PAMAM nanoparticles promote acute lung injury by inducing autophagic cell death through the Akt-TSC2-mTOR signaling pathway.

Abstract	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.
Authors	Chenggang Li, Haolin Liu, Yang Sun, Hongliang Wang, Feng Guo, Shuan Rao, Jiejie Deng, Yanli Zhang, Yufa Miao, Chenying Guo, Jie Meng, Xiping Chen, Limin Li, Dangsheng Li, Haiyan Xu, Heng Wang, Bo Li, Chengyu Jiang
Journal	Journal of molecular cell biology (J Mol Cell Biol) Vol. 1 Issue 1 Pg. 37-45 (Oct 2009) ISSN: 1759-4685 [Electronic] United States
PMID	19516051 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Dendrimers Intracellular Signaling Peptides and Proteins PAMAM Starburst Polyamines TSC2 protein, human Tsc2 protein, mouse Tuberous Sclerosis Complex 2 Protein Tumor Suppressor Proteins MTOR protein, human mTOR protein, mouse Protein Serine-Threonine Kinases Proto-Oncogene Proteins c-akt TOR Serine-Threonine Kinases
Topics	Acute Lung Injury (chemically induced, enzymology, pathology) Animals Autophagy (drug effects) Cell Line, Tumor Dendrimers Humans Intracellular Signaling Peptides and Proteins (metabolism) Mice Nanoparticles (toxicity, ultrastructure) Polyamines (toxicity) Protein Serine-Threonine Kinases (metabolism) Proto-Oncogene Proteins c-akt (metabolism) Signal Transduction (drug effects) Survival Analysis TOR Serine-Threonine Kinases Tuberous Sclerosis Complex 2 Protein Tumor Suppressor Proteins (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!