bims-polyam 2021-11-14 papers

bims-polyam

Biomed News

on Polyamines

Issue of 2021–11–14
fiveteen papers selected by
Sebastian J. Hofer, University of Graz

Polyamine Metabolism under Different Light Regimes in Wheat.
Dietary supplementation with L-arginine between days 14 and 25 of gestation enhances NO and polyamine syntheses and the expression of angiogenic proteins in porcine placentae.
The critical role of the aldehyde dehydrogenase PauC in spermine, spermidine, and diaminopropane toxicity in Pseudomonas aeruginosa: Its possible use as a drug target.
Polyamines Upregulate Cephalosporin C Production and Expression of β-Lactam Biosynthetic Genes in High-Yielding Acremonium chrysogenum Strain.
Protective Role of Spermidine in Colitis and Colon Carcinogenesis.
TOR senses and regulates spermidine metabolism during seedling establishment and growth in maize and Arabidopsis.
Recent Advances in the Synthesis of Polyamine Derivatives and Their Applications.
Polyamine metabolism links gut microbiota and testicular dysfunction.
Total ginsenosides promote the IEC-6 cell proliferation via affecting the regulatory mechanism mediated by polyamines.
Improving water deficit tolerance of Salvia officinalis L. using putrescine.
Red Blood Cell Metabolism in Pyruvate Kinase Deficient Patients.
Emergence of cationic polyamine dendrimersomes: design, stimuli sensitivity and potential biomedical applications.
Calcium-sensing receptor protects intestinal integrity and alleviates the inflammatory response via the Rac1/PLCγ1 signaling pathway.
Snyder-Robinson syndrome: differential diagnosis of osteogenesis imperfecta.
First reported case of pregnancy in a patient with ornithine aminotransferase deficiency.

Int J Mol Sci. 2021 Oct 29. pii: 11717. [Epub ahead of print]22(21):

Polyamine Metabolism under Different Light Regimes in Wheat.

Orsolya Kinga Gondor, Judit Tajti, Kamirán Áron Hamow, Imre Majláth, Gabriella Szalai, Tibor Janda, Magda Pál.

  Although the relationship between polyamines and photosynthesis has been investigated at several levels, the main aim of this experiment was to test light-intensity-dependent influence of polyamine metabolism with or without exogenous polyamines. First, the effect of the duration of the daily illumination, then the effects of different light intensities (50, 250, and 500 μmol m-2 s-1) on the polyamine metabolism at metabolite and gene expression levels were investigated. In the second experiment, polyamine treatments, namely putrescine, spermidine and spermine, were also applied. The different light quantities induced different changes in the polyamine metabolism. In the leaves, light distinctly induced the putrescine level and reduced the 1,3-diaminopropane content. Leaves and roots responded differently to the polyamine treatments. Polyamines improved photosynthesis under lower light conditions. Exogenous polyamine treatments influenced the polyamine metabolism differently under individual light regimes. The fine-tuning of the synthesis, back-conversion and terminal catabolism could be responsible for the observed different polyamine metabolism-modulating strategies, leading to successful adaptation to different light conditions.

Keywords:  light intensity; plant hormones; polyamines; putrescine; spermidine; spermine; wheat

DOI:  https://doi.org/10.3390/ijms222111717
Amino Acids. 2021 Nov 06.

Dietary supplementation with L-arginine between days 14 and 25 of gestation enhances NO and polyamine syntheses and the expression of angiogenic proteins in porcine placentae.

Mohammed A Elmetwally, Xilong Li, Gregory A Johnson, Robert C Burghardt, Cassandra M Herring, Avery C Kramer, Cynthia J Meininger, Fuller W Bazer, Guoyao Wu.

  Dietary supplementation with 0.4 or 0.8% L-arginine (Arg) to gilts between days 14 and 25 of gestation enhances embryonic survival and vascular development in placentae; however, the underlying mechanisms are largely unknown. This study tested the hypothesis that Arg supplementation stimulated placental expression of mRNAs and proteins that enhance angiogenesis, including endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), placental growth factor (PGF), GTP cyclohydrolase-I (GTP-CH1), ornithine decarboxylase (ODC1), and vascular endothelial growth factor receptors 1 and 2 (VEGFR1 and VEGFR2). Beginning on the day of breeding, gilts were fed daily 2 kg of a corn-soybean meal-based diet supplemented with 0.0 (control), 0.4, or 0.8% Arg. On day 25 of gestation, gilts were hysterectomized to obtain uteri and conceptuses for histochemical and biochemical analyses. eNOS and VEGFR1 proteins were localized to endothelial cells of maternal uterine blood vessels and to the uterine luminal epithelium, respectively. Compared with the control, dietary supplementation with 0.4 or 0.8% Arg increased (P < 0.05) the amounts of nitrite plus nitrate (NOx; oxidation products of NO) and polyamines in allantoic and amniotic fluids, concentrations of NOx, tetrahydrobiopterin (BH4, an essential cofactor for all NOS isoforms) and polyamines in placentae, as well as placental protein abundances of GTP-CH1 (the key enzyme for BH4 production) and ODC1 (the key enzyme for polyamine synthesis). Placental mRNA levels for GTP-CH1, eNOS, PGF, VEGF, and VEGFR2 increased in response to both 0.4% and 0.8% Arg supplementation. Collectively, these results indicate that dietary Arg supplementation to gilts between days 14 and 25 of pregnancy promotes placental angiogenesis by increasing the expression of mRNAs and proteins for angiogenic factors as well as NO and polyamine syntheses.

