Polyamine catabolism and oxidative damage

Abstract

Edited by Alex Toker Polyamines (PAs) are indispensable polycations ubiquitous to all living cells. Among their many critical functions, PAs contribute to the oxidative balance of the cell. Beginning with studies by the Tabor laboratory in bacteria and yeast, the requirement for PAs as protectors against oxygen radical-mediated damage has been well established in many organisms, including mammals. However, PAs also serve as substrates for oxidation reactions that produce hydrogen peroxide (H 2 O 2) both intraand extracellularly. As intracellular concentrations of PAs can reach millimolar concentrations, the H 2 O 2 amounts produced through their catabolism, coupled with a reduction in protective PAs, are sufficient to cause the oxidative damage associated with many pathologies, including cancer. Thus, the maintenance of intracellular polyamine homeostasis may ultimately contribute to the maintenance of oxidative homeostasis. Again, pioneering studies by Tabor and colleagues led the way in first identifying spermine oxidase in Saccharomyces cerevisiae. They also first purified the extracellular bovine serum amine oxidase and elucidated the products of its oxidation of primary amine groups of PAs when included in culture medium. These investigations formed the foundation for many polyamine-related studies and experimental procedures still performed today. This Minireview will summarize key innovative studies regarding PAs and oxidative damage, starting with those from the Tabor laboratory and including the most recent advances, with a focus on mammalian systems. Polyamines (PAs) 2 are naturally occurring polycationic alkylamines that are essential for growth and survival in all mamma-lian cells (1, 2). This absolute requirement is based on the multitude of roles PAs play, many of which relate to their positive charge at physiological pH. PAs, including putrescine (Put), spermidine (Spd), and spermine (Spm) (Fig. 1), contribute to critical cellular processes such as ion channel regulation, chromatin structure maintenance, DNA replication, transcription, and translation (3-6). They also act as free radical scavengers, and their catabolism can be a source of toxic reactive oxygen species (ROS), therefore implying their potential to affect oxidative status. The main purpose of this Minireview will be to cover the salient features of PAs and their catabolism in association with oxidative stress in both normal and disease processes. Contributions of polyamines to cellular redox balance Oxidative stress occurs when ROS, such as those derived from hydrogen peroxide (H 2 O 2), exceed the physiological levels required for normal redox reactions and cell signaling. The resulting oxidative damage to macromolecules is associated with aging and a variety of related pathologies, including cancer (7, 8). PAs play dual roles in maintaining cellular oxidative homeostasis by both protecting against free radical-mediated damage and acting as substrates for enzymes that produce ROS. Polyamines as protection from oxidative damage Polyam...

The hemolymph ofBiomphalariasnail vectors of schistosomiasis supports a diverse microbiome

“…Sugar degradation is likely involved in energy generation for the bacteria. Polyamines are linked to bacterial growth and survival by reducing oxidative stress [52] which could be generated by the presence of the hemocytes [53]. Production of critical metabolites by the hemolymph microbiome could support sustainable production of these metabolites.…”

Serum polyamine metabolic profile in autoimmune thyroid disease patients

“…Polyamines, especially SPM and SPD, play important roles in regulating cellular oxidative homoeostasis. SPM and SPD can protect cells against oxidative stress damage, but their oxidation products (H 2 O 2 ) can also aggravate ROS damage . Spermidine can inhibit NF‐κB‐dependent proinflammatory cytokines and promote M2 macrophage polarization, and then autoimmune‐reactive T cells can be suppressed by these M2 macrophages .…”

“…Polyamines are biosynthesized from polyamine precursors, including S‐adenosylmethionine (SAM), L‐arginine (L‐ARG), L‐ornithine (L‐ORN) and lysine (LYS). In addition, polyamine biosynthetic and catabolic enzymes, including spermidine/spermine N1‐acetyltransferase (SSAT), ornithine decarboxylase (ODC), acetylpolyamine oxidase (APAO), S‐adenosyl‐s‐methyl decarboxylase (SAMDC) and spermine oxidase (SMO), are regulated by various factors, including oxidative stress, hormones, growth factors and inflammatory factors . Immune cells that accumulate at the site of inflammation produce proinflammatory factors and oxidative stress, which then stimulate polyamine metabolism enzymes (ODC and SSAT) by activating NF‐KB and NRF2, resulting in alterations in polyamine concentrations .…”

The plasma‐membrane polyamine transporter PUT3 is regulated by the Na+/H+ antiporter SOS1 and protein kinase SOS2

“…Therefore, the association of these three proteins could be a mechanism to mitigate oxidative stress under heat or salt stress conditions. PAs are well known to protect organisms from ROS damage, while PA catabolism generates ROS (Murray Stewart et al ., ). Thus, PA homeostasis is crucial for oxidative stress responses.…”