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Noninvasive Imaging of Cell Death Using an Hsp90 Ligand
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2011-03-09 , DOI: 10.1021/ja110226y
Danielle Park 1 , Anthony S Don , Tania Massamiri , Amol Karwa , Beth Warner , Jan MacDonald , Christine Hemenway , Arati Naik , Kah-Tiong Kuan , Pierre J Dilda , Jason W H Wong , Kevin Camphausen , Lori Chinen , Mary Dyszlewski , Philip J Hogg
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2011-03-09 , DOI: 10.1021/ja110226y
Danielle Park 1 , Anthony S Don , Tania Massamiri , Amol Karwa , Beth Warner , Jan MacDonald , Christine Hemenway , Arati Naik , Kah-Tiong Kuan , Pierre J Dilda , Jason W H Wong , Kevin Camphausen , Lori Chinen , Mary Dyszlewski , Philip J Hogg
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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 (111)In-tagged compound. This versatile compound should enable the imaging of cell death in most experimental settings.
中文翻译：
使用 Hsp90 配体对细胞死亡进行无创成像
细胞死亡在正常生理和疾病中起着核心作用。凋亡和坏死细胞死亡的共同点是质膜完整性的最终丧失。我们生产了一种小的有机砷化合物 4-(N-(S-glutathionylacetyl)amino) phenylarsonous 酸，它在死亡细胞的细胞质中迅速积累，同时失去质膜完整性。该化合物主要通过与 90 kDa 热休克蛋白 (Hsp90)（真核细胞质中最丰富的分子伴侣）的共价反应保留在细胞质中。有机砷被标记为光学或放射性同位素报告组，以在体外和原位对培养细胞和鼠肿瘤中的细胞死亡进行成像。使用 (111) In 标记化合物通过 SPECT/CT 对小鼠的肿瘤细胞死亡进行非侵入性成像。
更新日期：2011-03-09
中文翻译：
使用 Hsp90 配体对细胞死亡进行无创成像
细胞死亡在正常生理和疾病中起着核心作用。凋亡和坏死细胞死亡的共同点是质膜完整性的最终丧失。我们生产了一种小的有机砷化合物 4-(N-(S-glutathionylacetyl)amino) phenylarsonous 酸，它在死亡细胞的细胞质中迅速积累，同时失去质膜完整性。该化合物主要通过与 90 kDa 热休克蛋白 (Hsp90)（真核细胞质中最丰富的分子伴侣）的共价反应保留在细胞质中。有机砷被标记为光学或放射性同位素报告组，以在体外和原位对培养细胞和鼠肿瘤中的细胞死亡进行成像。使用 (111) In 标记化合物通过 SPECT/CT 对小鼠的肿瘤细胞死亡进行非侵入性成像。
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