Autophagy is a new protective mechanism against the cytotoxicity of platinum nanoparticles in human trophoblasts

被引:29
|
作者
Nakashima, Akitoshi [1 ]
Higashisakaz, Kazuma [1 ,3 ]
Kusabiraki, Tae [1 ]
Aoki, Aiko [1 ]
Ushijima, Akemi [1 ]
Ono, Yosuke [1 ]
Tsuda, Sayaka [1 ]
Shima, Tomoko [1 ]
Yoshino, Osamu [1 ,7 ]
Nagano, Kazuya [2 ]
Yoshioka, Yasuo [2 ,4 ,5 ]
Tsutsumi, Yasuo [2 ,6 ]
Saito, Shigeru [1 ]
机构
[1] Univ Toyama, Dept Obstet & Gynecol, 2630 Sugitani, Toyama 9300194, Japan
[2] Osaka Univ, Grad Sch Pharmaceut Sci, Lab Toxicol & Safety Sci, 1-6 Yamadaoka, Suita, Osaka 5650871, Japan
[3] Osaka Univ, Grad Sch Med, Dept Legal Med, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan
[4] Osaka Univ, Res Inst Microbial Dis, BIKEN Innovat Vaccine Res Alliance Labs, Vaccine Creat Project, 3-1 Yamadaoka, Suita, Osaka 5650871, Japan
[5] Osaka Univ, Res Fdn Microbial Dis, BIKEN Ctr Innovat Vaccine Res & Dev, 3-1 Yamadaoka, Suita, Osaka 5650871, Japan
[6] Osaka Univ, Ctr Adv Med Engn & Informat, 1-6 Yamadaoka, Suita, Osaka 5650871, Japan
[7] Kitasato Univ, Sch Med, Dept Obstet & Gynecol, Minami Ku, 1-15-1 Kitazato, Sagamihara, Kanagawa 2520374, Japan
关键词
NANOSTRUCTURED MATERIALS; PREGNANCY COMPLICATIONS; SILVER NANOPARTICLES; GOLD NANOPARTICLES; POOR PLACENTATION; AIR-POLLUTION; CELL-DEATH; PREECLAMPSIA; TOXICITY; SIZE;
D O I
10.1038/s41598-019-41927-2
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Nanoparticles are widely used in commodities, and pregnant women are inevitably exposed to these particles. The placenta protects the growing fetus from foreign or toxic materials, and provides energy and oxygen. Here we report that autophagy, a cellular mechanism to maintain homeostasis, engulfs platinum nanoparticles (nPt) to reduce their cytotoxicity in trophoblasts. Autophagy was activated by nPt in extravillous trophoblast (EVT) cell lines, and EVT functions, such as invasion and vascular remodeling, and proliferation were inhibited by nPt. These inhibitory effects by nPt were augmented in autophagy-deficient cells. Regarding the dynamic state of nPt, analysis using ICP-MS demonstrated a higher accumulation of nPt in the autophagosome-rich than the cytoplasmic fraction in autophagy-normal cells. Meanwhile, there were more nPt in the nuclei of autophagy-deficient cells, resulting in greater DNA damage at a lower concentration of nPt. Thus, we found a new protective mechanism against the cytotoxicity of nPt in human trophoblasts.
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页数:13
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