PAMAM Nanoparticles Promote Acute Lung Injury by Inducing Autophagic Cell Death through the Akt-TSC2-mTOR Signaling Pathway

被引：211

作者：

Li, Chenggang ^{[1
]}

Liu, Haolin ^{[1
]}

Sun, Yang ^{[1
]}

Wang, Hongliang ^{[1
]}

Guo, Feng ^{[1
]}

Rao, Shuan ^{[1
]}

Deng, Jiejie ^{[1
]}

Zhang, Yanli ^{[1
]}

Miao, Yufa ^{[2
]}

Guo, Chenying ^{[3
]}

Meng, Jie ^{[4
]}

Chen, Xiping ^{[5
]}

Li, Limin ^{[5
]}

Li, Dangsheng ^{[6
]}

Xu, Haiyan ^{[4
]}

Wang, Heng ^{[3
]}

Li, Bo ^{[2
]}

Jiang, Chengyu ^{[1
]}

机构：

[1] Chinese Acad Med Sci, State Key Lab Med Mol Biol, Dept Biochem & Mol Biol, Inst Basic Med Sci,Peking Union Med Coll, Beijing 100005, Peoples R China

[2] Natl Ctr Safety Evaluat Drugs, Natl Inst Control Pharmaceut & Biol Prod, Beijing Econ & Technol Dev Area, Beijing 100176, Peoples R China

[3] Chinese Acad Med Sci, Mol Parasitol Lab, Dept Etiol, Inst Basic Med Sci,Peking Union Med Coll, Beijing 100005, Peoples R China

[4] Chinese Acad Med Sci, Dept Biol Sci & Med Engn, Inst Basic Med Sci, Peking Union Med Coll, Beijing 100005, Peoples R China

[5] Chinese Acad Med Sci, Dept Pathol, Inst Basic Med Sci, Peking Union Med Coll, Beijing 100005, Peoples R China

[6] Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China

来源：

JOURNAL OF MOLECULAR CELL BIOLOGY | 2009年 / 1卷 / 01期

基金：

中国国家自然科学基金;

关键词：

PAMAM; nanoparticles; autophagy; acute lung injury; Akt; TSC2; mTOR;

D O I：

10.1093/jmcb/mjp002

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Nanotechnology is an important and emerging industry with a projected annual market of around one trillion US dollars by 2011-2015. Concerns about the toxicity of nanomaterials in humans, however, have recently been raised. Although studies of nanoparticle toxicity have focused on lung disease the molecular link between nanoparticle exposure and lung injury remained unclear. In this report, we show that cationic Starburst polyamidoamine dendrimer (PAMAM), a class of nanomaterials that are being widely developed for clinical applications can induce acute lung injury in vivo. PAMAM triggers autophagic cell death by deregulating the Akt-TSC2-mTOR signaling pathway. The autophagy inhibitor 3-methyladenine rescued PAMAM dendrimer-induced cell death and ameliorated acute lung injury caused by PAMAM in mice. Our data provide a molecular explanation for nanoparticle-induced lung injury, and suggest potential remedies to address the growing concerns of nanotechnology safety.

引用

页码：37 / 45

页数：9

共 35 条

[1] Apoptosis in murine lymphoid organs following intraperitoneal administration of dimethyl sulfoxide (DMSO) [J].