Abstract
The pathological role of vitamin K2 in Alzheimer’s disease (AD) involves a definite link between impaired cognitive functions and decreased serum vitamin K levels. Vitamin K2 supplementation may have a protective effect on AD. However, the mechanism underlying vitamin K2 protection has not been elucidated. With the amyloid-β (Aβ) cascade hypothesis, we constructed a clone containing the C-terminal fragment of amyloid precursor protein (β-CTF/APP), transfected in astroglioma C6 cells and used this cell model (β-CTF/C6) to study the protective effect of vitamin K2 against Aβ cytotoxicity. Both cellular and biochemical assays, including cell viability and reactive oxygen species (ROS), assays assay, and Western blot and caspase activity analyses, were used to characterize and unveil the protective role and mechanism of vitamin K2 protecting against Aβ-induced cytotoxicity. Vitamin K2 treatment dose-dependently decreased the death of neural cells. The protective effect of vitamin K2 could be abolished by adding warfarin, a vitamin K2 antagonist. The addition of vitamin K2 reduced the ROS formation and inhibited the caspase-3 mediated apoptosis induced by Aβ peptides, indicating that the mechanism underlying the vitamin K2 protection is likely against Aβ-mediated apoptosis. Inhibitor assay and Western blot analyses revealed that the possible mechanism of vitamin K2 protection against Aβ-mediated apoptosis might be via regulating phosphatidylinositol 3-kinase (PI3K) associated-signaling pathway and inhibiting caspase-3-mediated apoptosis. Our study demonstrates that vitamin K2 can protect neural cells against Aβ toxicity.
Highlights
Accepted: 11 March 2021Alzheimer’s disease (AD) is the most common form of neurodegenerative disease [1,2].AD patients usually experience a progressive loss of cognitive function, memory, and intellectual activity [2,3]
We constructed a β-CTF/C6 cell line and applied this system to study the effect of vitamin K2 on AD
Results suggest that vitamin K2 could significantly inhibit the caspase-mediated apoptosis induced by Aβ toxicity
Summary
Alzheimer’s disease (AD) is the most common form of neurodegenerative disease [1,2]. AD patients usually experience a progressive loss of cognitive function, memory, and intellectual activity [2,3]. Amyloid-β (Aβ) peptide plays an important role in AD pathogenesis and is the main component of senile plaques [2,4,5]. Aβ accumulation is a determining factor in AD [4,6,7,8,9]. The accumulation of Aβ involves a structural change from an α-helix to a β-strand and deposition into toxic aggregated species, such as oligomers or fibrils. Toxic Aβ aggregates have been shown to cause neural cell death by apoptosis or necrosis [7,10]
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