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.
Recent evidence implicates endogenous opioid systems in basic processes which underlie morphogenesis. The present report describes a population of cells within the germinal zone of the neonatal rat forebrain which are immunoreactive for the opioid peptide beta-endorphin and other peptides derived from the proopiomelanocortin precursor. These cells are present at the time of birth, but are no longer detectable by the sixth postnatal day. They have medially and laterally directed processes which extend to the ventricular wall and across the caudate putamen to its lateral border. Cells of similar morphology and distribution which are immunoreactive for two other proopiomelanocortin peptides, alpha-melanocyte stimulating hormone and adrenocorticotrophic hormone, were also observed in similar distributions during the same developmental period. These data are consistent with the hypothesis that cells within the germinal zone transiently synthesize proopiomelanocortin, which is further processed to yield these three peptide products. This finding may be important in understanding the role of proopiomelanocortin-derived peptides in neural development.
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