Keywords:  Angiogenesis; Arginine; Nitric oxide; Placenta; Polyamines; Vascular endothelial growth factor

DOI:  https://doi.org/10.1007/s00726-021-03097-2
FEBS J. 2021 Nov 12.

The critical role of the aldehyde dehydrogenase PauC in spermine, spermidine, and diaminopropane toxicity in Pseudomonas aeruginosa: Its possible use as a drug target.

Yudy V Cardona-Cardona, Ignacio Regla, Javier Andrés Juárez-Díaz, Javier Carrillo-Campos, Manuel López-Ortiz, Alejandro Aguilera-Cruz, Carlos Mújica-Jiménez, Rosario A Muñoz-Clares.

  The opportunistic human pathogen Pseudomonas aeruginosa exhibits great resistance to antibiotics so new therapeutic agents are urgently needed. Since polyamines levels are incremented in infected tissues, we explored whether the formation of a toxic aldehyde in polyamines degradation can be exploited in combating infection. We cloned the gene encoding the only aminoaldehyde dehydrogenase involved in P. aeruginosa polyamines-degradation routes, PaPauC, overexpressed this enzyme, and found that it oxidizes 3-aminopropionaldehyde (APAL) and 3-glutamyl-3-aminopropionaldehyde (GluAPAL)-produced in spermine (Spm), spermidine (Spd), and diaminopropane (Dap) degradation-, as well as 4-aminobutyraldehyde (ABAL) and 4-glutamyl-4-aminobutyraldehyde (GluABAL)-formed in putrescine (Put) degradation. As the catalytic efficiency of PaPauC with APAL was 30-times lower than with GluAPAL, and GluAPAL is predominantly formed, APAL will be poorly oxidized "in vivo". We found polyamines-induced increases in the PaPauC activity of cell crude-extracts and in the expression of the PapauC gene that were diminished by glucose. Spm, Spd, or Dap, but not Put, were toxic to P. aeruginosa even in presence of other carbon and nitrogen sources, particularly to a strain with the PapauC gene disrupted. APAL, but not GluAPAL, was highly toxic even to wild-type cells, suggesting that its accumulation, particularly in the absence of, or low, PaPauC activity is responsible for the toxicity of Spm, Spd, and Dap. Our results shed light on the toxicity mechanism of these three polyamines and strongly support the critical role of PaPauC in this toxicity. Thus, PaPauC emerges as a novel potential drug target whose inhibition might help in combating infection by this important pathogen.

Keywords:  3-aminopropionaldehyde toxicity; bacterial growth inhibition; enzyme inhibition; polyamines degradation; substrate specificity

DOI:  https://doi.org/10.1111/febs.16277
Molecules. 2021 Nov 02. pii: 6636. [Epub ahead of print]26(21):

Polyamines Upregulate Cephalosporin C Production and Expression of β-Lactam Biosynthetic Genes in High-Yielding Acremonium chrysogenum Strain.

Alexander A Zhgun, Mikhail A Eldarov.

  The high-yielding production of pharmaceutically significant secondary metabolites in filamentous fungi is obtained by random mutagenesis; such changes may be associated with shifts in the metabolism of polyamines. We have previously shown that, in the Acremonium chrysogenum cephalosporin C high-yielding strain (HY), the content of endogenous polyamines increased by four- to five-fold. Other studies have shown that the addition of exogenous polyamines can increase the production of target secondary metabolites in highly active fungal producers, in particular, increase the biosynthesis of β-lactams in the Penicillium chrysogenum Wis 54-1255 strain, an improved producer of penicillin G. In the current study, we demonstrate that the introduction of exogenous polyamines, such as spermidine or 1,3-diaminopropane, to A. chrysogenum wild-type (WT) and HY strains, leads to an increase in colony germination and morphological changes in a complete agar medium. The addition of 5 mM polyamines during fermentation increases the production of cephalosporin C in the A. chrysogenum HY strain by 15-20% and upregulates genes belonging to the beta-lactam biosynthetic cluster. The data obtained indicate the intersection of the metabolisms of polyamines and beta-lactams in A. chrysogenum and are important for the construction of improved producers of secondary metabolites in filamentous fungi.

