The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Protection against ischemic brain injury by protein therapeutics
Open accessAbstract
Preventing massive cell death is an important therapeutic strategy for various injuries and disorders. Protein therapeutics have the advantage of delivering proteins in a short period. We have engineered the antiapoptotic bcl-x gene to generate the super antiapoptotic factor, FNK, with a more powerful cytoprotective activity. In this study, we fused the protein transduction domain (PTD) of the HIV/Tat protein to FNK and used the construct in an animal model of ischemic brain injury. When added into culture media of human neuroblastoma cells and rat neocortical neurons, PTD-FNK rapidly transduced into cells and localized to mitochondria within 1 h. It protected the neuroblastomas and neurons against staurosporine-induced apoptosis and glutamate-induced excitotoxicity, respectively. The cytoprotective activity of PTD-FNK was found at concentrations as low as 0.3 pM. Additionally, PTD-FNK affected the cytosolic movement of calcium ions, which may relate to its neuroprotective action. Immunohistochemical analysis revealed that myc-tagged PTD-FNK (PTD-myc-FNK) injected i.p. into mice can have access into brain neurons. When injected i.p. into gerbils, PTD-FNK prevented delayed neuronal death in the hippocampus caused by transient global ischemia. These results suggest that PTD-FNK has a potential for clinical utility as a protein therapeutic strategy to prevent cell death in the brain.
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Cites
Translocation of SAPK/JNK to Mitochondria and Interaction with Bcl-xL in Response to DNA Damage
Kharbanda, S., Saxena, S., Yoshida, K., Pandey, P., Kaneki, M., Wang, Q., Cheng, K., Chen, Y.-N., Campbell, A., Sudha, T., et al. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.1.322 · Cited by 429
Cited by
Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals
Ohsawa, I., Ishikawa, M., Takahashi, K., Watanabe, M., Nishimaki, K., Yamagata, K., Katsura, K.-I., Katayama, Y., Asoh, S., & Ohta, S. (2007) · Nature Medicine · doi:10.1038/nm1577 · Cited by 2,560
Self-citationGUPTA, B., LEVCHENKO, T., & TORCHILIN, V (2005) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2004.10.007 · Cited by 632
RECENT APPROACHES TO INTRACELLULAR DELIVERY OF DRUGS AND DNA AND ORGANELLE TARGETING
Torchilin, V. P. (2006) · Annual Review of Biomedical Engineering · doi:10.1146/annurev.bioeng.8.061505.095735 · Cited by 543
Delivery of bioactive molecules into the cell: the Trojan horse approach
Dietz, G. P. H., & Bähr, M. (2004) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2004.03.005 · Cited by 469
Cell-penetrating peptides as delivery vehicles for biology and medicine
Stewart, K. M., Horton, K. L., & Kelley, S. O. (2008) · Organic & Biomolecular Chemistry · doi:10.1039/b719950c · Cited by 381
Metadata
- Authors
- Asoh, S., Ohsawa, I., Mori, T., Katsura, K.-I., Hiraide, T., Katayama, Y., Kimura, M., Ozaki, D., Yamagata, K., & Ohta, S.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2002-12-10
- Volume
- 99
- Issue
- 26
- Pages
- 17107-17112
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1968479682
- Cited by
- 198
- References
- 1
- FWCI
- 7.34
- Type
- journal article
- Language
- en
- Open access
- green
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- Asoh, S., Ohsawa, I., Mori, T., Katsura, K.-I., Hiraide, T., Katayama, Y., Kimura, M., Ozaki, D., Yamagata, K., & Ohta, S. (2002). Protection against ischemic brain injury by protein therapeutics. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.262460299
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