Vitamin D-Binding Protein Acts in the Actin Scavenge System and Can Have Increased Expression During Aspirin Therapy

Abstract

While the clinical efficacy of aspirin in cerebral thrombosis prevention has been well established, its mechanism of action is still controversial. In an effort to better understand these mechanisms and to identify potential biomarkers, comparative proteomic analysis between 18 patients both pre-aspirin treatment at the time of cerebral thrombotic onset (control group) and post-aspirin treatment (experiment group) was carried out using two-dimensional gel electrophoresis (2-DE) in combination with matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDITOF/ MS). Of the 228 2-DE identified differentially expressed protein spots, 11 proteins showed more than a 1.5-fold difference. Of these, vitamin D-binding protein (DBP) and actin were further examined via Western blot and showed consistent results, with DBP levels significantly increased post-aspirin treatment (114.04 ± 16.69) relative to pre-treatment (66.33 ± 5.61) while actin showed the opposite trend (p < 0.01 for both comparisons). Next, co-immunoprecipitation analysis of DBP and actin showed direct binding. Furthermore, a protein-protein interaction network of DBP and the other differentially expressed proteins was constructed using Ingenuity Pathway Analysis software. These results suggest that DBP acts in the actin scavenge system and consequently the increase in DBP levels correlated with aspirin therapy in cerebral thrombotic patients. These findings also suggest that aspirin may prevent platelet aggregation and thrombosis through the actions of DBP and other DBP related proteins.

Proteomics Approach for the Discovery of Rheumatoid Arthritis Biomarkers Using Mass Spectrometry

“…VDBP is known as an actin-scavenging protein. When tissues are damaged in RA, cells with increased permeability secrete F-actin, which corresponds to polymerized actin [21,22,23]. As a result, blood vessels are blocked, leading to pathological conditions such as microthrombosis.…”

Identification of serum proteins in dogs naturally infected with Anaplasma phagocytophilum and Borrelia burgdorferi: a pilot study

“…Decreased VDBP content in dogs with VBDs may be related to decreased synthesis with/or excessive use of proteins in the liver that can have an impact on circulating vitamin D levels, leading to negative effects on the immune response of the host against infections, such as VBDs (Uysal et al, 2015). Possible tissue and/or organ injury as well as coagulation activation during both infections in dogs can cause alterations in serum VDBP levels (Bottari et al, 2016;Li et al, 2016). The overuse of vitamin D to neutralize the overproduction of ferritin and transferrin in response to VBDs may also be the reason for the decrease in VDBP in this study (Escribano et al, 2017, Kules et al, 2014Kuleś et al, 2016).…”

Commentary: Serum Vitamin D Levels Are Associated With Increased COVID-19 Severity and Mortality Independent of Whole-Body and Visceral Adiposity

“…Furthermore, aspirin treatment resulted in considerably greater DBP concentrations post-aspirin treatment compared to pre-treatment in cerebral thrombotic patients, but the reverse event was observed for actin. Aspirin, through the activities of DBP and other DBP-related proteins, may inhibit platelet aggregation and thrombosis ( 11 ).…”