The biological functions of polyamine oxidation products by amine oxidases:Perspectives of clinical applications

摘要

The polyamines spermine,spermidine and putrescine are ubiquitous cell components.If they accumulate excessively within the cells,due either to very high extracellular concentrations or to deregulation of the systems which control polyamine homeostasis,they can induce toxic effects.These molecules are substrates of a class of enzymes that includes monoamine oxidases,diamine oxidases,polyamine oxidases and copper containing amine oxidases.Polyamine concentrations are high in growing tissues such as tumors.Amine oxidases are important because they contribute to regulate levels of mono- and polyamines.These enzymes catalyze the oxidative deamination of biogenic amines and polyamines to generate the reaction products H_2O_2 and aldehyde(s) that are able to induce cell death in several cultured human tumor cell lines.H_2O_2 generated by the oxidation reaction is able to cross the inner membrane of mitochondria and directly interact with endogenous molecules and structures,inducing an intense oxidative stress.Since amine oxidases are involved in many crucial physiopathological processes,investigations on their involvement in human diseases offer great opportunities to enter novel classes of therapeutic agents.