TY - JOUR
T1 - Autophagy is a new protective mechanism against the cytotoxicity of platinum nanoparticles in human trophoblasts
AU - Nakashima, Akitoshi
AU - Higashisaka, Kazuma
AU - Kusabiraki, Tae
AU - Aoki, Aiko
AU - Ushijima, Akemi
AU - Ono, Yosuke
AU - Tsuda, Sayaka
AU - Shima, Tomoko
AU - Yoshino, Osamu
AU - Nagano, Kazuya
AU - Yoshioka, Yasuo
AU - Tsutsumi, Yasuo
AU - Saito, Shigeru
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85063905702&partnerID=8YFLogxK
U2 - 10.1038/s41598-019-41927-2
DO - 10.1038/s41598-019-41927-2
M3 - 学術論文
C2 - 30940860
AN - SCOPUS:85063905702
SN - 2045-2322
VL - 9
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 5478
ER -