Biochemical and pathophysiological properties of polyamines

Amino Acids (2020) 52:111–117 https://doi.org/10.1007/s00726-020-02821-8 EDITORIAL Biochemical and pathophysiological properties of polyamines Enzo Agostinelli1,2 Received: 23 January 2020 / Accepted: 27 January 2020 / Published online: 18 February 2020 © Springer-Verlag GmbH Austria, part of Springer Nature 2020 Preface Editorial The history of polyamines dates back to the fifteenth century when spermine was discovered by Antonie van Leeuwenhoek [born in Delft, Holland (1632–1723)], but it took several decades before scientists got interested in understanding and unraveling the role(s) of spermine and other polyamines in the biology of living cells. Mammalian cells contain significant amounts of polyamines and these molecules, which are polycations, play specific roles in various tissues. Although the physiological functions of these polycations have yet to be elucidated completely at the molecular level, many studies have provided a better understanding of the roles polyamines play in cell growth, proliferation, and pathophysiological processes. At the 5th International Conference on Polyamines: Biochemical, Physiological and Clinical Perspectives held in Taiwan, in 2018, special attention has been given to the role of polyamines in carcinogenesis and in developing new approaches for cancer therapy and other diseases. The issue is a tribute and dedicated by internationally recognized experts to the memory of Professor Seymour S. Cohen, a prominent scientist in polyamine research. The manuscripts included in this special issue range from biochemistry to pharmacology, chemistry, genetics, molecular biology and clinical science on the current state of knowledge regarding the physiological, biochemical, and therapeutic actions of polyamines, and should be of use to the old and the new generation of researchers in the polyamine field. This special issue of Amino Acids brings together 17 peerreviewed manuscripts that provide the essence of the lectures and posters presented at the above-mentioned conference held in Taipei (Taiwan) in 2018 on the biological and physiological roles of polyamines. Also, a few other manuscripts are authored by international experts who were unable to attend the said conference. Short overviews of a few important concepts and notions in the subject matter are also presented; these represent tools that new investigators can benefit from in this field. The manuscripts project the role of polyamines in cell growth and differentiation, cell cycle regulation, gene expression, and signal transduction in animals, plants, and microorganisms as well as under several pathophysiological processes including carcinogenesis and other diseases. All the articles represent high-class research data obtained until the mid-2019.1 Cellular polyamine concentrations are highly regulated. Their accumulation at high extracellular concentrations or deregulation of the systems that control polyamine homeostasis can induce programmed cell death (or apoptosis) in various cell types. The polyamines spermidine and spermine are substrates for several enzymes that generate cytotoxic metabolites, via the action of monoamine oxidase (MAO), polyamine oxidase (PAO), spermine oxidase (SMOX), or copper amine oxidases (CuAOs) (Ohkubo et al. 2019; Fratini et al. 2019; Agostinelli et al. 2014). Amine oxidases (AOs) regulate the levels of these polycations. Mono-, di- and polyamines, as well as several N-acyl amines, are oxidatively 2O. deaminated by AOs in a reaction consuming O 2 and H In fact, cytotoxicity in vitro can be induced in several human tumor cell lines using purified bovine serum amino oxidase (BSAO), a CuAOs, in the presence of exogenous spermine or endogenous polyamines (Amendola et al. 2014; Agostinelli et al. 2014). It can also be achieved via the injection of the enzyme into the tumor in vivo (Averill-Bates et al. 2005). Amine oxidases preferentially use polyamines (spermine and Handling Editor: E. Closs. * Enzo Agostinelli ; 1 Department of Biochemical Sciences, A. Rossi Fanelli’, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy 2 International Polyamines Foundation ‘ETS-ONLUS’, Via del Forte Tiburtino 98, 00159 Rome, Italy 1 All manuscripts in this special issue were subjected to external peer reviewing according to the policy of this journal. 13 Vol.:(0123456789) 112 spermidine) as substrate to generate the reactive oxygen species (ROS), H2O2, and aldehyde(s). Spermidine and spermine exist in cells as an RNA–polyamine complex to regulate protein synthesis (Igarashi and Kashiwagi 2015). When cells are damaged, polyamines are released from RNA, especially from ribosomes, and acrolein is produced by spermine oxidase, one of the polyamine-metabolizing enzymes (Pegg 2013). Interestingly, recent research has shown that phytohormones affect polyamine metabolism/homeostasis via impact on polyamine biosynthesis and catabolic genes (Anwar et al. 2015). Also, it seems apparent that in plants polyamines can interact with nitrous oxide (NO) and H2O2 to program cellular senescence (Mattoo and SobieszczukNowicka 2018). In this issue, it is reaffirmed (Igarashi et al. 2020) that acrolein ( CH 2=CH–CHO) produced from spermine is more toxic than reactive oxygen species ( O2−·, H2O2 and · OH) (Igarashi et al. 2018). The authors also correlate several diseases with acrolein. In brain infarction and dementia, incipient patients with high sensitivity and specificity were identified by measuring protein-conjugated acrolein (PC-Acro) in plasma, together with IL-6 and CRP in brain infarction and Aβ40/42 in dementia. The level of PC-Acro in plasma and saliva also correlated with the seriousness of renal failure and Sjӧgren’s syndrome, respectively. Thus, scavenging acrolein is of great importance in maintaining the QOL (quality of life) of the elderly. Polyamines are often present at high concentrations in growing tissues as well as in the rapidly dividing tumor cells and likely activate hyperproliferative diseases such as various cancer cells. Therefore, special attention has been paid to their involvement in carcinogenesis and in developing new approaches to cancer therapy and other diseases. Amine oxidases (AOs) regulate the levels of polyamines and generate cytotoxic metabolites (Ohkubo et al. 2019; Agostinelli et al. 2014). Interestingly, spermine oxidase (SMOX), a FAD-containing enzyme, specifically oxidizes spermine (Spm) and its dysregulation alters polyamine homeostasis, leading to aetiology of several pathological conditions, including cancer (Casero and Pegg 2010). Direct mechanistic links between inflammation, SMOX activity, ROS production, and carcinogenesis have been demonstrated (Goodwin et al. 2008; Fratini et al. 2019). Main biochemical, cellular, and physiological processes in which SMOX is involved have been highlighted (Cervelli et al. 2012). In the last decade, a number of studies have demonstrated that polyamine metabolism is de (...truncated)