サトウ　アツシ   佐藤　淳    所属   応用生物学部 応用生物学科    職種   教授
言語種別	英語
発行・発表の年月	2024/01
形態種別	学術論文
査読	査読あり
標題	Intracellularly delivered human lactoferrin functions as an activator of Na+/H+ exchanger 7
執筆形態	共著
掲載誌名	Biochemical and Biophysical Research Communications
掲載区分	国外
出版社・発行元	Elsevier
巻・号・頁	695
担当区分	責任著者
著者・共著者	Daisuke Kurimoto , Truong Dinh Hue Anh , Ryoya Kasama , Atsushi Sato
概要	Here, we report that human lactoferrin (hLF), known for its anticancer properties, induced intracellular activation of the Na+/H+ exchanger (NHE) 7 in human lung cancer PC-9 cells. Compared to non-fused hLF, the fusion of human serum albumin (HSA) with hLF (hLF-HSA) facilitated its internalization into PC-9 cells in a caveolae-mediated manner, thereby exhibiting enhanced anti-proliferative effects. Although hLF alone did not exhibit any discernible effects, hLF-HSA resulted in organelle alkalization as detected using an acidotropic pH indicator. hLF-HSA-induced elevation of organelle pH and inhibition of cancer growth were abolished by NHE7 siRNA. hLF-HSA upregulated NHE7. Thus, upon cellular uptake, hLF-HSA triggers proton leakage through the upregulation of NHE7. This process led to organelle alkalization, probably in the trans-Golgi network (TGN) as suggested by the localization of NHE7 in PC-9 cells, thereby suppressing lung cancer cell growth. Forcing the cellular uptake of hLF alone using a caveolae-mediated endocytosis activator led to an increase in organelle pH. Furthermore, cell entry of hLF also activated proton-loading NHE7, leading to organelle acidification in the pancreatic cancer cell line MIA PaCa-2. Therefore, the intracellularly delivered hLF functions as an activator of NHE7.
外部リンクURL	https://www.sciencedirect.com/science/article/pii/S0006291X24000135