bims-polyam 2021-09-12 papers

bims-polyam

Biomed News

on Polyamines

Issue of 2021–09–12
seven papers selected by
Sebastian J. Hofer, University of Graz

Supramolecular imaging of spermine in cancer cells.
Deoxyhypusine synthase promotes a pro-inflammatory macrophage phenotype.
Melatonin Ameliorates Thermotolerance in Soybean Seedling through Balancing Redox Homeostasis and Modulating Antioxidant Defense, Phytohormones and Polyamines Biosynthesis.
An In-Vitro model for studies of attenuation of antibiotic-inhibited growth of Aggregatibacter actinomycetemcomitans Y4 by polyamines.
Inhibition of amyloid formation of amyloid β (1-42), amylin and insulin by 1,5-diazacyclooctanes, a spermine-acrolein conjugate.
K Deprivation Modulates the Primary Metabolites and Increases Putrescine Concentration in Brassica napus.
Relationships of Gut Microbiota Composition, Short-Chain Fatty Acids and Polyamines with the Pathological Response to Neoadjuvant Radiochemotherapy in Colorectal Cancer Patients.

Nanoscale. 2021 Sep 09.

Supramolecular imaging of spermine in cancer cells.

Han-Wen Tian, Yu-Xuan Chang, Xin-Yue Hu, Muhammad Raza Shah, Hua-Bin Li, Dong-Sheng Guo.

As an important biomarker, the overexpressed spermine has been widely investigated for cancer diagnosis and treatment. However, bioimaging of spermine in living cells is still a formidable challenge. Herein, we design a supramolecular imaging ensemble for spermine by the host-guest complexation of amphiphilic sulfonatocalix[5]arene (SC5A12C) assembly with lucigenin (LCG). Strong binding ability and complexation-induced fluorescence quenching properties enable SC5A12C to quench the fluorescence of LCG dramatically and to recover it completely due to the competition of overexpressed spermine in cancer cells. SC5A12C also exhibits excellent biocompatibility and promotes cellular uptake due to its ability to form ultra-stable assembly. Co-assembling folate further promotes the cellular uptake of folate receptor overexpressed cancer cells, contributing to enhanced bioimaging.

DOI: https://doi.org/10.1039/d1nr04328e
Cell Metab. 2021 Sep 07. pii: S1550-4131(21)00366-1. [Epub ahead of print]33(9): 1883-1893.e7

Deoxyhypusine synthase promotes a pro-inflammatory macrophage phenotype.

Emily Anderson-Baucum, Annie R Piñeros, Abhishek Kulkarni, Bobbie-Jo Webb-Robertson, Bernhard Maier, Ryan M Anderson, Wenting Wu, Sarah A Tersey, Teresa L Mastracci, Isabel Casimiro, Donalyn Scheuner, Thomas O Metz, Ernesto S Nakayasu, Carmella Evans-Molina, Raghavendra G Mirmira.

  The metabolic inflammation (meta-inflammation) of obesity is characterized by proinflammatory macrophage infiltration into adipose tissue. Catalysis by deoxyhypusine synthase (DHPS) modifies the translation factor eIF5A to generate a hypusine (Hyp) residue. Hypusinated eIF5A (eIF5AHyp) controls the translation of mRNAs involved in inflammation, but its role in meta-inflammation has not been elucidated. Levels of eIF5AHyp were found to be increased in adipose tissue macrophages from obese mice and in murine macrophages activated to a proinflammatory M1-like state. Global proteomics and transcriptomics revealed that DHPS deficiency in macrophages altered the abundance of proteins involved in NF-κB signaling, likely through translational control of their respective mRNAs. DHPS deficiency in myeloid cells of obese mice suppressed M1 macrophage accumulation in adipose tissue and improved glucose tolerance. These findings indicate that DHPS promotes the post-transcriptional regulation of a subset of mRNAs governing inflammation and chemotaxis in macrophages and contributes to a proinflammatory M1-like phenotype.

Keywords:  diabetes; hypusine; inflammation; mRNA translation; macrophage; obesity; polyamines; proteomics; transcriptomics

DOI:  https://doi.org/10.1016/j.cmet.2021.08.003
Molecules. 2021 Aug 24. pii: 5116. [Epub ahead of print]26(17):

Melatonin Ameliorates Thermotolerance in Soybean Seedling through Balancing Redox Homeostasis and Modulating Antioxidant Defense, Phytohormones and Polyamines Biosynthesis.

Muhammad Imran, Muhammad Aaqil Khan, Raheem Shahzad, Saqib Bilal, Murtaza Khan, Byung-Wook Yun, Abdul Latif Khan, In-Jung Lee.

