Nanomaterial induced apoptosis (WP2507)

Homo sapiens

Apotosis caused by nanomaterials, such as single-walled carbon nanohorns, titanium oxide, and polystyrene nanoparticles, may be induced through lysosomal impairment. For example, PAMAMs have been found to cause mitochondrial membrane destabilization, and silver and gold nanoparticles are reported to induce ER stress, which may lead to cytochrome c release from mitochondria. Proteins on this pathway have targeted assays available via the [ CPTAC Assay Portal]


Egon Willighagen , Anwesha Bohler , Bart Smeets , Friederike Ehrhart , Martina Summer-Kutmon , Fernando Torres Andón , Denise Slenter , Kristina Hanspers , Marvin Martens , and Finterly Hu


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Homo sapiens


Adverse Outcome Pathways Nanomaterials Pathways


Pathway Ontology

apoptotic cell death pathway nanomaterial response pathway


Label Type Compact URI Comment
TiO2 NP Metabolite None
Au NP Metabolite None
Polystyrene NP Metabolite chebi:134403
Nanohorn Metabolite None
DNA Metabolite chebi:16991
Ca2+ Metabolite pubchem.compound:271
PAMAM Metabolite None
Ag NP Metabolite None
BCL2 GeneProduct ensembl:ENSG00000171791
FADD GeneProduct ensembl:ENSG00000168040
CASP8 GeneProduct ensembl:ENSG00000064012
AIF GeneProduct ensembl:ENSG00000156709
SMAC/DIABLO GeneProduct ensembl:ENSG00000184047
CASP7 GeneProduct ensembl:ENSG00000165806
BAK GeneProduct ensembl:ENSG00000030110
FASLG GeneProduct ensembl:ENSG00000117560
CASP9 GeneProduct ensembl:ENSG00000132906
FLIP GeneProduct ensembl:ENSG00000003402
FAS GeneProduct ensembl:ENSG00000026103
tBID GeneProduct ensembl:ENSG00000015475
Cyt C GeneProduct ensembl:ENSG00000172115
APAF-1 GeneProduct ensembl:ENSG00000120868
CASP6 GeneProduct ensembl:ENSG00000138794
CASP3 GeneProduct ensembl:ENSG00000164305
BAX GeneProduct ensembl:ENSG00000087088
Perforin GeneProduct ensembl:ENSG00000180644
EndoG GeneProduct ensembl:ENSG00000167136
HTRA2/OMI GeneProduct ensembl:ENSG00000115317


  1. Cationic polystyrene nanosphere toxicity depends on cell-specific endocytic and mitochondrial injury pathways. Xia T, Kovochich M, Liong M, Zink JI, Nel AE. ACS Nano. 2008 Jan;2(1):85–96. PubMed Europe PMC Scholia
  2. Nanosized polyamidoamine (PAMAM) dendrimer-induced apoptosis mediated by mitochondrial dysfunction. Lee JH, Cha KE, Kim MS, Hong HW, Chung DJ, Ryu G, et al. Toxicol Lett. 2009 Oct 28;190(2):202–7. PubMed Europe PMC Scholia
  3. Carbon black and titanium dioxide nanoparticles elicit distinct apoptotic pathways in bronchial epithelial cells. Hussain S, Thomassen LCJ, Ferecatu I, Borot MC, Andreau K, Martens JA, et al. Part Fibre Toxicol. 2010 Apr 16;7:10. PubMed Europe PMC Scholia
  4. Endoplasmic reticulum stress signaling is involved in silver nanoparticles-induced apoptosis. Zhang R, Piao MJ, Kim KC, Kim AD, Choi JY, Choi J, et al. Int J Biochem Cell Biol. 2012 Jan;44(1):224–32. PubMed Europe PMC Scholia
  5. Identification of the nanogold particle-induced endoplasmic reticulum stress by omic techniques and systems biology analysis. Tsai YY, Huang YH, Chao YL, Hu KY, Chin LT, Chou SH, et al. ACS Nano. 2011 Dec 27;5(12):9354–69. PubMed Europe PMC Scholia
  6. Lysosomal membrane destabilization induced by high accumulation of single-walled carbon nanohorns in murine macrophage RAW 264.7. Tahara Y, Nakamura M, Yang M, Zhang M, Iijima S, Yudasaka M. Biomaterials. 2012 Mar;33(9):2762–9. PubMed Europe PMC Scholia
  7. Programmed cell death: molecular mechanisms and implications for safety assessment of nanomaterials. Andón FT, Fadeel B. Acc Chem Res. 2013 Mar 19;46(3):733–42. PubMed Europe PMC Scholia