Increased soluble (pro)renin receptor protein by autophagy inhibition in cultured cancer cells
Increased soluble (pro)renin receptor protein by autophagy inhibition in cultured cancer cells
复制标题
在培养的癌细胞中通过自噬抑制增加可溶性肾素（原）受体蛋白
DOI：
10.1111/gtc.12776
复制
发表时间：
2020
期刊：
影响因子：
2.1
通讯作者：
Takahashi Kazuhiro
中科院分区：
文献类型：
--
作者：
Endo Moe;Ohba Koji;Sato Shigemitsu;Yokota Yurina;Takahashi Kazuhiro
（Pro）renin receptor（（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与自噬有着密切的关系。由（P）RR的胞外结构域组成的可溶性（P）RR通过蛋白水解酶从（P）RR产生。本研究的目的是阐明自噬抑制对癌细胞可溶性（P）RR表达的影响。在MCF-7和A549细胞中，巴弗洛霉素A1或氯喹处理72小时可抑制自噬。蛋白质印迹分析表明，可溶性（P）RR的蛋白质水平通过自噬抑制显著升高，而全长（P）RR没有观察到明显的增加。巴弗洛霉素A1或氯喹剂量依赖性地增加了可溶性（P）RR向培养基中的分泌。细胞内囊泡中自噬相关蛋白LC 3、p62和LAMP 1的积累增强证实了自噬抑制作用。位点1蛋白酶抑制剂降低了自噬抑制引起的可溶性（P）RR增加量，而免疫细胞化学法在自噬抑制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，这可能是因为在自噬抑制期间细胞内囊泡中可溶性（P）RR的降解减少。
(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.
登录
查看更多内容
影响因子：
3
作者：
Hirose, Takuo;Mori, Nobuyoshi;Imai, Yutaka
通讯作者：
Imai, Yutaka
阻塞性睡眠呼吸暂停综合征患者血浆可溶性肾素（原）受体水平升高：与多导睡眠图参数的关联
影响因子：
3
作者：
Tsuguo Nishijima;Kazuki Tajima;Kazuhiro Takahashi;S. Sakurai
通讯作者：
S. Sakurai
影响因子：
5.5
作者：
Fang, Hui;Xu, Chuanming;Yang, Tianxin
通讯作者：
Yang, Tianxin
影响因子：
20.1
作者：
Kinouchi, Kenichiro;Ichihara, Atsuhiro;Itoh, Hiroshi
通讯作者：
Itoh, Hiroshi
影响因子：
3.5
作者：
Ramser, J;Abidi, FE;Nguyen, G
通讯作者：
Nguyen, G