Increased soluble (pro)renin receptor protein by autophagy inhibition in cultured cancer cells.,Genes to Cells

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Increased soluble (pro)renin receptor protein by autophagy inhibition in cultured cancer cells.
Genes to Cells ( IF 1.3 ) Pub Date : 2020-04-20 , DOI: 10.1111/gtc.12776
Moe Endo ₁ , Koji Ohba ₁ , Shigemitsu Sato ₁ , Yurina Yokota ₁ , Kazuhiro Takahashi ₁

Affiliation

(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.

中文翻译：

通过在培养的癌细胞中抑制自噬来增加可溶性肾素（原）受体蛋白。

(Pro)肾素受体 ((P)RR) 调节肾素-血管紧张素系统，并作为液泡 H ⁺ ATP 酶的重要辅助亚基发挥作用。越来越多的证据表明(P)RR与自噬之间存在密切关系。由 (P)RR 胞外结构域组成的可溶性 (P)RR 由 (P)RR 通过蛋白水解酶产生。本研究的目的是阐明自噬抑制对癌细胞中可溶性 (P)RR 表达的影响。用巴弗洛霉素 A1 或氯喹处理 MCF-7 和 A549 细胞 72 小时，可抑制自噬。蛋白质印迹分析表明，自噬抑制可显着提高可溶性 (P)RR 的蛋白水平，而全长 (P)RR 则没有观察到明显的增加。巴弗洛霉素 A1 或氯喹可剂量依赖性地增加可溶性 (P)RR 向培养基中的分泌。自噬相关蛋白、LC3、p62 和 LAMP1 在细胞内囊泡中积累的增加证实了自噬抑制。位点 1 蛋白酶抑制剂可减少自噬抑制导致的可溶性 (P)RR 量的增加，而通过免疫细胞化学检测，在自噬抑制的细胞中未观察到位点 1 蛋白酶免疫反应性明显增加。这些发现表明，可溶性 (P)RR 蛋白通过自噬抑制而积累，可能是因为自噬抑制期间细胞内囊泡中可溶性 (P)RR 的降解减少。

更新日期：2020-04-20

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