bims-polyam 2022-01-30 papers

Issue of 2022‒01‒30
five papers selected by
Sebastian J. Hofer
University of Graz

World J Psychiatry. 2021 Dec 19. 11(12): 1177-1190

Polyamines and polyamine-metabolizing enzymes in schizophrenia: Current knowledge and concepts of therapy.

Hans-Gert Bernstein, Gerburg Keilhoff, Gregor Laube, Henrik Dobrowolny, Johann Steiner.

Polyamines play preeminent roles in a variety of cellular functions in the central nervous system and other organs. A large body of evidence suggests that the polyamine pathway is prominently involved in the etiology and pathology of schizophrenia. Alterations in the expression and activity of polyamine metabolizing enzymes, as well as changes in the levels of the individual polyamines, their precursors and derivatives, have been measured in schizophrenia and animal models of the disease. Additionally, neuroleptic treatment has been shown to influence polyamine concentrations in brain and blood of individuals with schizophrenia. Thus, the polyamine system may appear to be a promising target for neuropharmacological treatment of schizophrenia. However, for a number of practical reasons there is currently only limited hope for a polyamine-based schizophrenia therapy.

Keywords: Animal models; Polyamines; Schizophrenia; Spermidine; Spermine; Therapy

DOI: https://doi.org/10.5498/wjp.v11.i12.1177

Front Cell Neurosci. 2021 ;15 787319

Critical Role of Astrocytic Polyamine and GABA Metabolism in Epileptogenesis.

Zsolt Kovács, Serguei N Skatchkov, Rüdiger W Veh, Zsolt Szabó, Krisztina Németh, Pál T Szabó, Julianna Kardos, László Héja.

Accumulating evidence indicate that astrocytes are essential players of the excitatory and inhibitory signaling during normal and epileptiform activity via uptake and release of gliotransmitters, ions, and other substances. Polyamines can be regarded as gliotransmitters since they are almost exclusively stored in astrocytes and can be released by various mechanisms. The polyamine putrescine (PUT) is utilized to synthesize GABA, which can also be released from astrocytes and provide tonic inhibition on neurons. The polyamine spermine (SPM), synthesized form PUT through spermidine (SPD), is known to unblock astrocytic Cx43 gap junction channels and therefore facilitate astrocytic synchronization. In addition, SPM released from astrocytes may also modulate neuronal NMDA, AMPA, and kainate receptors. As a consequence, astrocytic polyamines possess the capability to significantly modulate epileptiform activity. In this study, we investigated different steps in polyamine metabolism and coupled GABA release to assess their potential to control seizure generation and maintenance in two different epilepsy models: the low-[Mg2+] model of temporal lobe epilepsy in vitro and in the WAG/Rij rat model of absence epilepsy in vivo. We show that SPM is a gliotransmitter that is released from astrocytes and significantly contributes to network excitation. Importantly, we found that inhibition of SPD synthesis completely prevented seizure generation in WAG/Rij rats. We hypothesize that this antiepileptic effect is attributed to the subsequent enhancement of PUT to GABA conversion in astrocytes, leading to GABA release through GAT-2/3 transporters. This interpretation is supported by the observation that antiepileptic potential of the Food and Drug Administration (FDA)-approved drug levetiracetam can be diminished by specifically blocking astrocytic GAT-2/3 with SNAP-5114, suggesting that levetiracetam exerts its effect by increasing surface expression of GAT-2/3. Our findings conclusively suggest that the major pathway through which astrocytic polyamines contribute to epileptiform activity is the production of GABA. Modulation of astrocytic polyamine levels, therefore, may serve for a more effective antiepileptic drug development in the future.

Keywords: 4-MCHA/spermidine synthase inhibitor; APCHA/spermine synthase inhibitor; WAG/Rij rat model; absence epilepsy; astrocytes; glial cells; neurons; polyamines in the central nervous system

DOI: https://doi.org/10.3389/fncel.2021.787319

Food Chem. 2022 Jan 19. pii: S0308-8146(22)00140-6. [Epub ahead of print]380 132179

Exogenous phytosulfokine α (PSKα) alleviates chilling injury of banana by modulating metabolisms of nitric oxide, polyamine, proline, and γ-aminobutyric acid.

