bims-polyam 2020-07-12 papers

on Polyamines

Issue of 2020–07–12
nine papers selected by
Sebastian J. Hofer, University of Graz and Alexander Ivanov, Engelhardt Institute of Molecular Biology

Nutritional Aspects of Spermidine.
Spermidine Intake is Associated with Cortical Thickness and Hippocampal Volume in Older Adults.
Metabolic signature of eyelid basal cell carcinoma.
Spermidine activates RIP1 deubiquitination to inhibit TNF-α-induced NF-κB/p65 signaling pathway in osteoarthritis.
Metabolic engineering of Escherichia coli for agmatine production.
Protective Effects of Spermidine and Melatonin on Deltamethrin-Induced Cardiotoxicity and Neurotoxicity in Zebrafish.
Influence of spermine and nitrogen deficiency on growth and secondary metabolites accumulation in Castilleja tenuiflora Benth. cultured in a RITA® temporary immersion system.
Metabolome Changes in Cerebral Ischemia.
Identification and characterization of differentially expressed genes in the rice root following exogenous application of spermidine during salt stress.

Annu Rev Nutr. 2020 Jul 07.

Nutritional Aspects of Spermidine.

Frank Madeo, Sebastian J Hofer, Tobias Pendl, Maria A Bauer, Tobias Eisenberg, Didac Carmona-Gutierrez, Guido Kroemer.

Natural polyamines (spermidine and spermine) are small, positively charged molecules that are ubiquitously found within organisms and cells. They exert numerous (intra)cellular functions and have been implicated to protect against several age-related diseases. Although polyamine levels decline in a complex age-dependent, tissue-, and cell type-specific manner, they are maintained in healthy nonagenarians and centenarians. Increased polyamine levels, including through enhanced dietary intake, have been consistently linked to improved health and reduced overall mortality. In preclinical models, dietary supplementation with spermidine prolongs life span and health span. In this review, we highlight salient aspects of nutritional polyamine intake and summarize the current knowledge of organismal and cellular uptake and distribution of dietary (and gastrointestinal) polyamines and their impact on human health. We further summarize clinical and epidemiological studies of dietary polyamines. Please see http://www.annualreviews.org/page/journal/pubdates for expected final online publication date for the Annual Review of Nutrition, Volume 40. 2020.

DOI: https://doi.org/10.1146/annurev-nutr-120419-015419
Neuroimage. 2020 Jul 03. pii: S1053-8119(20)30618-2. [Epub ahead of print] 117132

Spermidine Intake is Associated with Cortical Thickness and Hippocampal Volume in Older Adults.

Claudia Schwarz, Nora Horn, Gloria Benson, Isabel Wrachtrup Calzado, Katharina Wurdack, Raimund Pechlaner, Ulrike Grittner, Miranka Wirth, Agnes Flöel.

   BACKGROUND: The natural polyamine spermidine, known to be important for cellular function, decreases during aging. Previous research has demonstrated beneficial impact of spermidine intake on memory functions in both animal models and humans, suggesting that spermidine may be a preventive approach to delay age-related cognitive decline and possibly even Alzheimer's disease (AD). However, the association of spermidine intake with brain health in humans is still unknown. In this study, we aimed to determine the association between dietary spermidine intake and structural brain measures in older individuals with subjective cognitive decline (SCD) and healthy controls (HC).
METHODS: Dietary spermidine intake and adherence to Mediterranean Diet (MeDi) were assessed by a self-reported food frequency questionnaire in 90 older adults with SCD and 47 HC. Processing of structural MRI data yielded global brain volumes, hippocampal volume, mean and regional cortical thickness, and cortical thickness in a template encompassing AD-vulnerable regions. In exploratory analyses, the association between spermidine intake and structural brain measures was assessed using adjusted and unadjusted linear regression models. Additionally, we tested for differential associations as a function of group. Mediation analyses were performed to examine whether dietary spermidine intake mediates the associations between adherence to MeDi and structural brain measures.
RESULTS: Higher spermidine intake was associated with larger hippocampal volume (standardized β=0.262, p=0.002), greater mean cortical thickness (standardized β=0.187, p=0.031), and greater cortical thickness in AD-vulnerable brain regions (standardized β=0.176, p=0.042), the parietal (standardized β=0.202, p=0.020), and temporal lobes (standardized β=0.217, p=0.012). No significant differential effect emerged between older adults with SCD and HC. Moreover, a substantial mediating effect of dietary spermidine intake on the associations between adherence to MeDi and structural brain measures was observed.
CONCLUSION: Higher dietary spermidine intake was positively associated with several structural brain measures, irrespective of the presence of SCD, and substantially mediated the relationship of adherence to MeDi and structural brain measures. Our data suggest that higher spermidine intake might be a promising dietary approach to preserve brain health in older adults, a hypothesis currently tested in an interventional trial.

