Renocortical Tissue Oxygen Pressure Measurements in Patients Undergoing Living Donor Kidney Transplantation

Müller, Matthias; Padberg, Winfried; Schindler, Ehrenfried; Sticher, J.; Osmer, Christian; Friemann, S; Hempelmann, G.

doi:10.1097/00000539-199808000-00045

Cited by 17 publications

(13 citation statements)

References 7 publications

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“…In human beings, Müller et al . [66] have reported a study in patients undergoing living donor kidney transplantation. The tissue oxygen pressure was measured in the superficial cortex of the kidney before nephrectomy by using a multiwire tissue surface pO 2 electrode.…”

Section: What Does Physioxia Mean?mentioning

confidence: 99%

Why is the partial oxygen pressure of human tissues a crucial parameter? Small molecules and hypoxia

Carreau

Hafny‐Rahbi

Matejuk

et al. 2011

J Cellular Molecular Medi

1,049

935

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Oxygen supply and diffusion into tissues are necessary for survival. The oxygen partial pressure (pO2), which is a key component of the physiological state of an organ, results from the balance between oxygen delivery and its consumption. In mammals, oxygen is transported by red blood cells circulating in a well-organized vasculature. Oxygen delivery is dependent on the metabolic requirements and functional status of each organ. Consequently, in a physiological condition, organ and tissue are characterized by their own unique ‘tissue normoxia’ or ‘physioxia’ status. Tissue oxygenation is severely disturbed during pathological conditions such as cancer, diabetes, coronary heart disease, stroke, etc., which are associated with decrease in pO2, i.e. ‘hypoxia’. In this review, we present an array of methods currently used for assessing tissue oxygenation. We show that hypoxia is marked during tumour development and has strong consequences for oxygenation and its influence upon chemotherapy efficiency. Then we compare this to physiological pO2 values of human organs. Finally we evaluate consequences of physioxia on cell activity and its molecular modulations. More importantly we emphasize the discrepancy between in vivo and in vitro tissue and cells oxygen status which can have detrimental effects on experimental outcome. It appears that the values corresponding to the physioxia are ranging between 11% and 1% O2 whereas current in vitro experimentations are usually performed in 19.95% O2, an artificial context as far as oxygen balance is concerned. It is important to realize that most of the experiments performed in so-called normoxia might be dangerously misleading.

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Section: What Does Physioxia Mean?mentioning

confidence: 99%

Why is the partial oxygen pressure of human tissues a crucial parameter? Small molecules and hypoxia

Carreau

Hafny‐Rahbi

Matejuk

et al. 2011

J Cellular Molecular Medi

1,049

935

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“…The kidneys comprise only 1% of total body mass, yet filter ~20% of cardiac output kPa in human (411,541). When the measuring electrode is advanced beyond ~3mm (in the rat kidney), a sharp reduction in tissue PO is observed corresponding to entry into the medulla (see Figure 14), where O levels are between kPa in the dog (28), 1.3-4.2 kPa in the rat (50,51,203,334,349,362,519,642), 3.3 kPa in the pig (693) and kPa in human (693).…”

Section: F Kidneysmentioning

confidence: 99%

Defining Physiological Normoxia for Improved Translation of Cell Physiology to Animal Models and Humans

Keeley

Mann

2019

Physiological Reviews

242

204

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The extensive oxygen gradient between the air we breathe (Po2 ~21 kPa) and its ultimate distribution within mitochondria (as low as ~0.5–1 kPa) is testament to the efforts expended in limiting its inherent toxicity. It has long been recognized that cell culture undertaken under room air conditions falls short of replicating this protection in vitro. Despite this, difficulty in accurately determining the appropriate O2 levels in which to culture cells, coupled with a lack of the technology to replicate and maintain a physiological O2 environment in vitro, has hindered addressing this issue thus far. In this review, we aim to address the current understanding of tissue Po2 distribution in vivo and summarize the attempts made to replicate these conditions in vitro. The state-of-the-art techniques employed to accurately determine O2 levels, as well as the issues associated with reproducing physiological O2 levels in vitro, are also critically reviewed. We aim to provide the framework for researchers to undertake cell culture under O2 levels relevant to specific tissues and organs. We envisage that this review will facilitate a paradigm shift, enabling translation of findings under physiological conditions in vitro to disease pathology and the design of novel therapeutics.

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“…In fact, oxygen in arterial blood is only about 12% (1). The oxygen supply to tissues varies from 2-6% in the brain (2), 3-12% in the lungs (3), 3.5-6% in the intestine (4), 4% in the liver (5), 7-12% in the kidney (6), 4% in muscle (7), and 6 -7% in bone marrow (8). A single cell may have as little as 1-2.5% available oxygen (9).…”

Section: From the Department Of Molecular And Cellular Biology Univementioning

confidence: 99%

Human Cells Cultured under Physiological Oxygen Utilize Two Cap-binding Proteins to recruit Distinct mRNAs for Translation

Timpano¹,

Uniacke

2016

Journal of Biological Chemistry

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Translation initiation is a focal point of translational control and requires the binding of eIF4E to the 5 cap of mRNA. Under conditions of extreme oxygen depletion (hypoxia), human cells repress eIF4E and switch to an alternative cap-dependent translation mediated by a homolog of eIF4E, eIF4E2. This homolog forms a complex with the oxygen-regulated hypoxia-inducible factor 2␣ and can escape translation repression. This complex mediates cap-dependent translation under cell culture conditions of 1% oxygen (to mimic tumor microenvironments), whereas eIF4E mediates cap-dependent translation at 21% oxygen (ambient air). However, emerging evidence suggests that culturing cells in ambient air, or "normoxia," is far from physiological or "normal." In fact, oxygen in human tissues ranges from 1-11% or "physioxia." Here we show that two distinct modes of cap-dependent translation initiation are active during physioxia and act on separate pools of mRNAs. The oxygen-dependent activities of eIF4E and eIF4E2 are elucidated by observing their polysome association and the status of mammalian target of rapamycin complex 1 (eIF4E-dependent) or hypoxiainducible factor 2␣ expression (eIF4E2-dependent). We have identified oxygen conditions where eIF4E is the dominant capbinding protein (21% normoxia or standard cell culture conditions), where eIF4E2 is the dominant cap-binding protein (1% hypoxia or ischemic diseases and cancerous tumors), and where both cap-binding proteins act simultaneously to initiate the translation of distinct mRNAs (1-11% physioxia or during development and stem cell differentiation). These data suggest that the physioxic proteome is generated by initiating translation of mRNAs via two distinct but complementary cap-binding proteins.

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Renocortical Tissue Oxygen Pressure Measurements in Patients Undergoing Living Donor Kidney Transplantation

Cited by 17 publications

References 7 publications

Why is the partial oxygen pressure of human tissues a crucial parameter? Small molecules and hypoxia

Why is the partial oxygen pressure of human tissues a crucial parameter? Small molecules and hypoxia

Defining Physiological Normoxia for Improved Translation of Cell Physiology to Animal Models and Humans

Human Cells Cultured under Physiological Oxygen Utilize Two Cap-binding Proteins to recruit Distinct mRNAs for Translation

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