Dr Fernando Torres Andón, PhD University of Santiago de Compostela AECC Researcher in Nanomedicine for Cancer Immunotherapy Nanomedicine - Cancer Immunotherapy - Nanotoxicology - Cell Death Santiago de Compostela, A Coruña | Spain
Acc Chem Res 2013 Mar 21;46(3):733-42. Epub 2012 Jun 21.
Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Engineered nanomaterials offer numerous and tantalizing opportunities in many sectors of society, including medicine. Needless to say, attention should also be paid to the potential for unexpected hazardous effects of these novel materials. To date, much of the nanotoxicology literature has focused on the assessment of cell viability or cell death using primitive assays for the detection of plasma membrane integrity or mitochondrial function or assessment of cellular morphology. However, when assessing the cytotoxic effects of engineered nanomaterials, researchers need not only to consider whether cells are dead or alive but also to assess which of the numerous, highly specific pathways of cell death might be involved. Moreover, it is important to diagnose cell death based not only on morphological markers but on the assessment and quantification of biochemical alterations specific to each form of cell death. In this Account, we provide a description of the three major forms of programmed cell death in mammalian cells: apoptosis, autophagic cell death, and regulated necrosis, sometimes referred to as necroptosis. Apoptosis can be activated via the extrinsic (death receptor-dependent) or via the intrinsic (mitochondria-dependent) route. Apoptotic cell death may or may not require the activation of cytosolic proteases known as caspases. Autophagy (self-eating) has an important homeostatic role in the cell, mediating the removal of dysfunctional or damaged organelles thereby allowing the recycling of cellular building blocks. However, unrestrained autophagy can kill cells. Studies in recent years have revealed that necrosis that depends on activation of the kinases RIP1 and RIP3 is a major form of programmed cell death with roles in development and immunity. We also discuss recent examples of the impact of engineered nanoparticles on the three different pathways of programmed cell death. For example, acute exposure of cells to carbon nanotubes (CNTs) can induce apoptosis whereas chronic exposure to CNTs may yield an apoptosis-resistant and tumorigenic phenotype in lung epithelial cells. Several reports show that nanoparticles, including polystyrene particles, are routed to the lysosomal compartment and trigger cell death through the destabilization of lysosomal membranes with engagement of the intrinsic apoptosis pathway. In addition, a number of studies have demonstrated that nanomaterials such as CNTs, quantum dots, and gold nanoparticles can affect cellular autophagy. An improved understanding of the complexities of the nanomaterial-induced perturbation of different cell death pathways may allow for a better prediction of the consequences of human exposure.
We have submitted your request - we will update you on status within the next 24 hours.
Sign up for further access to Scientific Publications and Authors!
What are PubFacts Points?
PubFacts points are rewards to PubFacts members, which allow you to better promote your profile and articles throughout PubFacts.com
How do I earn PubFacts Points?
Each member is given 50 PubFacts points upon signing up. You can earn additional points by completing 100% of your profile, creating and participating in discussions, and sharing other members research.
What can I do with PubFacts Points?
Currently, you can use PubFacts Points to promote and increase readership of your articles.