Phosphothioated oligodeoxynucleotides induce nonspecific effects on neuronal cell adhesion in a growth substrate-dependent manner
✍ Scribed by Eitan Okun; Mark P. Mattson
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 295 KB
- Volume
- 87
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Abstract
Synthetic phosphothioated (PTO) oligodeoxynucleotide (ODN) sequences are commonly used for a variety of applications that benefit from nuclease protection. The PTO modification is implemented mainly in antisense ODN, but also in ODN that were shown to activate members of the toll‐like receptor (TLR) family such as TLR3 (poly‐I:C), TLR8 (ssRNA), and TLR9 (CpG). Neurons are routinely plated on surfaces coated with either cationic substances such as poly‐L‐ornithine (PLO), polyethylenimine (PEI), poly‐L‐lysine or ECM components such as laminin, collagen, or fibronectin. We found that PTO‐ODN aimed at activating TLR9 induces a non‐TLR9‐specific detachment phenotype in cortical neurons plated on either laminin or PEI, but not on PLO. This phenotype was correlated with decreased viability and was partially inhibited when caspase‐3 was inhibited with Ac‐DEVD‐CMK. This finding suggests that the use of PTO‐ODN can cause nonspecific effects on cell adhesion that could compromise interpretation of data from experiments using PTO‐ODN. © 2009 Wiley‐Liss, Inc.