J Cell Biochem. 2012 Jun;113(6):1955-65. doi: 10.1002/jcb.24064.

Pro-apoptotic gene knockdown mediated by nanocomplexed siRNA reduces radiation damage in primary salivary gland cultures.

Arany S, Xu Q, Hernady E, Benoit DS, Dewhurst S, Ovitt CE.

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Center for Oral Biology, Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA. szilvia_arany@urmc.rochester.edu

Abstract

A critical issue in the management of head and neck tumors is radioprotection of the salivary glands. We have investigated whether siRNA-mediated gene knock down of pro-apoptotic mediators can reduce radiation-induced cellular apoptosis in salivary gland cells in vitro. We used novel, pH-responsive nanoparticles to deliver functionally active siRNAs into cultures of salivary gland cells. The nanoparticle molecules are comprised of cationic micelles that electrostatically interact with the siRNA, protecting it from nuclease attack, and also include pH-responsive endosomolytic constituents that promote release of the siRNA into the target cell cytoplasm. Transfection controls with Cy3-tagged siRNA/nanoparticle complexes showed efficiently internalized siRNAs in more than 70% of the submandibular gland cells. We found that introduction of siRNAs specifically targeting the Pkcδ or Bax genes significantly blocked the induction of these pro-apoptotic proteins that normally occurs after radiation in cultured salivary gland cells. Furthermore, the level of cell death from subsequent radiation, as measured by caspase-3, TUNEL, and mitochondrial disruption assays, was significantly decreased. Thus, we have successfully demonstrated that the siRNA/nanoparticle-mediated knock down of pro-apoptotic genes can prevent radiation-induced damage in submandibular gland primary cell cultures.

PMID:: 22253051; [PubMed - indexed for MEDLINE]
PMCID:: PMC3360791; [Available on 2013/6/1]

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(Arany S[Author] AND (Q, Xu[Full Author Name] OR (Q, Xu[Full Author Name] OR Xu Q[Author] OR Xu Q[Investigator]) OR Xu Q[Investigator]) AND Hernady E[Author] AND Benoit DS[Author] AND (Dewhurst S[Author] OR Dewhurst S[Investigator]) AND Ovitt CE[Author]) AND 2012[All Fields] AND (Pro-apoptotic[All Fields] AND ("gene knockdown techniques"[MeSH Terms] OR ("gene"[All Fields] AND "knockdown"[All Fields] AND "techniques"[All Fields]) OR "gene knockdown techniques"[All Fields] OR ("gene"[All Fields] AND "knockdown"[All Fields]) OR "gene knockdown"[All Fields]) AND mediated[All Fields] AND nanocomplexed[All Fields] AND ("rna, small interfering"[MeSH Terms] OR ("rna"[All Fields] AND "small"[All Fields] AND "interfering"[All Fields]) OR "small interfering rna"[All Fields] OR "sirna"[All Fields]) AND reduces[All Fields] AND ("radiation"[MeSH Terms] OR "radiation"[All Fields] OR "electromagnetic radiation"[MeSH Terms] OR ("electromagnetic"[All Fields] AND "radiation"[All Fields]) OR "electromagnetic radiation"[All Fields]) AND damage[All Fields] AND primary[All Fields] AND ("salivary glands"[MeSH Terms] OR ("salivary"[All Fields] AND "glands"[All Fields]) OR "salivary glands"[All Fields] OR ("salivary"[All Fields] AND "gland"[All Fields]) OR "salivary gland"[All Fields]) AND ("culture"[MeSH Terms] OR "culture"[All Fields] OR "cultures"[All Fields]) AND "J Cell Biochem"[Journal] AND 113[All Fields]) AND 6[All Fields] AND 1955-1965[All Fields]

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Pro-apoptotic gene knockdown mediated by nanocomplexed siRNA reduces radiation d...
Pro-apoptotic gene knockdown mediated by nanocomplexed siRNA reduces radiation damage in primary salivary gland cultures.
J Cell Biochem. 2012 Jun ;113(6):1955-65. doi: 10.1002/jcb.24064.

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(Arany S[Author] AND (Q, Xu[Full Author Name] OR Xu Q[Author] OR ... (1)
(Arany S[Author] AND (Q, Xu[Full Author Name] OR Xu Q[Author] OR Xu Q[Investigator]) AND Hernady E[Author] AND Benoit DS[Author] AND (Dewhurst S[Author] OR Dewhurst S[Investigator]) AND Ovitt CE[Author]) AND 2012[All Fields] AND (Pro-apoptotic[All Fields] AND ("gene knockdown techniques"[MeSH Terms] OR ("gene"[All Fields] AND "knockdown"[All Fields] AND "techniques"[All Fields]) OR "gene knockdown techniques"[All Fields] OR ("gene"[All Fields] AND "knockdown"[All Fields]) OR "gene knockdown"[All Fields]) AND mediated[All Fields] AND nanocomplexed[All Fields] AND ("rna, small interfering"[MeSH Terms] OR ("rna"[All Fields] AND "small"[All Fields] AND "interfering"[All Fields]) OR "small interfering rna"[All Fields] OR "sirna"[All Fields]) AND reduces[All Fields] AND ("radiation"[MeSH Terms] OR "radiation"[All Fields] OR "electromagnetic radiation"[MeSH Terms] OR ("electromagnetic"[All Fields] AND "radiation"[All Fields]) OR "electromagnetic radiation"[All Fields]) AND damage[All Fields] AND primary[All Fields] AND ("salivary glands"[MeSH Terms] OR ("salivary"[All Fields] AND "glands"[All Fields]) OR "salivary glands"[All Fields] OR ("salivary"[All Fields] AND "gland"[All Fields]) OR "salivary gland"[All Fields]) AND ("culture"[MeSH Terms] OR "culture"[All Fields] OR "cultures"[All Fields]) AND "J Cell Biochem"[Journal] AND 113[All Fields]) AND 6[All Fields] AND 1955-1965[All Fields]
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