  Global warming is impacting the growth and development of economically important but sensitive crops, such as soybean (Glycine max L.). Using pleiotropic signaling molecules, melatonin can relieve the negative effects of high temperature by enhancing plant growth and development as well as modulating the defense system against abiotic stresses. However, less is known about how melatonin regulates the phytohormones and polyamines during heat stress. Our results showed that high temperature significantly increased ROS and decreased photosynthesis efficiency in soybean plants. Conversely, pretreatment with melatonin increased plant growth and photosynthetic pigments (chl a and chl b) and reduced oxidative stress via scavenging hydrogen peroxide and superoxide and reducing the MDA and electrolyte leakage contents. The inherent stress defense responses were further strengthened by the enhanced activities of antioxidants and upregulation of the expression of ascorbate-glutathione cycle genes. Melatonin mitigates heat stress by increasing several biochemicals (phenolics, flavonoids, and proline), as well as the endogenous melatonin and polyamines (spermine, spermidine, and putrescine). Furthermore, the positive effects of melatonin treatment also correlated with a reduced abscisic acid content, down-regulation of the gmNCED3, and up-regulation of catabolic genes (CYP707A1 and CYP707A2) during heat stress. Contrarily, an increase in salicylic acid and up-regulated expression of the defense-related gene PAL2 were revealed. In addition, melatonin induced the expression of heat shock protein 90 (gmHsp90) and heat shock transcription factor (gmHsfA2), suggesting promotion of ROS detoxification via the hydrogen peroxide-mediated signaling pathway. In conclusion, exogenous melatonin improves the thermotolerance of soybean plants and enhances plant growth and development by activating antioxidant defense mechanisms, interacting with plant hormones, and reprogramming the biochemical metabolism.

Keywords:  abscisic acid; antioxidant; heat tolerance; melatonin; polyamine; salicylic acid; soybean

DOI:  https://doi.org/10.3390/molecules26175116
Mol Oral Microbiol. 2021 Sep 05.

An In-Vitro model for studies of attenuation of antibiotic-inhibited growth of Aggregatibacter actinomycetemcomitans Y4 by polyamines.

Allan Wattimena, Sukirth M Ganesan, Purnima S Kumar, Shareef M Dabdoub, John D Walters.

  Polyamines are ubiquitous polycationic molecules that are present in all prokaryotic and eukaryotic cells, and they serve as important modulators of cell growth, stress and cell proliferation. Polyamines are present at high concentrations in the periodontal pocket and could potentially affect the stress response of periodontal bacteria to antibiotics. The effects of polyamines on inhibition of growth by amoxicillin (AMX), azithromycin (AZM) and doxycycline (DOX) were investigated with the Y4 strain of Aggregatibacter actinomycetemcomitans (Aa). Bacteria were grown in brain heart infusion broth under the following conditions: 1) Aa only, 2) Aa + polyamine mix (1 mM putrescine, 0.4mM spermidine, 0.4mM spermine) 3) Aa + antibiotic, 4) Aa + antibiotic + polyamines. Growth curve analysis, MIC determination and transcriptomic studies were conducted. The presence of exogenous polyamines produced a small, but significant increase in Aa growth, and polyamines attenuated the inhibitory effects of AMX, AZM and DOX on growth. Transcriptomic analysis revealed that polyamines up-regulate expression of ribosomal biogenesis proteins and small subunits, attenuate the bacterial stress response to antibiotics, and modulate bacterial nutritional pathways in a manner that could potentially increase the virulence of Aa. In summary, the polyamine-rich environment found in periodontal pockets appears to protect Aa and reduce its susceptibility to several antimicrobial agents in this in-vitro model. This article is protected by copyright. All rights reserved.

Keywords:  Aggregatibacter.actinomycetemcomitans; amoxicillin; antimicrobial resistance; azithromycin; doxycycline; metatranscriptomic analysis

DOI:  https://doi.org/10.1111/omi.12353
Bioorg Med Chem. 2021 Aug 28. pii: S0968-0896(21)00399-0. [Epub ahead of print]46 116391

Inhibition of amyloid formation of amyloid β (1-42), amylin and insulin by 1,5-diazacyclooctanes, a spermine-acrolein conjugate.

Risako Kunitomi, Ambara R Pradipta, Haruka Kawabe, Nadine Lobsiger, Katsunori Tanaka, Tamotsu Zako.

  Amyloid aggregates of proteins are known to be involved in various diseases such as Alzheimer's disease (AD). It is therefore speculated that the inhibition of amyloid formation can play an important role in the prevention of various diseases involving amyloids. Recently, we have found that acrolein reacts with polyamines, such as spermine, and produces 1,5-diazacyclooctane, such as cyclic spermine (cSPM). cSPM could suppress the aggregation of amyloid β 1-40 (Aβ40), one of the causative proteins of AD. This result suggests the potential inhibitory effect of cSPM against Aβ 1-42 (Aβ42) and other amyloid protein aggregation which are the main pathological features of AD and other diseases. However, the effect on the aggregation of such proteins remains unclear. In this study, the effect of cSPM on the amyloid formation of Aβ42, amylin, and insulin was investigated. These three amyloidogenic proteins forming amyloids under physiological conditions (pH 7.4 and 37℃) served as model and are thought to be the causative proteins of AD, type 2 diabetes, and insulin-derived amyloidosis, respectively. Our results indicate that cSPM can suppress the amyloid aggregation of these proteins and reduce cytotoxicity. This study contributes to a better understanding of means to potentially counteract diseases by the means of polyamine and acrolein.

