1,4-Naphthoquinone Induces FcRn Protein Expression and Albumin Recycling in Human THP-1 Cells

Abstract

The neonatal Fc receptor (FcRn) has been established as a major factor in regulating the metabolism of albumin and IgG in humans by protecting them from intracellular degradation after they are endocytosed into cells. We assume that increasing the levels of endogenous FcRn proteins in cells would be beneficial to enhance the recycling of these molecules. In this study, we identify the compound 1,4-naphthoquinone as an efficient stimulator of FcRn protein expression in human THP-1 monocytic cells with potency at the submicromolar range. Also, the compound increased the subcellular localization of FcRn to the endocytic recycling compartment and enhanced human serum albumin recycling in the PMA-induced THP-1 cells. These results suggest that 1,4-naphthoquinone stimulates FcRn expression and activity in human monocytic cells in vitro and it could open a new avenue for designing cotreatment agents to enhance the efficacy of biological treatments such as albumin-conjugated drugs in vivo .

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“…FcRn binding contributes greatly to the very long serum half-life of albumin. [29] As the binding of ABD-Tri to albumin showed little impact on its FcRn binding, ABD-Tri would also exhibit a long serum half-life once it formed a stable complex with albumin. To determine the pharmacokinetics of the complex of ABD-Tri and albumin, biotin-labeled ABD-Tri (Bio-ABD-Tri) mixed with MSA (Bio-ABD-Tri + MSA), biotin-labeled MSA (Bio-MSA) mixed with ABD-Tri (Bio-MSA + ABD-Tri), and biotin-labeled control peptide Z-Tri (Bio-Z-Tri) mixed with MSA (Bio-Z-Tri + MSA) were intravenously injected into mice, followed by dynamic measurement of the biotin-labeled proteins using ELISA.…”