Intracellular PO2 of the Carotid Body

Wilson, David F.; Evans, Sydney M.; Rozanov, Charmaine; Roy, Arijit; Koch, Cameron J.; Laughlin, Kristine M.; Lahiri, S.

doi:10.1007/0-306-46825-5_62

Cited by 5 publications

(5 citation statements)

References 25 publications

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“…The CB has been extensively studied with its Po 2 profile, and intact CB microvascular Po 2 ranges from 50-55 Torr (Lahiri et al 1993) and intracellular Po 2 at 30-35 Torr (Wilson et al 2000). Thus, a weak expression of HIF-1a in the CB glomus cells in Nx possibly suggests that lower Po 2 in the CB induces HIF-1a stabilization.…”

Section: Discussionmentioning

confidence: 97%

“…Therefore, the presence of HIF-1a protein observed in the intact CB and glomus cells in Nx corroborates these previous reports. Furthermore, the intracellular Po 2 in normal CB ranges from 30 to 35 Torr (Rumsey et al 1991;Wilson et al 2000), which can also activate expression of HIF-1a protein in the normoxic CB High-power (40) view of glomus cell clusters in C showing strong immunoreactivity of HIF-1a in the nucleus suggesting stabilization and/or induction of HIF-1a in hypoxia (arrows). Note that the cytoplasm of the type-I cells shows immunoreactive granules (large arrows).…”

Section: Hif-1a In Normoxic Cbmentioning

confidence: 97%

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Effects of hypoxia and intracellular iron chelation on hypoxia-inducible factor-1? and -1? in the rat carotid body and glomus cells

Baby

Roy

Mokashi

et al. 2003

Histochemistry and Cell Biology

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The present investigation provides for the first time, unambiguous information on the occurrence of hypoxia-inducible factors (HIF-1alpha and HIF-1beta proteins) in normoxia (Nx) and their interaction with hypoxia (Hx) and intracellular Fe(2+) chelation in the rat carotid body (CB) glomus cells. HIF-1alpha bound to HIF-1beta translocated into the nucleus is identified on the basis of immunohistochemistry and immunofluorescence. In Nx, a weak expression of HIF-1alpha was observed in CB glomus cells. However, exposure of CB and glomus cells to Hx (Po(2) approximately 7 Torr) and Nx with ciclopirox olamine (CPX, 5 microM) for 1 h showed a significant ( P<0.001) increase in HIF-1alpha protein. The CBs and glomus cells exposed to Nx, Hx, and Nx with CPX showed a constant level of HIF-1beta protein expression. HIF-1alpha subunit is continuously synthesized and degraded under normoxic conditions, while it accumulates rapidly following exposure to low oxygen tensions. Hydroxylation of HIF-1alpha by prolyl hydroxylase for proteasomal degradation was dependent on iron, 2-oxoglutarate, and oxygen concentration. The intracellular iron that acts as a cofactor for prolyl hydroxylase activity belongs to the labile iron pool and can be easily chelated. Thus, chelation of intracellular labile iron by CPX in Nx significantly increased HIF-1alpha in CB glomus cells. Thus, the results are consistent with the hypothesis that HIF-1alpha which is present in the glomus cells translocates to the nucleus during exposure to Hx and to CPX in Nx.

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Section: Discussionmentioning

confidence: 97%

Section: Hif-1a In Normoxic Cbmentioning

confidence: 97%

Effects of hypoxia and intracellular iron chelation on hypoxia-inducible factor-1? and -1? in the rat carotid body and glomus cells

Baby

Roy

Mokashi

et al. 2003

Histochemistry and Cell Biology

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“…The use of a calibrated fluorescence scale and a measure of the maximum possible binding of each tumor (cube reference binding) allowed a pixel-by-pixel analysis of the observed EF5 binding as a percentage of cube reference binding. Thus, the endpoints for EF5 binding presented herein reflect both the level and the area of binding (18,26,29). Data were summarized by providing a cumulative frequency (CF) analysis of all pixels.…”

Section: Assessment Of Ef5mentioning

confidence: 99%

“…Tissues obtained at biopsy are either frozen for immunohistochemical analyses or dissociated for flow cytometric analysis of binding (21,24,25). The quantitative methodology involved in the analysis of EF5 binding in human tissue allows the translation of this binding into tissue oxygen levels, and oxygen maps have been generated (17,18,26,27). In a recent publication examining human brain tumor specimens, we showed that the level of EF5 binding corresponds to a semiquantitative measure of the extent of necrosis, as reviewed by a pathologist.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia Is Important in the Biology and Aggression of Human Glial Brain Tumors

Evans

Judy²,

Dunphy

et al. 2004

Clinical Cancer Research

307

237

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“…The maximum binding rate is referred to as CRB and is described below (Koch, 2001;Evans et al, 2004a). Thus, the end points for EF5 binding presented herein reflects both the level and proportional area of binding (Laughlin et al, 1996;Wilson et al, 2000;Evans et al, 2004a).…”

Section: Ef5 Studiesmentioning

confidence: 99%

Oxygen Levels in Normal and Previously Irradiated Human Skin as Assessed by EF5 Binding

Evans

Schrlau

Chalian

et al. 2006

Journal of Investigative Dermatology

114

106

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The oxygen status of skin is a controversial topic. Skin is radiosensitive, suggesting it is well-oxygenated. However, it can be further sensitized with nitroimidazole drugs, implying that it is partially hypoxic. Skin oxygen levels are difficult to measure with either electrodes or the hypoxia-monitoring agent (3)H-misonidazole. For the latter, binding has previously been reported to be high in murine skin, but this could be attributed to either non-oxygen-dependent variations in nitroreductase activity, drug metabolism, and/or actual oxygen gradients. We obtained tumor and skin from patients given EF5, a 2-nitroimidazole tissue hypoxia monitor. We performed immunohistochemical studies using highly specific monoclonal antibodies for the hypoxia-dependent production of EF5 tissue adducts. Some tissue sections were counterstained using either Ki67 for proliferation or CD31 for vessels. We found that the human dermis is well-oxygenated, the epidermis is modestly hypoxic and portions of some sebaceous glands and hair follicles are moderately to severely hypoxic. Normal and irradiated skin had similar oxygenation patterns. Control studies demonstrated that these observations are not due to tissue variations in nitroreductase activity. The importance of the highly heterogeneous distribution of oxygen in skin requires further study, but recent investigations suggest that skin hypoxia may have important clinical ramifications including mediating cellular transformation.

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Intracellular PO2 of the Carotid Body

Cited by 5 publications

References 25 publications

Effects of hypoxia and intracellular iron chelation on hypoxia-inducible factor-1? and -1? in the rat carotid body and glomus cells

Effects of hypoxia and intracellular iron chelation on hypoxia-inducible factor-1? and -1? in the rat carotid body and glomus cells

Hypoxia Is Important in the Biology and Aggression of Human Glial Brain Tumors

Oxygen Levels in Normal and Previously Irradiated Human Skin as Assessed by EF5 Binding

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