Noninvasive imaging of cell death using an Hsp90 ligand
| Autor: | Danielle Park, Christine L. Hemenway, Amol Karwa, Beth Warner, Tania Massamiri, Lori K. Chinen, Arati D. Naik, Jan MacDonald, Pierre J. Dilda, Philip J. Hogg, Kah Tiong Kuan, Kevin Camphausen, Jason W. H. Wong, Anthony S. Don, Mary Dyszlewski |
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| Rok vydání: | 2011 |
| Předmět: |
Programmed cell death
Biochemistry Catalysis Arsenicals Article Carcinoma Lewis Lung Jurkat Cells Mice Colloid and Surface Chemistry Heat shock protein Neoplasms Animals Humans HSP90 Heat-Shock Proteins Radioisotopes Mice Inbred BALB C biology Cell Death Chemistry General Chemistry Carbocyanines Pentetic Acid Ligand (biochemistry) Hsp90 Molecular biology Mice Inbred C57BL Cytosol Cytoplasm Apoptosis biology.protein Colorectal Neoplasms Peptides Ex vivo Protein Binding |
| Zdroj: | J Am Chem Soc |
| ISSN: | 1520-5126 |
| Popis: | Cell death plays a central role in normal physiology and in disease. Common to apoptotic and necrotic cell death is the eventual loss of plasma membrane integrity. We have produced a small organoarsenical compound, 4-(N-(S-glutathionylacetyl)amino)phenylarsonous acid, that rapidly accumulates in the cytosol of dying cells coincident with loss of plasma membrane integrity. The compound is retained in the cytosol predominantly by covalent reaction with the 90 kDa heat shock protein (Hsp90), the most abundant molecular chaperone of the eukaryotic cytoplasm. The organoarsenical was tagged with either optical or radioisotope reporting groups to image cell death in cultured cells and in murine tumors ex vivo and in situ. Tumor cell death in mice was noninvasively imaged by SPECT/CT using an (11)1In-tagged compound. This versatile compound should enable the imaging of cell death in most experimental settings. |
| Databáze: | OpenAIRE |
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