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Molecular interaction of fibrinogen with zeolite nanoparticles.

ABSTRACT: Fibrinogen is one of the key proteins that participate in the protein corona composition of many types of nanoparticles (NPs), and its conformational changes are crucial for activation of immune systems. Recently, we demonstrated that the fibrinogen highly contributed in the protein corona composition at the surface of zeolite nanoparticles. Therefore, understanding the interaction of fibrinogen with zeolite nanoparticles in more details could shed light of their safe applications in medicine. Thus, we probed the molecular interactions between fibrinogen and zeolite nanoparticles using both experimental and simulation approaches. The results indicated that fibrinogen has a strong and thermodynamically favorable interaction with zeolite nanoparticles in a non-cooperative manner. Additionally, fibrinogen experienced a substantial conformational change in the presence of zeolite nanoparticles through a concentration-dependent manner. Simulation results showed that both E- and D-domain of fibrinogen are bound to the EMT zeolite NPs via strong electrostatic interactions, and undergo structural changes leading to exposing normally buried sequences. D-domain has more contribution in this interaction and the C-terminus of ? chain (?377-394), located in D-domain, showed the highest level of exposure compared to other sequences/residues.

SUBMITTER: Derakhshankhah H

PROVIDER: S-EPMC6367512 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Molecular interaction of fibrinogen with zeolite nanoparticles.

Derakhshankhah Hossein H Hosseini Atiyeh A Taghavi Fereshteh F Jafari Samira S Lotfabadi Alireza A Ejtehadi Mohammad Reza MR Shahbazi Sahba S Fattahi Ali A Ghasemi Atiyeh A Barzegari Ebrahim E Evini Mina M Saboury Ali Akbar AA Shahri Seyed Mehdi Kamali SMK Ghaemi Behnaz B Ng Eng-Poh EP Awala Hussein H Omrani Fatemeh F Nabipour Iraj I Raoufi Mohammad M Dinarvand Rassoul R Shahpasand Koorosh K Mintova Svetlana S Hajipour Mohammad Javad MJ Mahmoudi Morteza M

Scientific reports 20190207 1

Fibrinogen is one of the key proteins that participate in the protein corona composition of many types of nanoparticles (NPs), and its conformational changes are crucial for activation of immune systems. Recently, we demonstrated that the fibrinogen highly contributed in the protein corona composition at the surface of zeolite nanoparticles. Therefore, understanding the interaction of fibrinogen with zeolite nanoparticles in more details could shed light of their safe applications in medicine. T ...[more]

PMID: 30733474

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Project description:Essentials Evidence suggests a comorbidity between hyperhomocysteinemia (HHC) and Alzheimer's disease (AD). Homocysteine (HC) could affect the ?-amyloid (A?)-fibrinogen interaction in AD pathology. AD patients with concomitant HHC have increased fibrin and A? deposits in their brains. HC contributes to AD pathology via the A?-fibrinogen interaction.Background Accumulating clinical evidence suggests that hyperhomocysteinemia (HHC) is correlated with Alzheimer's disease (AD) and vascular dementia. Objective This study was carried out to elucidate the specific role of elevated homocysteine (HC) levels in AD pathophysiology. Methods Immunohistochemistry was used to examine ?-amyloid (A?) deposition along blood vessels, also known as cerebral amyloid angiopathy (CAA), fibrin(ogen) deposition, and their correlation to each other in the brains of AD patients with and without HHC. To study AD-HHC co-morbidity in detail, an AD mouse model was administered a high methionine diet for several months. Parenchymal A? plaques, CAA-positive vessels and fibrin deposits were then assessed by immunohistochemistry at different stages of AD progression. Memory deficits were evaluated with contextual fear conditioning and the Barnes maze. Additionally, the effect of HC and its metabolite, homocysteine thiolactone (HCTL), on the A?-fibrinogen interaction was analyzed by pull-down, ELISA and fibrin clot formation and fibrinolysis assays in vitro. Results We found increased fibrin(ogen) levels and A? deposits in the blood vessels and brain parenchyma of AD patients with HHC. We demonstrate that HC and HCTL enhance the interaction between fibrinogen and A?, promote the formation of tighter fibrin clots and delay clot fibrinolysis. Additionally, we show that diet-induced HHC in an AD mouse model leads to severe CAA and parenchymal A? deposition, as well as significant impairments in learning and memory. Conclusions These findings suggest that elevated levels of plasma HC/HCTL contribute to AD pathology via the A?-fibrin(ogen) interaction.

Dataset Information

Molecular interaction of fibrinogen with zeolite nanoparticles.

Publications

Molecular interaction of fibrinogen with zeolite nanoparticles.

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