bims-polyam 2021-10-10 papers

Issue of 2021‒10‒10
five papers selected by
Sebastian J. Hofer
University of Graz

Mol Cell. 2021 Oct 07. pii: S1097-2765(21)00748-6. [Epub ahead of print]81(19): 3882-3883

Sensing spermidine through tongue-tied translation prevents too much of a good thing.

Vindu et al. (2021) identify the yeast high-affinity spermidine transporter, elucidate the mRNA uORF/eIF5a-based translational mechanism by which spermidine levels are sensed, and demonstrate that excess spermidine competitively inhibits eIF5a function, resulting in decreased spermidine uptake.

DOI: https://doi.org/10.1016/j.molcel.2021.09.014

Amino Acids. 2021 Oct 06.

Polyamine synthesis from arginine and proline in tissues of developing chickens.

Kyohei Furukawa, Wenliang He, Christopher A Bailey, Fuller W Bazer, Masaaki Toyomizu, Guoyao Wu.

Polyamines (putrescine, spermidine, and spermine) are synthesized primarily from ornithine via ornithine decarboxylase (ODC) in mammals. Although avian tissues contain ODC activity, little is known about intracellular sources of ornithine for their polyamine synthesis. This study tested the hypothesis that arginase and proline oxidase contribute to polyamine synthesis in chickens. Kidney, jejunum, leg muscle, and liver from 0-, 7-, 14- and 21-day-old broiler chickens were assayed for the activities of arginase, proline oxidase (POX), ornithine aminotransferase (OAT), and ornithine decarboxylase (ODC). Kidney slices were also used to determine 14C-polyamine synthesis from [U-14C]arginine and [U-14C]proline. Furthermore, these tissues and plasma were analyzed for polyamines. Results indicate that all tissues contained OAT (mitochondrial) and ODC (cytosolic) activities, but arginase and POX activities were only detected in the mitochondria of chicken kidneys. Renal POX and arginase activities were greater at 7 days of age compared to newly hatched birds, and declined by Day 14. Renal arginase activity was greater at 21 days compared to 14 days of age, but there was no change in renal POX activity during that same period. Concentrations of polyamines in the kidneys and plasma were greater on Day 7 compared to Day 0 and decreased thereafter on Days 14 and 21. Kidney slices readily converted arginine and proline into polyamines, with peak rates being on Day 7. Concentrations of putrescine, spermidine and spermine in the plasma of chickens were about 20- to 100-fold greater than those in mammals. Our results indicate that polyamines are synthesized from arginine and proline in avian kidneys. Unlike mammals, polyamines released from the kidneys are likely the major source of polyamines in the blood and other extra-renal tissues in chickens.

Keywords: Arginase; Chicken; Kidney; Polyamines; Proline oxidase

DOI: https://doi.org/10.1007/s00726-021-03084-7

Biotechnol Rep (Amst). 2021 Dec;32 e00674

Extremophilic bacteria restrict the growth of Macrophomina phaseolina by combined secretion of polyamines and lytic enzymes.

Ana P Santos, Luciana Nieva Muratore, Anna Solé-Gil, María E Farías, Alejandro Ferrando, Miguel A Blázquez, Carolina Belfiore.

Extremophilic microorganisms were screened as biocontrol agents against two strains of Macrophomina phaseolina (Mp02 and 06). Stenotrophomonas sp. AG3 and Exiguobacterium sp. S58 exhibited a potential in vitro antifungal effect on Mp02 growth, corresponding to 52.2% and 40.7% inhibition, respectively. This effect was confirmed by scanning electron microscopy, where images revealed marked morphological alterations in fungus hyphae. The bacteria were found to secrete lytic enzymes and polyamines. Exiguobacterium sp. S56a was the only strain able to reduce the growth of the two strains of M. phaseolina through their supernatant. Antifungal supernatant activity was correlated with the ability of bacteria to synthesize and excrete putrescine, and the exogenous application of this polyamine to the medium phenocopied the bacterial antifungal effects. We propose that the combined secretion of putrescine, spermidine, and lytic enzymes by extremophilic microorganism predispose these microorganisms to reduce the disease severity occasioned by M. phaseolina in soybean seedlings.

Keywords: Biocontrol agents; Extremophilic microorganisms; Lytic enzymes; Macrophomina phaseolina; Polyamines

DOI: https://doi.org/10.1016/j.btre.2021.e00674

Neuropsychopharmacology. 2021 Oct 07.

