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Fibrinogen Interaction with Astrocyte ICAM-1 and PrPC Results in the Generation of ROS and Neuronal Death.
Sulimai, Nurul; Brown, Jason; Lominadze, David.
Afiliação
  • Sulimai N; Department of Surgery, University of South Florida Morsani College of Medicine, FL 33612 Tampa, USA.
  • Brown J; Department of Surgery, University of South Florida Morsani College of Medicine, FL 33612 Tampa, USA.
  • Lominadze D; Department of Surgery, University of South Florida Morsani College of Medicine, FL 33612 Tampa, USA.
Int J Mol Sci ; 22(5)2021 Feb 27.
Article em En | MEDLINE | ID: mdl-33673626
Many neuroinflammatory diseases, like traumatic brain injury (TBI), are associated with an elevated level of fibrinogen and short-term memory (STM) impairment. We found that during TBI, extravasated fibrinogen deposited in vasculo-astrocyte interfaces, which was associated with neurodegeneration and STM reduction. The mechanisms of this fibrinogen-astrocyte interaction and its functional role in neurodegeneration are still unclear. Cultured mouse brain astrocytes were treated with fibrinogen in the presence or absence of function-blocking antibody or peptide against its astrocyte receptors intercellular adhesion molecule-1 (ICAM-1) or cellular prion protein (PrPC), respectively. Fibrinogen interactions with astrocytic ICAM-1 and PrPC were characterized. The expression of pro-inflammatory markers, generations of reactive oxygen species (ROS) and nitric oxide (NO) in astrocytes, and neuronal death caused by astrocyte-conditioned medium were assessed. Data showed a strong association between fibrinogen and astrocytic ICAM-1 or PrPC, overexpression of pro-inflammatory cytokines and overproduction of ROS and NO, resulting in neuronal apoptosis and death. These effects were reduced by blocking the function of astrocytic ICAM-1 and PrPC, suggesting that fibrinogen association with its astrocytic receptors induce the release of pro-inflammatory cytokines, resulting in oxidative stress, and ultimately neuronal death. This can be a mechanism of neurodegeneration and the resultant STM reduction seen during TBI.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fibrinogênio / Astrócitos / Espécies Reativas de Oxigênio / Apoptose / Proteínas PrPC / Molécula 1 de Adesão Intercelular / Neurônios Limite: Animals Idioma: En Revista: Int J Mol Sci Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fibrinogênio / Astrócitos / Espécies Reativas de Oxigênio / Apoptose / Proteínas PrPC / Molécula 1 de Adesão Intercelular / Neurônios Limite: Animals Idioma: En Revista: Int J Mol Sci Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos