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Title
Japanese:Calciprotein particle-induced cytotoxicity via lysosomal dysfunction and altered cholesterol distribution in renal epithelial HK-2 cells 
English:Calciprotein particle-induced cytotoxicity via lysosomal dysfunction and altered cholesterol distribution in renal epithelial HK-2 cells 
Author
Japanese: 國重莉奈, Mai Mizoguchi, Asako Tsubouchi, Kenjiro Hanaoka, Yutaka Miura, Hiroshi Kurosu, 浦野 泰照, Makoto Kuro-o, 村田 昌之.  
English: Rina Kunishige, Mai Mizoguchi, Asako Tsubouchi, Kenjiro Hanaoka, Yutaka Miura, Hiroshi Kurosu, Yasuteru Urano, Makoto Kuro-o, Masayuki Murata.  
Language English 
Journal/Book name
Japanese:Scientific Reports 
English:Scientific Reports 
Volume, Number, Page Vol. 10    No. 1   
Published date Dec. 2020 
Publisher
Japanese: 
English: 
Conference name
Japanese: 
English: 
Conference site
Japanese: 
English: 
Official URL http://dx.doi.org/10.1038/s41598-020-77308-3
 
DOI https://doi.org/10.1038/s41598-020-77308-3
Abstract <jats:title>Abstract</jats:title><jats:p>Dietary phosphate overload induces chronic kidney disease (CKD), and calciprotein particles (CPPs), a form of nanoparticle comprising calcium phosphate and serum proteins, has been proposed to cause renal toxicity. However, the mechanism of CPP cytotoxicity in renal tubular cells is unknown. Here we show that in renal proximal tubular epithelial HK-2 cells, endocytosed CPPs accumulate in late endosomes/lysosomes (LELs) and increase their luminal pH by ~ 1.0 unit. This results in a decrease in lysosomal hydrolase activity and autophagic flux blockage without lysosomal rupture and reactive oxygen species generation. CPP treatment led to vulnerability to H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub>-induced oxidative stress and plasma membrane injury, probably because of autophagic flux blockage and decreased plasma membrane cholesterol, respectively. CPP-induced disruption of lysosomal homeostasis, autophagy flux and plasma membrane integrity might trigger a vicious cycle, leading to progressive nephron loss.</jats:p>

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