Effects of fetuin-A-containing calciprotein particles on posttranslational modifications of fetuin-A in HepG2 cells

Abstract Fetuin-A is an inhibitor of ectopic calcification that is expressed mainly in hepatocytes and is secreted into the circulation after posttranslational processing, including glycosylation and phosphorylation. The molecular weight (MW) of fully modified fetuin-A (FM-fetuin-A) is approximately...

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Autores principales:	Hideki Uedono, Katsuhito Mori, Akinobu Ochi, Shinya Nakatani, Yuya Miki, Akihiro Tsuda, Tomoaki Morioka, Yuki Nagata, Yasuo Imanishi, Tetsuo Shoji, Masaaki Inaba, Masanori Emoto
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/03689133350140b5824577f32340636f
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spelling	oai:doaj.org-article:03689133350140b5824577f32340636f2021-12-02T14:17:19ZEffects of fetuin-A-containing calciprotein particles on posttranslational modifications of fetuin-A in HepG2 cells10.1038/s41598-021-86881-02045-2322https://doaj.org/article/03689133350140b5824577f32340636f2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86881-0https://doaj.org/toc/2045-2322Abstract Fetuin-A is an inhibitor of ectopic calcification that is expressed mainly in hepatocytes and is secreted into the circulation after posttranslational processing, including glycosylation and phosphorylation. The molecular weight (MW) of fully modified fetuin-A (FM-fetuin-A) is approximately 60 kDa in an immunoblot, which is much higher than the estimated MW by amino acid sequence. Under conditions of calcification stress such as advanced stage chronic kidney disease, fetuin-A prevents calcification by forming colloidal complexes, which are referred to as calciprotein particles (CPP). Since the significance of CPP in this process is unclear, we investigated the effect of synthetic secondary CPP on the level of FM-fetuin-A in HepG2 cells. Secondary CPP increased the level of FM-fetuin-A in dose- and time-dependent manners, but did not affect expression of mRNA for fetuin-A. Treatment with O- and/or N-glycosidase caused a shift of the 60 kDa band of FM-fetuin-A to a lower MW. Preincubation with brefeldin A, an inhibitor of transport of newly synthesized proteins from the endoplasmic reticulum to the Golgi apparatus, completely blocked the secondary CPP-induced increase in FM-fetuin-A. Treatment with BAPTA-AM, an intracellular calcium chelating agent, also inhibited the CPP-induced increase in the FM-fetuin-A level. Secondary CPP accelerate posttranslational processing of fetuin-A in HepG2 cells.Hideki UedonoKatsuhito MoriAkinobu OchiShinya NakataniYuya MikiAkihiro TsudaTomoaki MoriokaYuki NagataYasuo ImanishiTetsuo ShojiMasaaki InabaMasanori EmotoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hideki Uedono Katsuhito Mori Akinobu Ochi Shinya Nakatani Yuya Miki Akihiro Tsuda Tomoaki Morioka Yuki Nagata Yasuo Imanishi Tetsuo Shoji Masaaki Inaba Masanori Emoto Effects of fetuin-A-containing calciprotein particles on posttranslational modifications of fetuin-A in HepG2 cells
description	Abstract Fetuin-A is an inhibitor of ectopic calcification that is expressed mainly in hepatocytes and is secreted into the circulation after posttranslational processing, including glycosylation and phosphorylation. The molecular weight (MW) of fully modified fetuin-A (FM-fetuin-A) is approximately 60 kDa in an immunoblot, which is much higher than the estimated MW by amino acid sequence. Under conditions of calcification stress such as advanced stage chronic kidney disease, fetuin-A prevents calcification by forming colloidal complexes, which are referred to as calciprotein particles (CPP). Since the significance of CPP in this process is unclear, we investigated the effect of synthetic secondary CPP on the level of FM-fetuin-A in HepG2 cells. Secondary CPP increased the level of FM-fetuin-A in dose- and time-dependent manners, but did not affect expression of mRNA for fetuin-A. Treatment with O- and/or N-glycosidase caused a shift of the 60 kDa band of FM-fetuin-A to a lower MW. Preincubation with brefeldin A, an inhibitor of transport of newly synthesized proteins from the endoplasmic reticulum to the Golgi apparatus, completely blocked the secondary CPP-induced increase in FM-fetuin-A. Treatment with BAPTA-AM, an intracellular calcium chelating agent, also inhibited the CPP-induced increase in the FM-fetuin-A level. Secondary CPP accelerate posttranslational processing of fetuin-A in HepG2 cells.
format	article
author	Hideki Uedono Katsuhito Mori Akinobu Ochi Shinya Nakatani Yuya Miki Akihiro Tsuda Tomoaki Morioka Yuki Nagata Yasuo Imanishi Tetsuo Shoji Masaaki Inaba Masanori Emoto
author_facet	Hideki Uedono Katsuhito Mori Akinobu Ochi Shinya Nakatani Yuya Miki Akihiro Tsuda Tomoaki Morioka Yuki Nagata Yasuo Imanishi Tetsuo Shoji Masaaki Inaba Masanori Emoto
author_sort	Hideki Uedono
title	Effects of fetuin-A-containing calciprotein particles on posttranslational modifications of fetuin-A in HepG2 cells
title_short	Effects of fetuin-A-containing calciprotein particles on posttranslational modifications of fetuin-A in HepG2 cells
title_full	Effects of fetuin-A-containing calciprotein particles on posttranslational modifications of fetuin-A in HepG2 cells
title_fullStr	Effects of fetuin-A-containing calciprotein particles on posttranslational modifications of fetuin-A in HepG2 cells
title_full_unstemmed	Effects of fetuin-A-containing calciprotein particles on posttranslational modifications of fetuin-A in HepG2 cells
title_sort	effects of fetuin-a-containing calciprotein particles on posttranslational modifications of fetuin-a in hepg2 cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/03689133350140b5824577f32340636f
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Effects of fetuin-A-containing calciprotein particles on posttranslational modifications of fetuin-A in HepG2 cells

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