INVESTIGADORES
OGGERO EBERHARDT Marcos Rafael
artículos
Título:
Isolation and characterization of a subset of erythropoietin glycoforms with cytoprotective but minimal erythropoietic activity
Autor/es:
MÓNICA MATTIO; NATALIA CEAGLIO; MARCOS OGGERO; NORMA PEROTTI; IGNACIO AMADEO; GUSTAVO OROZCO; GUILLERMINA FORNO; RICARDO KRATJE; MARINA ETCHEVERRIGARAY
Revista:
Biotechnology Progress
Editorial:
Wiley Blackwell
Referencias:
Año: 2011 vol. 27 p. 1018 - 1028
ISSN:
1520-6033
Resumen:
Although historically used for the treatment of anemia, erythropoietin (EPO) has emerged as a neurotrophic and neuroprotective agent in different conditions of neuronal damage (traumatic brain injury, ischemia, spinal cord compression, peripheral neuropathy, retinal damage, epilepsy, Parkinson?s Disease, among others. Nonetheless, EPO?s therapeutic application is limited due to its hematological side-effects. With the aim of obtaining EPO derivatives resembling the hormone isolated from cells and tissues of neural origin, a novel combination of less acidic EPO glycoforms -designated as neuroepoetin (rhNEPO)- was purified to homogeneity from the supernatant of a CHO-producing cell line by a four-step chromatographic procedure. This simple and single process allowed us to prepare two EPO derivatives with distinct therapeutic expectations: the hematopoietic version and a minimally hematopoietic, but mainly in vitro cytoprotective, alternative. Further biological characterization showed that the in vivo erythropoietic activity of rhNEPO was 25-times lower than that of rhEPO. Interestingly, using different in vitro cytoprotective assays we found that this molecule exerts cytoprotection equivalent to, or better than, that of rhEPO in cells of neural phenotype. Furthermore, despite its shorter plasma half-life, rhNEPO was rapidly absorbed and promptly detected in the cerebrospinal fluid after intravenous administration in rats (5 min post-injection, in comparison with 30 min for rhEPO). Therefore, our results support the study of neuroepoetin as a potential drug for the treatment of neurological diseases, combining high cytoprotective activity with reduced hematological side-effects.
