bims-polyam Biomed News
on Polyamines
Issue of 2023–02–19
six papers selected by
Sebastian J. Hofer, University of Graz



  1. Cell Rep. 2023 Feb 11. pii: S2211-1247(23)00131-6. [Epub ahead of print]42(2): 112120
      Intestinal colonization of the oral bacterium Haemophilus parainfluenzae has been associated with Crohn's disease (CD) severity and progression. This study examines the role of periodontal disease (PD) as a modifier for colonization of H. parainfluenzae in patients with CD and explores the mechanisms behind H. parainfluenzae-mediated intestinal inflammation. Fifty subjects with and without CD were evaluated for the presence of PD, and their oral and fecal microbiomes were characterized. PD is associated with increased levels of H. parainfluenzae strains in subjects with CD. Oral inoculation of H. parainfluenzae elicits strain-dependent intestinal inflammation in murine models of inflammatory bowel disease, which is associated with increased intestinal interferon-γ (IFN-γ)+ CD4+ T cells and disruption of the host hypusination pathway. In summary, this study establishes a strain-specific pathogenic role of H. parainfluenzae in intestinal inflammation and highlights the potential effect of PD on intestinal colonization by pathogenic H. parainfluenzae strains in patients with CD.
    Keywords:  CP: Microbiology; Crohn’s disease; Haemophilus parainfluenzae; inflammatory bowel disease; microbiome; oral-systemic health; periodontal disease
    DOI:  https://doi.org/10.1016/j.celrep.2023.112120
  2. Biomed Chromatogr. 2023 Feb 12. e5601
      Polyamines are low molecular weight compounds and they are present in all living organisms. They are related to putrescive process, and have been studied as biomarkers for tumor progression, being analyzed in patients' biological fluids. However, polyamines can undergo degradation in serum samples, depending on storage conditions, which impairs their quantification in these matrices. Capillary electrophoresis using indirect-UV detection method has been developed and applied to evaluating the polyamines stability in human serum at different storage temperatures. Cadaverine (Cad), putrescine (Put), spermine (Spm), and spermidine (Spd) were separated in less than 4 min. The range of the correlation coefficients was 0.993-0.998. Limits of detection and quantification were respectively (in mgL-1 ): Spm: 0.209 and 0.697; Spd: 0.165 and 0.549; Put: 0.189 and 0.632; Cad: 0.125 and 0.417. Coefficient of variation (CV%) was lower than 1 % for all analytes and the recovery was 92-110 %. The method was successfully applied for polyamines spiked in human serum samples of healthy people. The results showed that the degradation of polyamines was lower in samples stored in a freezer (-20 o C).
    Keywords:  Polyamines; degradation; indirect CE-UV detection; monitoring; serum
    DOI:  https://doi.org/10.1002/bmc.5601
  3. Plant J. 2023 Feb 14.
      Polyamines such as spermidine and spermine (Spm) are essential regulators of cell growth, differentiation, maintenance of ion balance and abiotic stress tolerance. Their levels are controlled by the spermidine/spermine N1 -acetyltransferase (SSAT) via acetylation to promote either their degradation or export outside the cell as shown in mammals. Plant genomes contain at least one gene coding for SSAT, also named NATA for N-AcetylTransferase Activity. Combining kinetics, HPLC-MS and crystallography, here we show that three plant SSATs, one from the lower plant moss Physcomitrium patens and two from the higher plant Zea mays, acetylate various aliphatic polyamines and two amino acids lysine (Lys) and ornithine (Orn). Thus, plant SSATs exhibit a broad substrate specificity, unlike more specific human SSATs (hSSATs) as hSSAT1 targets polyamines whereas hSSAT2 acetylates Lys and thiaLys. The crystal structures of two PpSSAT ternary complexes, one with Lys and coenzyme A (CoA), the other with acetyl-CoA and polyethylene glycol (mimicking Spm) reveal a different binding mode for polyamine versus amino acid substrates accompanied by structural rearrangements of both the coenzyme and the enzyme. Two arginine residues, unique among plant SSATs, hold the carboxyl group of amino acid substrates. The most abundant acetylated compound accumulated in moss was N6 -acetyl-Lys whereas N5 -acetyl-Orn, known as toxic for aphids, was found in maize. Both plant species contain very low levels of acetylated polyamines. The study provides a detailed biochemical and structural basis of plant SSAT enzymes that can acetylate a wide range of substrates and likely play various roles in planta.
