Nanosized polyamidoamine (PAMAM) dendrimer-induced apoptosis mediated by mitochondrial dysfunction.
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.
Lee
Jong-Ho
JH
Department of Bioscience and Biotechnology, Hankuk University of Foreign Studies, Yong-In, Gyung-Gi Do 449-791, Republic of Korea.
Cha
Kyung Eun
KE
Kim
Min Soo
MS
Hong
Hye Won
HW
Chung
Dong June
DJ
Ryu
Gyuha
G
Myung
Heejoon
H
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
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