Esawi Ezaldeen Ismael, Mahmoud Ismail Sami, Abdullah Mohammad Salah, Abuarqoub Duaa Azmi, Ahram Mamoun Ahmad, Alshaer Walhan Mohammad
Department of Pathology and Laboratory Medicine, King Hussein Cancer Centre, Amman 11941, Jordan.
Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, The Hashemite University, Zarqa 13133, Jordan.
ACS Omega. 2023 Apr 25;8(18):16491-16499. doi: 10.1021/acsomega.3c01678. eCollection 2023 May 9.
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 and it could open a new avenue for designing cotreatment agents to enhance the efficacy of biological treatments such as albumin-conjugated drugs .
新生儿Fc受体(FcRn)已被确认为调节人体白蛋白和IgG代谢的主要因素,它通过保护白蛋白和IgG在被细胞内吞后免受细胞内降解来发挥作用。我们推测,提高细胞内源性FcRn蛋白水平将有助于增强这些分子的再循环。在本研究中,我们确定化合物1,4-萘醌是人类THP-1单核细胞中FcRn蛋白表达的有效刺激剂,其效力在亚微摩尔范围内。此外,该化合物增加了FcRn在内吞再循环区室的亚细胞定位,并增强了PMA诱导的THP-1细胞中人类血清白蛋白的再循环。这些结果表明,1,4-萘醌可刺激人类单核细胞中FcRn的表达和活性,这可能为设计联合治疗药物开辟一条新途径,以提高白蛋白偶联药物等生物治疗的疗效。