title: Nanosized polyamidoamine (PAMAM) dendrimer-induced apoptosis mediated by mitochondrial dysfunction.
abstract: Nano-materials are currently being used in a variety of fields. One of the concerns associated with their use is their potential to harm human health. In an attempt to identify genes expressed differently in human lung cells (WI-26 VA4) exposed to nanosized (45 nm in diameter) PAMAM (polyamidoamine) dendrimers, we observed down-regulation of mitochondrial DNA-encoded genes involved in the maintenance of mitochondrial membrane potential. Down-regulation of gene expression was confirmed by semi-quantitative RT-PCR. Dendrimers were shown to colocalize with mitochondria and cause the release of cytochrome C. Mitochondrial membrane potential was disrupted and the viability of cells was decreased in the presence of dendrimers. Activation of caspases 3 and 9 was increased. Apoptosis was observed by annexin V/propidium iodide staining and DNA fragmentation. In summary, nanosized dendrimers damaged mitochondria resulting in apoptosis.
authors: Department of Bioscience and Biotechnology, Hankuk University of Foreign Studies, Yong-In, Gyung-Gi Do 449-791, Republic of Korea.
authors: Jong-Ho
authors: JH
authors: Lee
authors: Kyung Eun
authors: KE
authors: Cha
authors: Min Soo
authors: MS
authors: Kim
authors: Hye Won
authors: HW
authors: Hong
authors: Dong June
authors: DJ
authors: Chung
authors: Gyuha
authors: G
authors: Ryu
authors: Heejoon
authors: H
authors: Myung
mesh_terms: D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D004396:Coloring Agents; D045304:Cytochromes c / Q000378:metabolism; D050091:Dendrimers / Q000633:toxicity*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D020287:In Situ Nick-End Labeling; D008564:Membrane Potentials / Q000187:drug effects; D028361:Mitochondrial Diseases / Q000139:chemically induced* / Q000473:pathology*; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism; D053758:Nanoparticles; D011419:Propidium; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D017304:Annexin A5; D004396:Coloring Agents; D050091:Dendrimers; C522260:PAMAM G3.5 dendrimer; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D011419:Propidium; D045304:Cytochromes c; D053148:Caspase 3; D053453:Caspase 9