Keywords:  Cortical Thickness; Hippocampal Volume; Mediterranean Diet; Spermidine; Subjective Cognitive Decline

DOI:  https://doi.org/10.1016/j.neuroimage.2020.117132
Exp Eye Res. 2020 Jul 07. pii: S0014-4835(20)30398-5. [Epub ahead of print] 108140

Metabolic signature of eyelid basal cell carcinoma.

Jiancheng Huang, Jamie Schaefer, Yekai Wang, Lauren Gioia, Ying Pei, Xiaofei Shi, Shanawar Waris, Chen Zhao, John Nguyen, Jianhai Du.

   PURPOSE: Eyelid basal cell carcinoma (BCC) is the most common eyelid malignancy. Metabolic reprogramming is critical in tumorigenesis, but the metabolic feature of eyelid BCC remains elusive. In this study, we aim to reveal the metabolic profile in eyelid BCC using targeted metabolomics. Eyelid samples were collected from patients who had removal of BCC and from control patients who underwent blepharoplasty. Multivariate analysis of metabolomics data distinguished the two groups, indicating that eyelid BCC has significantly different metabolome than the healthy tissue. We found 16 increased and 11 decreased metabolites in the BCC tissues. These metabolites were highly enriched in the metabolism of nicotinamide adenine dinucleotide (NAD), glutathione metabolism, polyamine metabolism, and the metabolism of glycine, serine, threonine, arginine and proline. amino acid metabolism. Metabolites from NAD metabolism (Nicotinamide; Nicotinamide riboside; N1-Methylnicotinamide) had the highest sensitivity, specificity, and prediction accuracy in a prediction model for eyelid BCC. In conclusion, eyelid BCC has a signature change of cell metabolome. Metabolites in NAD metabolic pathways could potentially be biomarkers or therapeutic targets for eyelid BCC.

Keywords:  Eyelid basal cell carcinoma; LC-MS/MS; Metabolism

DOI:  https://doi.org/10.1016/j.exer.2020.108140
Cell Death Dis. 2020 Jul 06. 11(7): 503

Spermidine activates RIP1 deubiquitination to inhibit TNF-α-induced NF-κB/p65 signaling pathway in osteoarthritis.

Zhong Chen, Chuang-Xin Lin, Bin Song, Chang-Chuan Li, Jun-Xiong Qiu, Shi-Xun Li, Si-Peng Lin, Wen-Qiang Luo, Yuan Fu, Gui-Bin Fang, Li Wei-Ping, Phei Er Saw, Yue Ding.

Spermidine has been known to inhibit the production of pro-inflammatory cytokines. However, there are no reports about anti-inflammatory effects of spermidine on osteoarthritis (OA). Herein, we examined whether OA progression could be delayed by intraperitoneal injection (i.p.) of spermidine in the anterior cruciate ligament transection (ACLT) and TNF-α induced arthritis (TIA) mouse models. During the process, human FLS cells (H-FLS) were used to investigate the potential ubiquitination mechanism of spermidine-mediated RIP1 in TNF-α-induced NF-κB/p65 signaling. We found that spermidine attenuated synovitis, cartilage degeneration and osteophyte formation, resulting in substantially lower OARSI scores and TNF-α scores in spermidine-treated ACLT and TIA mice. In terms of the mechanism, 9 μM spermidine did not affect the viability, proliferation, cell cycle and apoptosis of H-FLS, and exerted inhibitory effects by activating CYLD-mediated RIP1 deubiquitination on TNF-α-induced NF-κB/p65 signaling in H-FLS. From these data, we can conclude that spermidine attenuates OA progression by the inhibition of TNF-α-induced NF-κB pathway via the deubiquitination of RIP1 in FLS. Therefore, intake of spermidine could be a potential therapy for preventing OA.

