CYTOTOXICITY ARISING FROM IRON ACCUMULATION AND BETA AMYLOID PEPTIDE: EXPLORING POTENTIAL NEUROPROTECTIVE ROLES OF ERYTHROPOIETIN AND ITS CARBAMYLATED DERIVATIVE

MACIEL PACCINI, JUAN IGNACIO; MALTANERI, ROMINA EUGENIA; WETZER DIANA; NESSE ALCIRA; CHAMORRO, MARÍA EUGENIA; VITTORI, DANIELA

Congreso; LXVIII Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica; 2023

SAIC-SAI-FAIC-SAFIS

Evidence suggests the accumulation of iron (Fe) in connection with senescence and neurodegenerative diseases, alongside the aggregation of the β-amyloid (βA) peptide. Numerous aspects of Alzheimer's disease (AD) pathogenesis align with ferroptosis indicators, such as the generation of oxidative stress due to Fe overload. The potential neuroprotective impact of erythropoietin (Epo) against these detriments prompts inquiries regarding its role within the Central Nervous System (CNS). Our goal was to probe into whether the cytoprotective effects of Epo and its non-erythropoietic carbamylated derivative, cEpo, could counter these AD signs.Evaluation of Epo's structural alteration revealed that cEpo exhibited altered mobility due to the inhibition of positive charges (SDS-PAGE and Zone Capillary Electrophoresis), yet its secondary structure remained unaffected (Circular Dichroism). In Epo-dependent UT-7 cell line cultures (MTT assay), cEpo displayed no erythropoietic potential; however, it retained its protective influence against staurosporine-triggered apoptosis in the SH-SY5Y neuroblastoma cell line (Flow Cytometry: increase in annexin-positive cells).The addition of βA aggregates (preincubated at 37°C, 1 µM) to SH-SY5Y cell cultures induced apoptosis. Both Epo and cEpo (50 U/mL) prevented this outcome (Annexin C 1.00; **βA 2.9±0.80, Epo-βA 1.8±0.32, cEpo-βA 1.0±0.21 a.u. Mean±SEM (n=4), **significant differences vs. C, P