistence of high ROS generation, especially at the lowest to P50 ratio.
Mentions: Overall, the mitochondrial ROS generation model produces two distinct patterns of response to at maximum exercise, as displayed in Figure 1. One pattern (HR) reflects above normal high ROS generation and the other (LR) reflects little or normal ROS generation. Briefly, the figure shows the rate of mitochondrial ROS production expressed as concentration of semiquinone radicals (nmol/mg) at Qo site (ubiquinone binding site to complex III at the outer side of the inner mitochondrial membrane) of mitochondrial complex III (y-axis) against time (x-axis) for four different values of , indicated in Figure 1.

Bottom Line: However, altitude triggers high mitochondrial ROS production in muscle regions with high metabolic capacity but limited O2 delivery.This altitude roughly coincides with the highest location of permanent human habitation.Above 25,000 ft., more than 90% of exercising muscle is predicted to produce abnormally high levels of ROS, corresponding to the "death zone" in mountaineering.

View Article: PubMed Central - PubMed

Affiliation: Center for respiratory diagnoses, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES) and Universitat de Barcelona, Barcelona, Catalonia, Spain.

ABSTRACT
The production of reactive oxygen species (ROS) from the inner mitochondrial membrane is one of many fundamental processes governing the balance between health and disease. It is well known that ROS are necessary signaling molecules in gene expression, yet when expressed at high levels, ROS may cause oxidative stress and cell damage. Both hypoxia and hyperoxia may alter ROS production by changing mitochondrial Po2 (PmO2). Because PmO2 depends on the balance between O2 transport and utilization, we formulated an integrative mathematical model of O2 transport and utilization in skeletal muscle to predict conditions to cause abnormally high ROS generation. Simulations using data from healthy subjects during maximal exercise at sea level reveal little mitochondrial ROS production. However, altitude triggers high mitochondrial ROS production in muscle regions with high metabolic capacity but limited O2 delivery. This altitude roughly coincides with the highest location of permanent human habitation. Above 25,000 ft., more than 90% of exercising muscle is predicted to produce abnormally high levels of ROS, corresponding to the "death zone" in mountaineering.

Show MeSH
Related in: MedlinePlus