Di Wang, Hao Huang, Yueming Jiang, Xuewu Duan, Xingyu Lin, Morteza Soleimani Aghdam, Zisheng Luo.

Chilling injury reduces the quality and commercial value of banana. The effects of exogenous phytosulfokine α (PSKα) on chilling tolerance of banana via modulating the metabolism of polyamine, proline, γ-aminobutyric acid (GABA) were studied. The results showed that the chilling injury of banana was inhibited by 150 nM PSKα treatment, which was 13.6 % lower than that of the control group at the end of storage. The activities of nitric oxide synthase (NOS), arginine decarboxylase (ADC), ornithine decarboxylase (ODC), and the endogenous NO content were increased significantly by PSKα treatment. The diamine oxidase (DAO) and polyamine oxidase (PAO) activities were inhibited, leading to putrescine (Put), spermine (Spm), and spermidine (Spd) increased. Proline and GABA contents in PSKα-treated banana were also increased, which might be due to the activated biosynthesis pathway and suppressed catabolism pathway. These results demonstrated that exogenous PSKα might be maintain quality and retard chilling injury of banana.

Keywords: Banana fruit; Cold storage; Quality; Regulated metabolism

DOI: https://doi.org/10.1016/j.foodchem.2022.132179

Front Nutr. 2021 ;8 815477

Influence of the Type of Breastfeeding and Human Milk Polyamines on Infant Anthropometric Parameters.

Nelly C Muñoz-Esparza, Edgar M Vásquez-Garibay, Elizabeth Guzmán-Mercado, Alfredo Larrosa-Haro, Oriol Comas-Basté, M Luz Latorre-Moratalla, M Teresa Veciana-Nogués, M Carmen Vidal-Carou.

Feeding choices in the early months of life are key determinants of growth during infancy. Polyamines participate in cell proliferation and differentiation, and it has also been suggested that polyamine metabolism plays a role in adipogenesis. As the main exogenous source of polyamines in the infant is human milk, the aim of this work was to study if the type of breastfeeding received and the polyamine intake from human milk has an influence on infant anthropometric parameters. A cohort of 78 full-term healthy newborns was followed up until 4 months of age; 55 were fully and 23 partially breastfed. Anthropometric measurements were taken at 2 and 4 months, when human milk samples were also collected for analysis of polyamine content by UHPLC-FL. Fully breastfed infants had a better anthropometric profile than those partially breastfed (p < 0.05). Furthermore, polyamine intake in partially breastfed infants was significantly lower compared to those fully breastfed. However, only two of the 15 anthropometric indicators evaluated (triceps skinfold and mean upper arm circumference) showed a significant inverse association with polyamine content in human milk and intake (p < 0.05). Infant growth and body composition differ according to the type of breastfeeding received. Based on the weak associations between polyamines and anthropometric indicators, it is not possible to conclude the influence of polyamines in infant growth and body composition.

Keywords: adipogenesis; full breastfeeding; infant growth; partial breastfeeding; polyamines; putrescine; spermidine; spermine

DOI: https://doi.org/10.3389/fnut.2021.815477

Cell Stress. 2022 Jan;6(1): 1-5

Rethinking the bioavailability and cellular transport properties of S-adenosylmethionine.

Yudong Sun, Jason W Locasale.

S-adenosylmethionine (SAM) is a versatile metabolite that participates in a wide range of reactions such as methylation and transsulfuration. These capabilities allow SAM to influence cellular processes such as gene expression and redox balancing. The importance of SAM is highlighted by its widespread usage as an over-the-counter nutrient supplement and as an experimental reagent in molecular biology. The bioavailability and cellular transport properties of SAM, however, are often overlooked under these contexts, putting limits on SAM's therapeutic potential and complicating the interpretation of experimental results. In this article, we examined the chemical stability and cellular permeability of SAM, proposed a schematic for indirect SAM transport across the mammalian plasma membrane, and lastly discussed the implications arising from such transport schematic.

Keywords: S-adenosyl-methionine; SAM; metabolism; methionine

DOI: https://doi.org/10.15698/cst2022.01.261