Polyamine catabolism: target for antiproliferative therapies in animals and stress tolerance strategies in plants

Abstract

Metabolism of polyamines spermidine and spermine, and their diamine precursor, putrescine, has been a target for antineoplastic therapy since these naturally occurring alkyl amines were found essential for normal mammalian cell growth. Intracellular polyamine concentrations are maintained at a cell type-specific set point through the coordinated and highly regulated interplay between biosynthesis, transport, and catabolism. A correlation between regulation of cell proliferation and polyamine metabolism is described. In particular, polyamine catabolism involves copper-containing amine oxidases and FAD-dependent polyamine oxidases. Several studies showed an important role of these enzymes in several developmental and disease-related processes in both animals and plants through a control on polyamine homeostasis in response to normal cellular signals, drug treatment, environmental and/or cellular stressors. The production of toxic aldehydes and reactive oxygen species, H(2)O(2) in particular, by these oxidases using extracellular and intracellular polyamines as substrates, suggests a mechanism by which the oxidases can be exploited as antineoplastic drug targets. This minireview summarizes recent advances on the physiological roles of polyamine catabolism in animals and plants in an attempt to highlight differences and similarities that may contribute to determine in detail the underlined mechanisms involved. This information could be useful in evaluating the possibility of this metabolic pathway as a target for new antiproliferative therapies in animals and stress tolerance strategies in plants.

The Apoplastic Copper AMINE OXIDASE1 Mediates Jasmonic Acid-Induced Protoxylem Differentiation in Arabidopsis Roots

“…The polyamines (PAs) putrescine (Put), spermidine (Spd), and spermine (Spm) are small aliphatic polycations ubiquitous in living organisms and essential for cell growth, proliferation, and differentiation (Tavladoraki et al, 2012). In plants, PAs have been involved in a multiplicity of developmental processes as well as stress responses and tolerance strategies, their intracellular and extracellular levels varying in response to different physiological and pathological conditions (Mattoo et al, 2010).…”

“…In plants, PAs have been involved in a multiplicity of developmental processes as well as stress responses and tolerance strategies, their intracellular and extracellular levels varying in response to different physiological and pathological conditions (Mattoo et al, 2010). A fine regulation of their metabolism and/or transport ensures the occurrence of the appropriate PA levels depending on the specific cell needs (Tavladoraki et al, 2012). Oxidative deamination of PAs is catalyzed by amine oxidases (AOs) in a multistep mechanism, with the release of the removed amine moiety and amino aldehydes in the oxidative phase and the production of H 2 O 2 in the reoxidation step of the reduced enzyme (Tavladoraki et al, 2012).…”

“…A fine regulation of their metabolism and/or transport ensures the occurrence of the appropriate PA levels depending on the specific cell needs (Tavladoraki et al, 2012). Oxidative deamination of PAs is catalyzed by amine oxidases (AOs) in a multistep mechanism, with the release of the removed amine moiety and amino aldehydes in the oxidative phase and the production of H 2 O 2 in the reoxidation step of the reduced enzyme (Tavladoraki et al, 2012). Although AOs are a heterogenous class of enzymes varying in subcellular localization, tissue expression pattern, substrate specificity, and mode of catalysis, they share roles in both the homeostasis of PAs and the production of H 2 O 2 , the latter representing a common product in the AO-driven oxidative catabolism of PAs (Cona et al, 2006;Tavladoraki et al, 2012).…”

“…Oxidative deamination of PAs is catalyzed by amine oxidases (AOs) in a multistep mechanism, with the release of the removed amine moiety and amino aldehydes in the oxidative phase and the production of H 2 O 2 in the reoxidation step of the reduced enzyme (Tavladoraki et al, 2012). Although AOs are a heterogenous class of enzymes varying in subcellular localization, tissue expression pattern, substrate specificity, and mode of catalysis, they share roles in both the homeostasis of PAs and the production of H 2 O 2 , the latter representing a common product in the AO-driven oxidative catabolism of PAs (Cona et al, 2006;Tavladoraki et al, 2012). On the basis of the cofactor involved, AOs can be classified into two subclasses: the copper amine oxidases (CuAOs), showing high affinity for Put, and the FAD-dependent polyamine oxidases (PAOs), whose preferred substrates are Spd, Spm, and/or their acetyl derivatives (Cona et al, 2006;Tavladoraki et al, 2012).…”

Role of polyamines, their analogs and transglutaminases in biological and clinical perspectives

“…The first part of the issue starts with articles entirely devoted to polyamine catabolism and its role in animals and plants. This information could be useful in evaluating the possibility of this metabolic pathway as a target for new antiproliferative therapies in animals and stress tolerance strategies in plants (Tavladoraki et al 2011). Alterations in polyamine metabolism have been linked to a variety of disease states, most prominently to hyperproliferative diseases such as cancer (Bachrach 2004).…”