Effect of oxygen tension on cellular energetics

Wilson, David F.; Erecińska, Maria; Drown, C.; Silver, Ian A.

doi:10.1152/ajpcell.1977.233.5.c135

Cited by 195 publications

(142 citation statements)

References 20 publications

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“…Therefore, the original expression for / OxPhos proposed by Vicini and Kushmerick 62 was modified in the present model by including an oxygen dependency, which is important at higher exercise intensities where oxygen could be very low and affect metabolism. [67][68][69] During exercise, oxygen dependency affects the dynamics of muscle oxygen utilization, but does not affect muscle oxygen uptake s j VO 2m because the venous oxygen concentration dynamics is not greatly affected. It is worth noticing that, in our model, we assume the rate of ATP production associated with oxidative phosphorylation to be six times the rate of oxygen consumption (i.e., b = 6).…”

Section: Linking Simulated and Measured Fluxesmentioning

confidence: 99%

“…53 The model equations account for cellular ATPase, oxidative phosphorylation and CK fluxes variations in skeletal muscle during exercise, where the cellular respiration is regulated by feedback control with dependence from ADP and oxygen concentrations. [13][14][15][67][68][69] It is worth to note that, in the literature, several feedback and feed forward control models have been proposed to describe the regulation of cellular respiration in vivo, such as (1) feedback control using a Michaelis-Menten relationship between oxidative phosphorylation and [ADP], (2) higher-order feedback control using an expression in which the Hill coefficient is greater than 1, or (3) a more fundamental expression of relating oxidative phosphorylation to the free energy of ATP hydrolysis. 34,41,63 Furthermore, some other scientists have proposed feed forward mechanisms to control oxidative phosphorylation.…”

Section: Linking Simulated and Measured Fluxesmentioning

confidence: 99%

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Linking Pulmonary Oxygen Uptake, Muscle Oxygen Utilization and Cellular Metabolism during Exercise

et al. 2007

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Abstract-The energy demand imposed by physical exercise on the components of the oxygen transport and utilization system requires a close link between cellular and external respiration in order to maintain ATP homeostasis. Invasive and non-invasive experimental approaches have been used to elucidate mechanisms regulating the balance between oxygen supply and consumption during exercise. Such approaches suggest that the mechanism controlling the various subsystems coupling internal to external respiration are part of a highly redundant and hierarchical multi-scale system. In this work, we present a ''systems biology'' framework that integrates experimental and theoretical approaches able to provide simultaneously reliable information on the oxygen transport and utilization processes occurring at the various steps in the pathway of oxygen from air to mitochondria, particularly at the onset of exercise. This multi-disciplinary framework provides insights into the relationship between cellular oxygen consumption derived from measurements of muscle oxygenation during exercise and pulmonary oxygen uptake by indirect calorimetry. With a validated model, muscle oxygen dynamic responses is simulated and quantitatively related to cellular metabolism under a variety of conditions.

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Section: Linking Simulated and Measured Fluxesmentioning

confidence: 99%

Section: Linking Simulated and Measured Fluxesmentioning

confidence: 99%

Linking Pulmonary Oxygen Uptake, Muscle Oxygen Utilization and Cellular Metabolism during Exercise

et al. 2007

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“…In tissues having a high fermentative capacity such as maize root tips, it would be difficult, at low PO2 and in the absence of NaF, to discriminate between the part played by the 02-controlled respiration and that played by the fermentation controlled by sugars, in the variation of nucleotide ratios. Such a situation is well illustrated in mammalian kidney cells (20). Under these conditions, there is a good correspondence between the values of the ATP/ADP ratio and the respiratory rate which started to decline at the same pO2 as ATP/ADP or even slightly before.…”

Section: Discussionmentioning

confidence: 58%

“…However, from data obtained with germinating lettuce seeds (14) or animal cells (20), it seems reasonable to assume that this correlation could be quite universal. The value reached by ATP/ADP when the pO2 limited the respiratory rate was not a transient drop, the ratio remained stable at a given pO2…”

Section: Discussionmentioning

confidence: 99%

Oxygen Transport and Root Respiration of Maize Seedlings

Saglio¹,

Raymond²,

Pradet³

1983

Plant Physiol.