    Keywords:  Acetylation; N-acetyl transferase; Physcomitrium patens; X-ray crystallography; Zea mays; coenzyme A; lysine; ornithine; polyamine; spermine
    DOI:  https://doi.org/10.1111/tpj.16148
  4. Fundam Clin Pharmacol. 2023 Feb 17.
      Neuropathic pain is one of the most critical types of chronic pain despite the increasing advances in medical science. Spermidine (SPD) is a natural polyamine that has wide roles in several cellular processes inducing autophagy and reducing oxidative stress. This study aimed to investigate the effects of SPD on oxidative stress markers and pain threshold in the neuropathic rat model of chronic constriction injury (CCI) model. Eighteen adult male rats were divided into 3 groups: sham, CCI and CCI+ SPD. After induction of neuropathy via CCI model in the CCI and CCI+SPD groups, SPD (1 mg/kg/day, orally) was administered to the CCI+SPD group for 3 weeks. The behavioral tests (von Frey, hot plate) were done 4 times during the experiment. At the end of the study, electrophysiological tests, the H & E staining, and oxidative stress assay of the prefrontal cortex (PFC), spinal cord, and sciatic nerve were performed. The threshold of pain in hot plate and von Frey tests was significantly lower in the CCI group than the sham group, which was reversed by SPD treatment in the CCI+ SPD group. In addition, nerve conduction was considerably lower in the CCI group than in the sham and CCI+SPD groups (P<0.01, P< 0.05, respectively). The CCI group showed neuronal degeneration and fibrosis in the different tissues in the H & E assay; elevated tissues level of nitrite, decreased levels of SOD, GPx, and catalase were also observed. However, SPD treatment modulated the pathological changes and oxidative stress biomarkers. In conclusion, SPD showed beneficial effects in decreasing neuropathic pains. SPD treatment reduced oxidative stress, improved histopathological changes and behavioral tests in the CCI-induced neuropathic pain in in vivo model.
    Keywords:  CCI; Neuropathic pain; Oxidative stress; Spermidine
    DOI:  https://doi.org/10.1111/fcp.12880
  5. Physiol Int. 2023 Feb 17.
      We aimed to examine the effects of brain ischemia-reperfusion (IR) especially on serum parameters or liver enzymes, free radicals, cytokines, oxidatively damaged DNA, spermidine/spermine N-1-acetyltransferase (SSAT). The effects of addition of putrescine on IR will be evaluated in terms of inflammation and oxidant-antioxidant balance in liver.The study was conducted on 46 male Albino Wistar rats weighing 200-250 g. The rats were grouped into: 1-Sham group (n = 6). 2-IR group (n = 8): The carotid arteries were ligated for 30-min and reperfusion was achieved for 30-min under general anesthesia. 3-Ischemia + putrescine + reperfusion group (IPR) (n = 8): Unlike the IR group, a single dose of 250 μmol kg-1 putrescine was given by gavage at the beginning of reperfusion. In putrescine treatment groups in addition to the procedures performed in the IR group a total of 4 doses of 250 μmol kg-1 putrescine were given at 12-h intervals, with the first dose immediately after 30-min reperfusion (4-IR+putrescine group (IR+P1) (n = 8)); 3 h after the 30-min reperfusion (5-IR+putrescine group (IR+P2) (n = 8)); 6 h after the 30-min reperfusion (6-IR+putrescine group (IR+P3) (n = 8)). ALT, AST, ATP, NO, SSAT, 8-OHdG levels were analyzed in the serum, and liver samples. NF-κB and IL-6 levels were analyzed in the liver samples.Brain IR causes inflammatory, oxidative and DNA damage in the liver, and putrescine supplementation through gavage reduces liver damage by showing anti-inflammatory and antioxidant effects.
    Keywords:  8-OHdG; ATP; Brain Ischemia-Reperfusion; IL-6; NF-κB; NO; SSAT; liver; putrescine; rat
    DOI:  https://doi.org/10.1556/2060.2022.00138