DOI: https://doi.org/10.1038/s41419-020-2710-y
Eng Life Sci. 2019 Jan;19(1): 13-20

Metabolic engineering of Escherichia coli for agmatine production.

Daqing Xu, Lirong Zhang.

  Agmatine is a kind of important biogenic amine. The chemical synthesis route is not a desirable choice for industrial production of agmatine. To date, there are no reports on the fermentative production of agmatine by microorganism. In this study, the base Escherichia coli strain AUX4 (JM109 ∆speC ∆speF ∆speB ∆argR) capable of excreting agmatine into the culture medium was first constructed by sequential deletions of the speC and speF genes encoding the ornithine decarboxylase isoenzymes, the speB gene encoding agmatine ureohydrolase and the regulation gene argR responsible for the negative control of the arg regulon. The speA gene encoding arginine decarboxylase harboured by the pKK223-3 plasmid was overexpressed in AUX4, resulting in the engineered strain AUX5. The batch and fed-batch fermentations of the AUX5 strain were conducted in a 3-L bioreactor, and the results showed that the AUX5 strain was able to produce 1.13 g agmatine L-1 with the yield of 0.11 g agmatine g-1 glucose in the batch fermentation and the fed-batch fermentation of AUX5 allowed the production of 15.32 g agmatine L-1 with the productivity of 0.48 g agmatine L-1 h-1, demonstrating the potential of E. coli as an industrial producer of agmatine.

Keywords:  Agmatine production; Batch and fed‐batch fermentations; Escherichia coli; Gene deletion; Gene overexpression

DOI:  https://doi.org/10.1002/elsc.201800104
Cardiovasc Toxicol. 2020 Jul 10.

Protective Effects of Spermidine and Melatonin on Deltamethrin-Induced Cardiotoxicity and Neurotoxicity in Zebrafish.

Xingyu Liu, Qian Gao, Zeyang Feng, Yaqiu Tang, Xin Zhao, Dongyan Chen, Xizeng Feng.

  Increased application of the pyrethroid insecticide deltamethrin has adverse effects on the cardiac system and neurobehavior on the non-target organisms, which has raised the public's attention. Because of spermidine and melatonin considered to have cardioprotective and neuroprotective characteristics, zebrafish were utilized as the model organism to explore the protective effects of spermidine and melatonin against deltamethrin-induced toxicity. We tested the neurobehavior of zebrafish larvae through a rest/wake behavior assay, and evaluated the levels of the expression of Scn5lab, gata4, nkx2.5, hcrt, hcrtr, and aanat2 by qRT-PCR. Besides that cmlc2 was evaluated by whole-mount in situ hybridization. Results have shown that compared with control group, 0.025 mg/L deltamethrin could significantly disturb the cardiac development, downregulating the expression of Scn5lab and transcriptional factors gata4 and nkx2.5, disturbing cardiac looping, resulting in defects in cardiac morphology and function. Moreover, deltamethrin could alter the expression levels of rest/wake genes and cause hyperactivity in zebrafish larvae. Besides, compared with deltamethrin group, the exogenous 0.01 mg/L spermidine and 0.232 mg/L melatonin could significantly rescue the adverse effects of deltamethrin on the cardiac system and neurobehavior in zebrafish. This indicated that spermidine and melatonin have neuroprotective and cardioprotective effects against deltamethrin-induced adverse effects in zebrafish.

Keywords:  Cardiotoxicity; Deltamethrin; Melatonin; Spermidine; Zebrafish

DOI:  https://doi.org/10.1007/s12012-020-09591-5
Eng Life Sci. 2019 Dec;19(12): 944-954

Influence of spermine and nitrogen deficiency on growth and secondary metabolites accumulation in Castilleja tenuiflora Benth. cultured in a RITA® temporary immersion system.

Elizabeth Rubio-Rodríguez, Alma Rosa López-Laredo, Virginia Medina-Pérez, Gabriela Trejo-Tapia, José Luis Trejo-Espino.

