Regulation of EMAP II by hypoxia

Susanne Matschurat, Ulrike E. Knies, Veronika Person, Ludger Fink, Benjamin Stoelcker, Chinedu Ebenebe, Heike A. Behrensdorf, Jutta Schaper, Matthias Clauss

Research output: Contribution to journalArticle

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Abstract

Endothelial-monocyte-activating polypeptide II (EMAP II) is a proinflammatory cytokine and a chemoattractant for monocytes and granulocytes. We have previously shown that EMAP II mRNA is strongly expressed at sites of apoptosis in the mouse embryo and that the mature protein is cleaved from its cellular precursor (proEMAP II/p43) by caspase activation to become released from cells. Here we demonstrate in vivo that EMAP II mRNA expression is strongly increased in tumor necrosis factor α (TNF)-treated murine meth A fibrosarcomas and in B16 melanomas, especially in close proximity to areas of tissue necrosis. Furthermore, by means of confocal microscopy, high level expression of proEMAP II/p43 protein correlated predominantly with hypoxic but also with apoptotic cells. In vitro, EMAP II mRNA levels were not increased by hypoxia. However, high amounts of mature EMAP II protein were detected in the supernatants of hypoxic tumor cells. Unlike in apoptotic cells, neither a broad-range caspase inhibitor nor an inhibitor specific for the internal cleavage site was able to inhibit processing of proEMAP II/p43 to the mature EMAP II protein. In conclusion, these data suggest that hypoxia and apoptosis provide two alternative mechanisms of EMAP II generation by tumor cells.

Original languageEnglish (US)
Pages (from-to)93-103
Number of pages11
JournalAmerican Journal of Pathology
Volume162
Issue number1
StatePublished - Jan 1 2003
Externally publishedYes

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Messenger RNA
Proteins
Apoptosis
Experimental Melanomas
Caspase Inhibitors
Fibrosarcoma
Chemotactic Factors
Caspases
small inducible cytokine subfamily E, member 1
Hypoxia
Granulocytes
Confocal Microscopy
Monocytes
Neoplasms
Necrosis
Embryonic Structures
Tumor Necrosis Factor-alpha
Cytokines
In Vitro Techniques

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Matschurat, S., Knies, U. E., Person, V., Fink, L., Stoelcker, B., Ebenebe, C., ... Clauss, M. (2003). Regulation of EMAP II by hypoxia. American Journal of Pathology, 162(1), 93-103.

Regulation of EMAP II by hypoxia. / Matschurat, Susanne; Knies, Ulrike E.; Person, Veronika; Fink, Ludger; Stoelcker, Benjamin; Ebenebe, Chinedu; Behrensdorf, Heike A.; Schaper, Jutta; Clauss, Matthias.

In: American Journal of Pathology, Vol. 162, No. 1, 01.01.2003, p. 93-103.

Research output: Contribution to journalArticle

Matschurat, S, Knies, UE, Person, V, Fink, L, Stoelcker, B, Ebenebe, C, Behrensdorf, HA, Schaper, J & Clauss, M 2003, 'Regulation of EMAP II by hypoxia', American Journal of Pathology, vol. 162, no. 1, pp. 93-103.
Matschurat S, Knies UE, Person V, Fink L, Stoelcker B, Ebenebe C et al. Regulation of EMAP II by hypoxia. American Journal of Pathology. 2003 Jan 1;162(1):93-103.
Matschurat, Susanne ; Knies, Ulrike E. ; Person, Veronika ; Fink, Ludger ; Stoelcker, Benjamin ; Ebenebe, Chinedu ; Behrensdorf, Heike A. ; Schaper, Jutta ; Clauss, Matthias. / Regulation of EMAP II by hypoxia. In: American Journal of Pathology. 2003 ; Vol. 162, No. 1. pp. 93-103.
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