Fibrinogen Interaction with Astrocyte ICAM-1 and PrP<sup>C</sup> Results in the Generation of ROS and Neuronal Death
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/5/2391 |
| _version_ | 1797417310962581504 |
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| author | Nurul Sulimai Jason Brown David Lominadze |
| author_facet | Nurul Sulimai Jason Brown David Lominadze |
| author_sort | Nurul Sulimai |
| collection | DOAJ |
| description | 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 (PrP<sup>C</sup>), respectively. Fibrinogen interactions with astrocytic ICAM-1 and PrP<sup>C</sup> 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 PrP<sup>C</sup>, 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 PrP<sup>C</sup>, 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. |
| first_indexed | 2024-03-09T06:16:55Z |
| format | Article |
| id | doaj.art-9d15d71d583648c49e5293c04e3f9efe |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T06:16:55Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9d15d71d583648c49e5293c04e3f9efe2023-12-03T11:52:31ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01225239110.3390/ijms22052391Fibrinogen Interaction with Astrocyte ICAM-1 and PrP<sup>C</sup> Results in the Generation of ROS and Neuronal DeathNurul Sulimai0Jason Brown1David Lominadze2Department of Surgery, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USADepartment of Surgery, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USADepartment of Surgery, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USAMany 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 (PrP<sup>C</sup>), respectively. Fibrinogen interactions with astrocytic ICAM-1 and PrP<sup>C</sup> 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 PrP<sup>C</sup>, 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 PrP<sup>C</sup>, 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.https://www.mdpi.com/1422-0067/22/5/2391apoptosispro-inflammatory markersneuronNOproximity ligationROS |
| spellingShingle | Nurul Sulimai Jason Brown David Lominadze Fibrinogen Interaction with Astrocyte ICAM-1 and PrP<sup>C</sup> Results in the Generation of ROS and Neuronal Death International Journal of Molecular Sciences apoptosis pro-inflammatory markers neuron NO proximity ligation ROS |
| title | Fibrinogen Interaction with Astrocyte ICAM-1 and PrP<sup>C</sup> Results in the Generation of ROS and Neuronal Death |
| title_full | Fibrinogen Interaction with Astrocyte ICAM-1 and PrP<sup>C</sup> Results in the Generation of ROS and Neuronal Death |
| title_fullStr | Fibrinogen Interaction with Astrocyte ICAM-1 and PrP<sup>C</sup> Results in the Generation of ROS and Neuronal Death |
| title_full_unstemmed | Fibrinogen Interaction with Astrocyte ICAM-1 and PrP<sup>C</sup> Results in the Generation of ROS and Neuronal Death |
| title_short | Fibrinogen Interaction with Astrocyte ICAM-1 and PrP<sup>C</sup> Results in the Generation of ROS and Neuronal Death |
| title_sort | fibrinogen interaction with astrocyte icam 1 and prp sup c sup results in the generation of ros and neuronal death |
| topic | apoptosis pro-inflammatory markers neuron NO proximity ligation ROS |
| url | https://www.mdpi.com/1422-0067/22/5/2391 |
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