Fentanyl-induced hyperalgesia and analgesic tolerance in male rats: common underlying mechanisms and prevention by a polyamine deficient diet.

Emilie Laboureyras, Meric Ben Boujema, Annie Mauborgne, John Simmers, Michel Pohl, Guy Simonnet.

Opioids are a mainstay of pain management but can induce unwanted effects, including analgesic tolerance and paradoxical hyperalgesia, either of which leads to increased pain. Clinically, however, the relationship between these two phenomena remains elusive. By evaluating changes in mechanical nociceptive threshold in male rats, we found that in contrast to a purely analgesic control response to a single subcutaneous administration of fentanyl (25 μg/kg), in rats subjected to inflammatory pain 2 weeks previously (Day0), the same test dose (D13) induced a bi-phasic response: initial decreased analgesia (tolerance) followed by hyperalgesia lasting several hours. Both the tolerance and hyperalgesia were further enhanced in rats that had additionally received fentanyl on D0. The dose-response profiles (5 fg to 50 μg/kg) of pain- and opioid-experienced rats were very different from pain/drug-naive rats. At ultra-low fentanyl doses (<5 ng/kg and <500 ng/kg for naïve control and pain/drug-experienced rats, respectively), solely hyperalgesia was observed in all cases. At higher doses, which now produced analgesia alone in naive rats, reduced analgesia (tolerance) coupled with hyperalgesia occurred in pain/fentanyl-experienced rats, with both phases increasing with dose. Transcriptomic and pharmacological data revealed that an overactivation of the spinal N-methyl-D-aspartate receptor-inducible NO synthase cascade plays a critical role in both acute tolerance and hyperalgesia, and together with the finding that the magnitudes of analgesia and associated hyperalgesia are negatively correlated, is indicative of closely related phenomena. Finally, a polyamine deficient diet prevented inducible NO synthase transcript upregulation, restored fentanyl's analgesic efficacy and suppressed the emergence of hyperalgesia.

DOI: https://doi.org/10.1038/s41386-021-01200-5

J Headache Pain. 2021 Oct 06. 22(1): 117

Identification of disease- and headache-specific mediators and pathways in migraine using blood transcriptomic and metabolomic analysis.

Timea Aczél, Tamás Körtési, József Kun, Péter Urbán, Witold Bauer, Róbert Herczeg, Róbert Farkas, Krisztián Kovács, Barna Vásárhelyi, Gellért B Karvaly, Attila Gyenesei, Bernadett Tuka, János Tajti, László Vécsei, Kata Bölcskei, Zsuzsanna Helyes.

BACKGROUND: Recent data suggest that gene expression profiles of peripheral white blood cells can reflect changes in the brain. We aimed to analyze the transcriptome of peripheral blood mononuclear cells (PBMC) and changes of plasma metabolite levels of migraineurs in a self-controlled manner during and between attacks.METHODS: Twenty-four patients with migraine were recruited and blood samples were collected in a headache-free (interictal) period and during headache (ictal) to investigate disease- and headache-specific alterations. Control samples were collected from 13 age- and sex-matched healthy volunteers. RNA was isolated from PBMCs and single-end 75 bp RNA sequencing was performed using Illumina NextSeq 550 instrument followed by gene-level differential expression analysis. Functional analysis was carried out on information related to the role of genes, such as signaling pathways and biological processes. Plasma metabolomic measurement was performed with the Biocrates MxP Quant 500 Kit.
RESULTS: We identified 144 differentially-expressed genes in PBMCs between headache and headache-free samples and 163 between symptom-free patients and controls. Network analysis revealed that enriched pathways included inflammation, cytokine activity and mitochondrial dysfunction in both headache and headache-free samples compared to controls. Plasma lactate, succinate and methionine sulfoxide levels were higher in migraineurs while spermine, spermidine and aconitate were decreased during attacks.
CONCLUSIONS: It is concluded that enhanced inflammatory and immune cell activity, and oxidative stress can play a role in migraine susceptibility and headache generation.

Keywords: Cytokines; Migraine; Mitochondrial dysfunction; Peripheral blood mononuclear cells; Transcriptomic analysis

DOI: https://doi.org/10.1186/s10194-021-01285-9