Isatin, an endogenous nonpeptide biofactor: A review of its molecular targets, mechanisms of actions, and their biomedical implications.

Isatin (indole-2,3-dione) is an oxidized indole. It is widely distributed in mammalian tissues and body fluids, where isatin concentrations vary significantly from <0.1 to > 10 µM. Isatin output is increased under conditions of stress. Exogenously administered isatin is characterized by low toxicity, mutagenicity, and genotoxicity in vivo. Cytotoxic effects of isatin on various cell cultures are usually observed at concentrations exceeding 100 µM. Binding of [3 H]isatin to rat brain sections is consistent with its physiological concentrations. Proteomic analysis of mouse and rat brain isatin-binding proteins revealed about 90 individual proteins, which demonstrated significant interspecies differences (rat versus mouse). Certain evidence exist that redox state(s) and possibly other types of posttranslational modifications regulate affinity of target proteins to isatin. Recent data suggest that interacting with numerous intracellular isatin binding proteins, isatin can act as a regulator of complex protein networks in norm and pathology. Physiological concentrations of isatin in vitro inhibit monoamine oxidase B and natriuretic peptide receptor guanylate cyclase, higher (neuroprotective) concentrations (50-400 μM) cause apoptosis of various (including malignant tumor) cell lines and influence expression of certain apoptosis-related genes. Being administered in vivo, isatin exhibits various behavioral effects; it attenuates manifestations of MPTP-induced parkinsonism and tumor growth in experimental animal models.