bims-polyam 2019-04-07 papers

Fish Shellfish Immunol. 2019 Apr 01. pii: S1050-4648(19)30234-7. [Epub ahead of print]

Rainbow trout (Oncorhynchus mykiss) urea cycle and polyamine synthesis gene families show dynamic expression responses to inflammation.

T Clark, J Tinsley, D J Macqueen, S A M Martin.

The urea cycle is an endogenous source of arginine that also supports removal of nitrogenous waste following protein metabolism. This cycle is considered inefficient in salmonids, where only 10-15% of nitrogenous waste is excreted as urea. In rainbow trout, arginine is an essential amino acid that has attracted attention due to its many functional roles. These roles include the regulation of protein deposition, immune responses and polyamine synthesis; the latter is directly linked to the urea cycle and involved in tissue repair. The key enzymes used in the urea cycle, namely arginase, ornithine transcarbamylase, argininosuccinate synthase and argininosuccinate lyase, in addition to two rate limiting enzymes required for polyamine synthesis (ornithine decarboxylase and s-adenosylmethionine decarboxylase) are poorly studied in fishes, and their responses to inflammation remain unknown. To address this knowledge gap, we characterised these gene families using phylogenetics and comparative genomics, investigated their mRNA distribution among a panel of tissues and established their transcriptional responses to an acute inflammatory response caused by bacterial infection in liver and muscle. Gene duplicates (paralogues) were identified for arginase (ARG1a, 1b, 2a and 2b), ornithine decarboxylase (ODC1 and 2) and s-adenosylmethionine decarboxylase (SAMdc1 and 2), including paralogues retained from an ancestral salmonid-specific whole genome duplication. ARG2a and 2b were highly upregulated following bacterial infection in liver, whereas ARG1b was downregulated, while both paralogues of SAMdc and ODC were upregulated in both liver and muscle. Overall, these findings improve our understanding of the molecules supporting the urea cycle and polyamine synthesis in fish, highlighting major changes in the regulation of these systems during inflammation.

Keywords: Arginase; Genome duplication; Immune; Polyamine; Salmonids; Urea cycle

DOI: https://doi.org/10.1016/j.fsi.2019.03.075

Metabolomics. 2019 Apr 02. 15(4): 58

Metabolomic study of polyamines in rat urine following intraperitoneal injection of γ-hydroxybutyric acid.

Hyeon-Seong Lee, Chan Seo, Young-A Kim, Meejung Park, Boyeon Choi, Moongi Ji, Sooyeun Lee, Man-Jeong Paik.

INTRODUCTION: Recently, illegal abuse of γ-hydroxybutyric acid (GHB) has increased in drug-facilitated crimes, but the determination of GHB exposure and intoxication is difficult due to rapid metabolism of GHB. Its biochemical mechanism has not been completely investigated. And a metabolomic study by polyamine profile and pattern analyses was not performed in rat urine following intraperitoneal injection with GHB.
OBJECTIVES: Urinary polyamine (PA) profiling by gas chromatography-tandem mass spectrometry was performed to monitor an altered PA according to GHB administration.
METHODS: Polyamine profiling analysis by gas chromatography-mass spectrometry combined with star pattern recognition analysis was performed in this study. The multivariate statistical analysis was used to evaluate discrimination among control and GHB administration groups.
RESULTS: Six polyamines were determined in control, single and multiple GHB administration groups. Star pattern showed distorted hexagonal shapes with characteristic and readily distinguishable patterns for each group. N1-Acetylspermine (p < 0.001), putrescine (p < 0.006), N1-acetylspermidine (p < 0.009), and spermine (p < 0.027) were significantly increased in single administration group but were significantly lower in the multiple administration group than in the control group. N1-Acetylspermine was the main polyamine for discrimination among control, single and multiple administration groups. Spermine showed similar levels in single and multiple administration groups.
CONCLUSIONS: The polyamine metabolic pattern was monitored in GHB administration groups. N1-Acetylspermine and spermine were evaluated as potential biomarkers of GHB exposure and addiction.

Keywords: Gas chromatography-mass spectrometry; Metabolomics; Multivariate analysis; Polyamine profiling analysis; Star pattern recognition analysis; γ-Hydroxybutyric acid

DOI: https://doi.org/10.1007/s11306-019-1517-2

Talanta. 2019 Jul 01. pii: S0039-9140(19)30206-1. [Epub ahead of print]199 184-188

Improved profiling of polyamines using two-dimensional gas chromatography mass spectrometry.

Zhanru Yu, Honglei Huang, Hanlin Zhang, Benedikt M Kessler.

