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

Carreau A, El Hafny-Rahbi B, Matejuk A, Grillon C, Kieda C - J. Cell. Mol. Med. (2011)

Bottom Line: The oxygen partial pressure (pO(2)), which is a key component of the physiological state of an organ, results from the balance between oxygen delivery and its consumption.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 is important to realize that most of the experiments performed in so-called normoxia might be dangerously misleading.

View Article: PubMed Central - PubMed

Affiliation: Centre de Biophysique Moléculaire, CNRS UPR, Orléans, France.

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Related in: MedlinePlus

Nitroimidazole derivatives used as hypoxia markers. (A) Schematic of the proposed mechanism underlying the binding of pimonidazole to cellular macromolecules, as an example of nitroimidazole tracer. (B) Hypoxic sites detection in B16-melanoma induced tumour by pimonidazole binding, visualized in red. More cells are proliferating [4′,6′-diamidino-2-phenylindole (DAPI)-labelled cells in blue] close to the blood vessel. Endothelial cells lining the blood vessel wall are stained in green after incubation with a fluorescent antibody specific for PECAM-1 (CD31).
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fig01: Nitroimidazole derivatives used as hypoxia markers. (A) Schematic of the proposed mechanism underlying the binding of pimonidazole to cellular macromolecules, as an example of nitroimidazole tracer. (B) Hypoxic sites detection in B16-melanoma induced tumour by pimonidazole binding, visualized in red. More cells are proliferating [4′,6′-diamidino-2-phenylindole (DAPI)-labelled cells in blue] close to the blood vessel. Endothelial cells lining the blood vessel wall are stained in green after incubation with a fluorescent antibody specific for PECAM-1 (CD31).

Mentions: In the development of imaging probes for tumour hypoxia, nitroimidazoles have received particular attention as hypoxia markers because of their unique behaviour in hypoxic environments. 2-nitroimidazole (azomycin) was originally found to be an antibiotic against anaerobic bacteria and protozoa in 1953 [2]. Nitroaromatics are selectively reduced by nitroreductase enzymes under hypoxic conditions to form hydroxylamine intermediates that can bind irreversibly to cellular nucleophilic groups in proteins or DNA. This property permits their antibacterial action. The irreversible retention of nitroimidazoles in the cells is also a prerequisite to differentiate between normoxic and hypoxic tissues [3] (Fig. 1A).


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

Carreau A, El Hafny-Rahbi B, Matejuk A, Grillon C, Kieda C - J. Cell. Mol. Med. (2011)

Nitroimidazole derivatives used as hypoxia markers. (A) Schematic of the proposed mechanism underlying the binding of pimonidazole to cellular macromolecules, as an example of nitroimidazole tracer. (B) Hypoxic sites detection in B16-melanoma induced tumour by pimonidazole binding, visualized in red. More cells are proliferating [4′,6′-diamidino-2-phenylindole (DAPI)-labelled cells in blue] close to the blood vessel. Endothelial cells lining the blood vessel wall are stained in green after incubation with a fluorescent antibody specific for PECAM-1 (CD31).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4373326&req=5

fig01: Nitroimidazole derivatives used as hypoxia markers. (A) Schematic of the proposed mechanism underlying the binding of pimonidazole to cellular macromolecules, as an example of nitroimidazole tracer. (B) Hypoxic sites detection in B16-melanoma induced tumour by pimonidazole binding, visualized in red. More cells are proliferating [4′,6′-diamidino-2-phenylindole (DAPI)-labelled cells in blue] close to the blood vessel. Endothelial cells lining the blood vessel wall are stained in green after incubation with a fluorescent antibody specific for PECAM-1 (CD31).
Mentions: In the development of imaging probes for tumour hypoxia, nitroimidazoles have received particular attention as hypoxia markers because of their unique behaviour in hypoxic environments. 2-nitroimidazole (azomycin) was originally found to be an antibiotic against anaerobic bacteria and protozoa in 1953 [2]. Nitroaromatics are selectively reduced by nitroreductase enzymes under hypoxic conditions to form hydroxylamine intermediates that can bind irreversibly to cellular nucleophilic groups in proteins or DNA. This property permits their antibacterial action. The irreversible retention of nitroimidazoles in the cells is also a prerequisite to differentiate between normoxic and hypoxic tissues [3] (Fig. 1A).

Bottom Line: The oxygen partial pressure (pO(2)), which is a key component of the physiological state of an organ, results from the balance between oxygen delivery and its consumption.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 is important to realize that most of the experiments performed in so-called normoxia might be dangerously misleading.

View Article: PubMed Central - PubMed

Affiliation: Centre de Biophysique Moléculaire, CNRS UPR, Orléans, France.

Show MeSH
Related in: MedlinePlus