Banca de DEFESA: CAROLINE MARTINS SANDANIELO MARQUES

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
DISCENTE : CAROLINE MARTINS SANDANIELO MARQUES
DATA : 22/09/2021
HORA: 13:30
LOCAL: Santo André - modo remoto
TÍTULO:

THE ACTION OF CELLULAR PRION PROTEIN IN THE INTERNALIZATION OF METALLIC IONS AND SOD1 UNDER OXIDATIVE STRESS AND NEURODEGENERATION

PÁGINAS: 116
GRANDE ÁREA: Ciências Exatas e da Terra
ÁREA: Química
SUBÁREA: Química Inorgânica
ESPECIALIDADE: Química Bio-Inorgânica
RESUMO:

Cellular prion protein (PrPC), in its native conformation, exerts numerous cellular and cognitive functions in brain tissue. However, with every search regarding its functions in recent years, doubts remain about its action and especially about how the molecular interaction of PrPC in neurodegenerative processes takes place. PrPC can also bind to divalent metals, especially copper. However, the functional meanings of this metal-protein interaction are still not completely clear. The objective of this work is to elucidate the participation of PrPC in the internalization of metals during episodes of oxidative stress and in cell neurodegeneration. For this, astrocytes from wild-type mice (WT) and knockout for PrPC (KO) were used, and the levels of intracellular metals are being evaluated, as well as verification of changes in the expression and localization of specific proteins such as SOD1, Tau and caspases under these conditions in order to establish relationships with PrPC. The results of this study indicate that the presence of PrPC indicates greater resistance in the cell viability of astrocytes when subjected to induction of oxidative stress with hydrogen peroxide (H2O2) and induction of neurodegeneration with the toxic oligomer of beta amyloid protein (AβO) according to the MTT and Trypan Blue assays. It was also possible to observe changes in basal levels of metals, and associate them with the condition of induced damage, indicating that PrPC is active in metal homeostasis, where the absence of PrPC leads to metallic unbalance, culminating in cellular vulnerability in oxidative and neurodegereactive processes. The results of the Western Blotting assay showed activation of specific proteins at different levels of each strain, such as caspase 3, Tau, phosphorylated Tau, p53 and Bcl2, being able to compare them and establish a relationship between PrPC and the induced damage condition, thus tracing evidence that the cellular prion protein acts with a neuroprotective role against oxidative stress and neurodegenerative process for astrocytes. By immunocytochemistry it was found that PrPC prevents the internalization of AβO and/or promotes its degradation under induction of neurodegeneration. It was also observed that the cellular prion protein is responsible for taking SOD1 to the nucleus under conditions of oxidative stress, probably acting in the control of DNA damage. The results obtained by the evaluation of protein aggregation confirmed that PrPC prevents protein aggregation under neurodegenerative conditions, showing once again its neuroprotective role in astrocyte cells.

MEMBROS DA BANCA:
Presidente - Interno ao Programa - 1544365 - GISELLE CERCHIARO
Membro Titular - Examinador(a) Externo ao Programa - 1640114 - MARCELA SORELLI CARNEIRO RAMOS
Membro Titular - Examinador(a) Externo ao Programa - 1696841 - LUCIANO PUZER
Membro Titular - Examinador(a) Externo ao Programa - 1672728 - ANA CAROLINA SANTOS DE SOUZA GALVAO
Membro Titular - Examinador(a) Externo à Instituição - MARILENE HOHMUT LOPES - USP
Membro Suplente - Examinador(a) Interno ao Programa - 1844792 - AMEDEA BAROZZI SEABRA
Membro Suplente - Examinador(a) Externo ao Programa - 1669152 - DANIEL CARNEIRO CARRETTIERO
Membro Suplente - Examinador(a) Externo à Instituição - BRENO PANNIA ESPÓSITO - USP