Compositions for detecting cell death and methods of use thereof

摘要

The invention provides compounds and methods of their use in the detection of apoptosis and necrosis both in vitro and in vivo. Also provided are compounds and methods of their use in selective delivery of agents to cells undergoing apoptosis or necrosis. The compounds and methods are based on conjugates formed with a dehydrogenase such as lactate dehydrogenase, alcohol dehydrogenase, aldehyde dehydrogenase, and malate dehydrogenase. The compounds and methods are useful in the diagnosis and treatment of conditions characterized by apoptosis, including cancer, cardiac disease, neurologic disease including stroke, and autoimmunity. The compounds and methods offer distinct advantages over corresponding compounds and methods based on Annexin V. Also provided are methods for screening for compounds that modulate, i.e., inhibit or promote, apoptosis.

主权项

1. A method for detecting cells undergoing early apoptosis cell death, the method comprising:
contacting a test population of cells with a conjugate of a dehydrogenase linked to a detectable label, under conditions suitable for uptake of the conjugate by the test population of cells, wherein the dehydrogenase is a lactate dehydrogenase (LDH), alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH) or malate dehydrogenase (MDH); and detecting the label in the test population of cells, wherein presence of the label in the test population of cells indicates cells undergoing early apoptosis.