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Asialoerythropoietin is a nonerythropoietic cytokine with broad neuroprotective activity in vivo.

ABSTRACT: Erythropoietin (EPO) is a tissue-protective cytokine preventing vascular spasm, apoptosis, and inflammatory responses. Although best known for its role in hematopoietic lineages, EPO also affects other tissues, including those of the nervous system. Enthusiasm for recombinant human erythropoietin (rhEPO) as a potential neuroprotective therapeutic must be tempered, however, by the knowledge it also enlarges circulating red cell mass and increases platelet aggregability. Here we examined whether erythropoietic and tissue-protective activities of rhEPO might be dissociated by a variation of the molecule. We demonstrate that asialoerythropoietin (asialoEPO), generated by total enzymatic desialylation of rhEPO, possesses a very short plasma half-life and is fully neuroprotective. In marked contrast with rhEPO, this molecule at doses and frequencies at which rhEPO exhibited erythropoiesis, did not increase the hematocrit of mice or rats. AsialoEPO appeared promptly within the cerebrospinal fluid after i.v. administration; intravenously administered radioiodine-labeled asialoEPO bound to neurons within the hippocampus and cortex in a pattern corresponding to the distribution of the EPO receptor. Most importantly, asialoEPO exhibits a broad spectrum of neuroprotective activities, as demonstrated in models of cerebral ischemia, spinal cord compression, and sciatic nerve crush. These data suggest that nonerythropoietic variants of rhEPO can cross the blood-brain barrier and provide neuroprotection.

SUBMITTER: Erbayraktar S

PROVIDER: S-EPMC164517 | biostudies-literature | 2003 May

REPOSITORIES: biostudies-literature

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Asialoerythropoietin is a nonerythropoietic cytokine with broad neuroprotective activity in vivo.

Erbayraktar Serhat S Grasso Giovanni G Sfacteria Alessandra A Xie Qiao-wen QW Coleman Thomas T Kreilgaard Mads M Torup Lars L Sager Thomas T Erbayraktar Zubeyde Z Gokmen Necati N Yilmaz Osman O Ghezzi Pietro P Villa Pia P Fratelli Maddalena M Casagrande Simona S Leist Marcel M Helboe Lone L Gerwein Jens J Christensen Søren S Geist Marie Aavang MA Pedersen Lars Østergaard LØ Cerami-Hand Carla C Wuerth Jean-Paul JP Cerami Anthony A Brines Michael M

Proceedings of the National Academy of Sciences of the United States of America 20030513 11

Erythropoietin (EPO) is a tissue-protective cytokine preventing vascular spasm, apoptosis, and inflammatory responses. Although best known for its role in hematopoietic lineages, EPO also affects other tissues, including those of the nervous system. Enthusiasm for recombinant human erythropoietin (rhEPO) as a potential neuroprotective therapeutic must be tempered, however, by the knowledge it also enlarges circulating red cell mass and increases platelet aggregability. Here we examined whether e ...[more]

PMID: 12746497

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Dataset Information

Asialoerythropoietin is a nonerythropoietic cytokine with broad neuroprotective activity in vivo.

Publications

Asialoerythropoietin is a nonerythropoietic cytokine with broad neuroprotective activity in vivo.

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