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Oxygen uptake and ATP/ADP ratio were simultaneously monitored during incubation of excised maize (Zea mays L. INRA 508) root tips under varying 02 partial pressure. Both variables were independent of 02 tension until a critical 02 pressure was reached. Below this pressure, ATP/ ADP ratio and respiratory rate declined. However, in tissues having a high glycolytic capacity, the correlation between the ATP/ADP ratio and the respiratory rate breaks down as 02 tension decreases, due to the increasing contribution of fermentative processes.In presence of 2 millimolar NaF, the ATP/ADP ratio varied solely as a function of the 02 tension, without interference by fermentative activity, and a close correlation links the ATP/ADP ratio and the respiratory rate of excised maize root tips over the whole range of 02 tensions tested.Using this correlation, a method is proposed for the quantitative determination of the relative cellular respiratory rate permitted by 02 transport from the aerial part of young maize seedlings along the seminal root placed in an anoxic environment.Data are presented which demonstrate the preeminent part played by the cortical air spaces in 02 transport. Their contribution to respiration was high in the first few centimeters nearest the seed and decreased rapidly as the distance from the aerated source increased. It is concluded that 02 transport might contribute to the survival or to adaptive responses of root tissues in flooded soils but that the ventilation of the apical growing zone was inadequate to sustain the growth.penetrating significantly into the cells. Its principal favorable effect would not be so much to feed the respiration but to detoxify the surrounding medium by oxidizing the reduced ions. Using the Oz-dependent chemiluminescence of plant tissues (18) The debate on the actual significance of 02 transport for root metabolism arises because the methods used do not quantify the amount of 02 actually used in the respiration of tissues along the root in situ.In earlier papers, it has been shown that the value of the ATP/ ADP ratio or of the energy charge in lettuce seeds (11,14) was controlled by the pO21. A method has been proposed, which uses the energy charge value as an indirect assessment ofthe respiration permitted by the internal 02 transport in tips of intact rice and maize roots placed in an anaerobic environment (13). This method has been used to demonstrate the efficiency of the internal ventilation in bulrush (17). This paper is a refinement of this approach. It shows that in the presence of fluoride a close correlation links the ATP/ADP ratio and the respiratory rate controlled by the pO2 in maize root tips. This correlation is used to demonstrate an 02 transport and to quantify its involvement in the respiratory metabolism along the seminal root of young maize seedlings.It is now widely accepted that O2 can move through the gas spaces of plant tissues (for review, see 19). Some water plants, such as yellow water lily (2), have developed anatomical devices very effi...

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“…Hypoxic tumour cells have increased cellular NADH/NAD ratios, which can reduce available NAD levels at least three-fold (Wilson et al, 1977). In addition, NADH will act as a potent inhibitor of PADPRP (Ueda et al, 1982) with a Kj value of 5 JM (in the same range as 3-aminobenzamide, Kj 1.8 gM, Purnell and Whish, 1980).…”

Section: Discussionmentioning

confidence: 99%

Low nicotinamide mononucleotide adenylyltransferase activity in a tiazofurin-resistant cell line: effects on NAD metabolism and DNA repair

Boulton

Kyle²,

Durkacz³

1997

Br J Cancer

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Summary Poly(ADP-ribose) polymerase (PADPRP), which uses NAD to synthesize ADP-ribose polymers, is activated by DNA strand breaks and mediates cellular responses to DNA damage. The consequences of low cellular NAD levels in a cell line deficient in nicotinamide mononucleotide adenylyltransferase (NMNAT), an enzyme essential for NAD biosynthesis, were investigated by assessing NAD metabolism and DNA repair after treatment with alkylating agents. A tiazofurin-resistant L1210 cell line (TZR) was isolated. NAD levels were approximately 5933 and 3375 pmol mg-1 protein for parental (wild type, WT) and TZR cells respectively, and NMNAT levels were reduced by > 95%. TZR cells were more sensitive to temozolomide (TM) and 1 -methyl-3-nitro-1 -nitroso-guanidine (MNNG), particularly at concentrations that caused > 50% NAD depletion. TM and MNNG treatment decreased NAD levels in both cell lines, but took longer to return to control levels in TZR cells. For example, MNNG (5 gM), depleted NAD levels at 6 h to approximately 4512 (WT) and 1442 (TZR) pmol mg-1 protein; however, NAD levels had returned to control levels by 8 h in WT cells, but were not restored by 16 h in TZR cells. Both cell lines were equisensitive to the growth-inhibitory effects of NU1025 per se (IC50 370 ,UM). Co-exposure of the cell lines to TM (100 gM) with increasing concentrations of NU1025 led to a synergistic enhancement of cytotoxicity, with IC50 values for NU1025 decreasing to 17 ± 4,gM (TZR) and 37 ± 6 gM (WT). A similar enhanced sensitivity to NU1025 (approximately 2.7-fold) was obtained when TZR cells were co-exposed to MNNG + NU1025. TM-induced DNA strand breaks were increased by co-incubation with NU1025, and again the TZR cell line showed increased sensitivity to NU1025. There were no significant changes in NMNAT activity in response to MNNG treatment over 24 h, either in the presence or in the absence of NU1025. These data demonstrate that modest decreases in cellular NAD levels can sensitize cells to alkylating agents and PADPRP inhibitors.

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Effect of oxygen tension on cellular energetics

Cited by 195 publications

References 20 publications

Linking Pulmonary Oxygen Uptake, Muscle Oxygen Utilization and Cellular Metabolism during Exercise

Linking Pulmonary Oxygen Uptake, Muscle Oxygen Utilization and Cellular Metabolism during Exercise

Oxygen Transport and Root Respiration of Maize Seedlings

Low nicotinamide mononucleotide adenylyltransferase activity in a tiazofurin-resistant cell line: effects on NAD metabolism and DNA repair

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