  The effect of exogenous spermine (SPM) on Castilleja tenuiflora shoots developing under nitrogen deficiency (ND) stress was evaluated. Shoots cultivated in a temporary immersion system were subjected to four experimental treatments: (1) control; (2) exogenous SPM; (3) ND; and (4) ND+SPM. Shoots were longer in the ND+SPM treatment (6.3 ± 0.5 cm) than in the ND treatment (4.2 ± 0.5 cm). The total chlorophyll content was similar in the control and SPM treatments (0.41 µg mg-1 FM) and the highest values of total phenolic content were detected at 21 days in the ND+SPM treatment (84.1 ± 0.05 GAE g-1 DM). In the ND+SPM treatment, the phenylalanine ammonia lyase activity increased earlier than in ND treatment, and reached its maximum at day 21 (3.9 ± 0.2 µmol E-CIN h-1 mg-1 protein). Compared with the control, the ND and ND+SPM treatments resulted in increased secondary metabolites contents in both root and aerial parts. The strongest effect was in the roots, where the SPM and ND+SPM treatments both resulted in increased quercetin content (4.3-fold that in the control). Our results showed that SPM partially counteract the damage caused by ND and results in increased contents of valuable bioactive compounds.

Keywords:  nitrogen deficiency; polyamine; secondary metabolism; spermine; temporary immersion system

DOI:  https://doi.org/10.1002/elsc.201900040
Cells. 2020 Jul 07. pii: E1630. [Epub ahead of print]9(7):

Metabolome Changes in Cerebral Ischemia.

Tae Hwan Shin, Da Yeon Lee, Shaherin Basith, Balachandran Manavalan, Man Jeong Paik, Igor Rybinnik, M Maral Mouradian, Jung Hwan Ahn, Gwang Lee.

  Cerebral ischemia is caused by perturbations in blood flow to the brain that trigger sequential and complex metabolic and cellular pathologies. This leads to brain tissue damage, including neuronal cell death and cerebral infarction, manifesting clinically as ischemic stroke, which is the cause of considerable morbidity and mortality worldwide. To analyze the underlying biological mechanisms and identify potential biomarkers of ischemic stroke, various in vitro and in vivo experimental models have been established investigating different molecular aspects, such as genes, microRNAs, and proteins. Yet, the metabolic and cellular pathologies of ischemic brain injury remain not fully elucidated, and the relationships among various pathological mechanisms are difficult to establish due to the heterogeneity and complexity of the disease. Metabolome-based techniques can provide clues about the cellular pathologic status of a condition as metabolic disturbances can represent an endpoint in biological phenomena. A number of investigations have analyzed metabolic changes in samples from cerebral ischemia patients and from various in vivo and in vitro models. We previously analyzed levels of amino acids and organic acids, as well as polyamine distribution in an in vivo rat model, and identified relationships between metabolic changes and cellular functions through bioinformatics tools. This review focuses on the metabolic and cellular changes in cerebral ischemia that offer a deeper understanding of the pathology underlying ischemic strokes and contribute to the development of new diagnostic and therapeutic approaches.

Keywords:  cerebral ischemia; metabolic network; metabolomics; middle cerebral artery occlusion; oxygen-glucose deprivation

DOI:  https://doi.org/10.3390/cells9071630
Genomics. 2020 Jul 07. pii: S0888-7543(19)30031-X. [Epub ahead of print]

Identification and characterization of differentially expressed genes in the rice root following exogenous application of spermidine during salt stress.

Jayita Saha, Kalyan Giri, Sudipta Roy.

  Salinity is a major limiting factor in crop production. Exogenous spermidine (spd) effectively ameliorates salt injury, though the underlying molecular mechanism is poorly understood. We have used a suppression subtractive hybridization method to construct a cDNA library that has identified up-regulated genes from rice root under the treatment of spd and salt. Total 175 high-quality ESTs of about 100-500 bp in length with an average size of 200 bp are isolated, clustered and assembled into a collection of 62 unigenes. Gene ontology analysis using the KEGG pathway annotation database has classified the unigenes into 5 main functional categories and 13 subcategories. The transcripts abundance has been validated using Real-Time PCR. We have observed seven different types of post-translational modifications in the DEPs. 44 transmembrane helixes are predicted in 6 DEPs. This above information can be used as first-hand data for dissecting the administrative role of spd during salinity.

Keywords:  Differentially expressed genes; Indica rice; Real-time PCR; Salt stress; Spermidine; Suppression subtractive hybridization

DOI:  https://doi.org/10.1016/j.ygeno.2020.07.011