Keywords:  1,5-diazacyclooctane; Acrolein; Alzheimer's disease; Amylin; Amyloid fibrils; Amyloid-β; Insulin; Insulin-derived amyloidosis; Polyamine; Type 2 diabetes

DOI:  https://doi.org/10.1016/j.bmc.2021.116391
Front Plant Sci. 2021 ;12 681895

K Deprivation Modulates the Primary Metabolites and Increases Putrescine Concentration in Brassica napus.

Elise Réthoré, Lun Jing, Nusrat Ali, Jean-Claude Yvin, Sylvain Pluchon, Seyed Abdollah Hosseini.

  Potassium (K) plays a crucial role in plant growth and development and is involved in different physiological and biochemical functions in plants. Brassica napus needs higher amount of nutrients like nitrogen (N), K, phosphorus (P), sulfur (S), and boron (B) than cereal crops. Previous studies in B. napus are mainly focused on the role of N and S or combined deficiencies. Hence, little is known about the response of B. napus to K deficiency. Here, a physiological, biochemical, and molecular analysis led us to investigate the response of hydroponically grown B. napus plants to K deficiency. The results showed that B. napus was highly sensitive to the lack of K. The lower uptake and translocation of K induced BnaHAK5 expression and significantly declined the growth of B. napus after 14 days of K starvation. The lower availability of K was associated with a decrease in the concentration of both S and N and modulated the genes involved in their uptake and transport. In addition, the lack of K induced an increase in Ca2+ and Mg2+ concentration which led partially to the accumulation of positive charge. Moreover, a decrease in the level of arginine as a positively charged amino acid was observed which was correlated with a substantial increase in the polyamine, putrescine (Put). Furthermore, K deficiency induced the expression of BnaNCED3 as a key gene in abscisic acid (ABA) biosynthetic pathway which was associated with an increase in the levels of ABA. Our findings provided a better understanding of the response of B. napus to K starvation and will be useful for considering the importance of K nutrition in this crop.

Keywords:  amino acids; electric charge balance; mineral nutrition transporters; nutritional homeostasis; primary metabolites

DOI:  https://doi.org/10.3389/fpls.2021.681895
Int J Mol Sci. 2021 Sep 02. pii: 9549. [Epub ahead of print]22(17):

Relationships of Gut Microbiota Composition, Short-Chain Fatty Acids and Polyamines with the Pathological Response to Neoadjuvant Radiochemotherapy in Colorectal Cancer Patients.

Lidia Sánchez-Alcoholado, Aurora Laborda-Illanes, Ana Otero, Rafael Ordóñez, Alicia González-González, Isaac Plaza-Andrades, Bruno Ramos-Molina, Jaime Gómez-Millán, María Isabel Queipo-Ortuño.

  Emerging evidence has suggested that dysbiosis of the gut microbiota may influence the drug efficacy of colorectal cancer (CRC) patients during cancer treatment by modulating drug metabolism and the host immune response. Moreover, gut microbiota can produce metabolites that may influence tumor proliferation and therapy responsiveness. In this study we have investigated the potential contribution of the gut microbiota and microbial-derived metabolites such as short chain fatty acids and polyamines to neoadjuvant radiochemotherapy (RCT) outcome in CRC patients. First, we established a profile for healthy gut microbiota by comparing the microbial diversity and composition between CRC patients and healthy controls. Second, our metagenomic analysis revealed that the gut microbiota composition of CRC patients was relatively stable over treatment time with neoadjuvant RCT. Nevertheless, treated patients who achieved clinical benefits from RTC (responders, R) had significantly higher microbial diversity and richness compared to non-responder patients (NR). Importantly, the fecal microbiota of the R was enriched in butyrate-producing bacteria and had significantly higher levels of acetic, butyric, isobutyric, and hexanoic acids than NR. In addition, NR patients exhibited higher serum levels of spermine and acetyl polyamines (oncometabolites related to CRC) as well as zonulin (gut permeability marker), and their gut microbiota was abundant in pro-inflammatory species. Finally, we identified a baseline consortium of five bacterial species that could potentially predict CRC treatment outcome. Overall, our results suggest that the gut microbiota may have an important role in the response to cancer therapies in CRC patients.

Keywords:  SCFAs; colorectal cancer; gut microbiota; gut permeability; radiochemotherapy; treatment outcome

DOI:  https://doi.org/10.3390/ijms22179549