Polyamines are a class of poly-cationic aliphatic amines, playing a role in different cellular processes such as maintaining intracellular pH and membrane potential that are relevant for general cellular physiology and ageing. The development of analytical methods for detection and quantitation of this class of compounds has been challenging due to the basic nature of these species. Both liquid chromatography (LC) and gas chromatography (GC) have been applied for separation, mostly coupled to mass spectrometry (MS) for detection. However, current methodologies suffer from lengthy extraction protocols and limitations in separation and detection levels. Here, we present a simplified and optimised method for straightforward extraction of polyamine metabolites including spermine, spermidine, norspermidine, cadaverine and putrescine from cellular and tissue material. We demonstrate that strong acid-based extraction and chemical derivatisation not only improves isolation, but also recovery. Combined with two-dimensional gas chromatography, this method provides clear separation and femtomole sensitivity for the profiling of polyamines.

Keywords: Gas chromatography; Polyamines; Putrescine 2-dimensional; Spermidine; Spermine

DOI: https://doi.org/10.1016/j.talanta.2019.02.062

Int Immunopharmacol. 2019 Mar 27. pii: S1567-5769(18)31211-6. [Epub ahead of print]71 251-258

α-Difluoromethylornithine suppresses inflammatory arthritis by impairing myeloid-derived suppressor cells.

Zhe Geng, Bingxia Ming, Shaoxian Hu, Lingli Dong, Cong Ye.

OBJECTIVES: The chemopreventive drug α-difluoromethylornithine (DFMO) has been shown to have an antinociceptive effect on mechanical allodynia in inflammatory arthritis by directly inhibiting ornithine decarboxylase (ODC) and decreasing polyamine production in inflammatory sites. However, little is known about the effect of DFMO on the immune system of inflammatory arthritis. Here, we investigated the effect of DFMO in a well-established collagen-induced arthritis (CIA) mouse model and explored its effect on the immune system.
METHODS: The effect of DFMO on the frequency of myeloid-derived suppressor cells (MDSCs) in the spleens of CIA mice and their associations with disease severity, tissue inflammation and the levels of proinflammatory T-helper (Th) 17 cells in lymphoid tissues were investigated. The effects of DFMO on disease severity and Th17 cells were compared with those of antibody depletion of MDSCs. The arthritis severity was also evaluated by adoptive transfer of MDSCs derived from DFMO- or dH2O-treated mice.
RESULTS: In this study, we showed that both MDSCs and Th17 cells were significantly expanded in CIA mice. Treatment by DFMO at the onset of CIA suppressed the development of arthritis and decreased the frequency of MDSCs and Th17 cells. MDSC depletion by anti-Gr-1 mAb achieved a similar result, while combination treatment of both methods did not achieve a significant difference compared to either of the single treatments. In addition, the adoptive transfer of MDSCs derived from dH2O-treated mice with CIA restored the arthritis severity of CIA in mice treated with anti-Gr-1 mAb, while the transfer of MDSCs from DFMO-treated mice did not have such an effect.
CONCLUSIONS: Our results identified DFMO as a potential therapeutic drug for the treatment of inflammatory arthritis.

Keywords: Collagen-induced arthritis; Myeloid-derived suppressor cells; α-Difluoromethylornithine

DOI: https://doi.org/10.1016/j.intimp.2019.03.040

J Inherit Metab Dis. 2019 Apr 01.

Challenges in diagnosing and managing adult patients with Urea Cycle Disorders.

Karolina M Stepien, Tarekegn Geberhiwot, Christian J Hendriksz, Eileen P Treacy.

Urea cycle disorders (UCD) are a group of rare inherited metabolic conditions of amino acid catabolism caused by an enzyme deficiency within the hepatic ammonia detoxification pathway. The presentation of these disorders ranges from life-threatening intoxication in the neonate to asymptomatic status in adults. Late-onset UCDs can present for the first time in adulthood and may mimic other causes of acute confusion or psychiatric diseases, and are often associated with neurological symptoms. Late-onset UCDs may become apparent during periods of metabolic stress such as rapid weight loss, gastric bypass surgery, chronic starvation or the postpartum period. Early diagnosis is critical for effective treatment and to prevent long-term complications of hyperammonaemia. The challenges of management of adults include for example: 1) poor compliance to dietary and medical treatment which can result in recurrent hospital admissions; 2) severe neurological dysfunction; 3) the management of pregnancy and the postpartum period and 4) access to multidisciplinary care peri-operatively. In this review, we highlight a number of challenges in the diagnosis and management of adult patient with late-onset UCDs and suggest a systematic management approach. This article is protected by copyright. All rights reserved.

Keywords: OTC deficiency; Urea Cycle Disorder; late-onset UCD; neurocognitive outcomes; pregnancy

DOI: https://doi.org/10.1002/jimd.12096