RRC ID 62809
Author Endo M, Ohba K, Sato S, Yokota Y, Takahashi K.
Title Increased soluble (pro)renin receptor protein by autophagy inhibition in cultured cancer cells.
Journal Genes Cells
Abstract (Pro)renin receptor ((P)RR) regulates the renin-angiotensin system and functions as an essential accessory subunit of vacuolar H+ -ATPase. There is accumulating evidence that shows close relationship between (P)RR and autophagy. Soluble (P)RR consisting of the extracellular domain of (P)RR is generated from (P)RR by proteolytic enzymes. The aim of the present study was to clarify the influence of autophagy inhibition on soluble (P)RR expression in cancer cells. Autophagy was inhibited by treatment of bafilomycin A1 or chloroquine in MCF-7 and A549 cells for 72 hr. Western blot analysis showed that protein levels of soluble (P)RR were markedly elevated by autophagy inhibition, whereas no noticeable increases were observed in full-length (P)RR. Secretion of soluble (P)RR into the medium was increased dose-dependently by bafilomycin A1 or chloroquine. Autophagy inhibition was confirmed by enhanced accumulation of autophagy-related proteins, LC3, p62 and LAMP1 in intracellular vesicles. Increased amount of soluble (P)RR by autophagy inhibition was decreased by site-1 protease inhibitor, whereas no noticeable increase in site-1 protease immunoreactivity was observed in cells with autophagy inhibition by immunocytochemistry. These findings suggest that soluble (P)RR protein accumulates by autophagy inhibition, possibly because of the reduced degradation of soluble (P)RR in the intracellular vesicles during autophagy inhibition.
Volume 25(7)
Pages 483-497
Published 2020-7-1
DOI 10.1111/gtc.12776
PMID 32314441
MeSH Autophagy / drug effects* Autophagy / genetics Cell Line, Tumor Chloroquine / pharmacology Cytoplasmic Vesicles / metabolism Enzyme Inhibitors / pharmacology Furin / metabolism Humans Lysosome-Associated Membrane Glycoproteins / metabolism Macrolides / pharmacology Microtubule-Associated Proteins / metabolism Peptide Hydrolases / metabolism Protease Inhibitors / pharmacology RNA-Binding Proteins / metabolism Receptors, Cell Surface / genetics Receptors, Cell Surface / metabolism* Renin / metabolism* Vacuolar Proton-Translocating ATPases / genetics Vacuolar Proton-Translocating ATPases / metabolism*
IF 1.655
Human and Animal Cells MCF7(RCB1904) A549(RCB0098)