Keywords:  Acremonium chrysogenum; biosynthesis of secondary metabolites; cephalosporin C; filamentous fungi; polyamines

DOI:  https://doi.org/10.3390/molecules26216636
Gastroenterology. 2021 Nov 09. pii: S0016-5085(21)03727-6. [Epub ahead of print]

Protective Role of Spermidine in Colitis and Colon Carcinogenesis.

Alain P Gobert, Yvonne L Latour, Mohammad Asim, Daniel P Barry, Margaret M Allaman, Jordan L Finley, Thaddeus M Smith, Kara M McNamara, Kshipra Singh, Johanna C Sierra, Paula B Luis, Claus Schneider, M Kay Washington, M Blanca Piazuelo, Shilin Zhao, Lori A Coburn, Keith T Wilson.

   BACKGROUND & AIMS: Because inflammatory bowel disease is increasing worldwide and can lead to colitis-associated carcinoma (CAC), new interventions are needed. We have shown that spermine oxidase (SMOX), which generates spermidine (Spd), regulates colitis. Here we determined if Spd treatment reduces colitis and carcinogenesis.
METHODS: SMOX was quantified in human colitis and associated dysplasia using RT-qPCR and immunohistochemistry. We used wild-type (WT) and Smox-/- C57BL/6 mice treated with dextran sulfate sodium (DSS) or azoxymethane (AOM)-DSS as models of colitis and CAC, respectively. Mice with epithelial-specific deletion of Apc were used as a model of sporadic colon cancer. Animals were supplemented or not with Spd in the drinking water. Colonic polyamines, inflammation, tumorigenesis, transcriptomes, and microbiomes were assessed.
RESULTS: SMOX mRNA levels were decreased in human ulcerative colitis tissues and inversely correlated with disease activity, and SMOX protein was reduced in colitis-associated dysplasia. DSS colitis and AOM-DSS-induced dysplasia and tumorigenesis were worsened in Smox-/- versus WT mice and improved in both genotypes with Spd. Tumor development caused by Apc deletion was also reduced by Spd. Smox deletion and AOM-DSS treatment were both strongly associated with increased expression of alpha-defensins, which was reduced by Spd. A shift in the microbiome, with reduced abundance of Prevotella and increased Proteobacteria and Deferribacteres, occurred in Smox-/- mice and was reversed with Spd.
CONCLUSIONS: Loss of SMOX is associated with exacerbated colitis and CAC, increased alpha-defensin expression, and dysbiosis of the microbiome. Spd supplementation reverses these phenotypes, indicating that it has potential as an adjunctive treatment for colitis and chemopreventive for colon carcinogenesis.

Keywords:  Alpha-defensins; Chemoprevention; Colitis-associated carcinogenesis; Inflammatory bowel disease; Intestinal microbiota; Polyamines; Spermidine

DOI:  https://doi.org/10.1053/j.gastro.2021.11.005
iScience. 2021 Nov 19. 24(11): 103260

TOR senses and regulates spermidine metabolism during seedling establishment and growth in maize and Arabidopsis.

Kenia Salazar-Díaz, Yihan Dong, Csaba Papdi, Ernesto Miguel Ferruzca-Rubio, Grecia Olea-Badillo, Lyubov A Ryabova, Tzvetanka D Dinkova.

  Spermidine (Spd) is a nitrogen sink and signaling molecule that plays pivotal roles in eukaryotic cell growth and must be finetuned to meet various energy demands. In eukaryotes, target of rapamycin (TOR) is a central nutrient sensor, especially N, and a master-regulator of growth and development. Here, we discovered that Spd stimulates the growth of maize and Arabidopsis seedlings through TOR signaling. Inhibition of Spd biosynthesis led to TOR inactivation and growth defects. Furthermore, disruption of a TOR complex partner RAPTOR1B abolished seedling growth stimulation by Spd. Strikingly, TOR activated by Spd promotes translation of key metabolic enzyme upstream open reading frame (uORF)-containing mRNAs, PAO and CuAO, by facilitating translation reinitiation and providing feedback to polyamine metabolism and TOR activation. The Spd-TOR relay protected young-age seedlings of maize from expeditious stress heat shock. Our results demonstrate Spd is an upstream effector of TOR kinase in planta and provide its potential application for crop protection.

Keywords:  cell biology; plant biology; plant physiology

DOI:  https://doi.org/10.1016/j.isci.2021.103260
Molecules. 2021 Oct 30. pii: 6579. [Epub ahead of print]26(21):

Recent Advances in the Synthesis of Polyamine Derivatives and Their Applications.

Artemiy Nichugovskiy, Gian Cesare Tron, Mikhail Maslov.

  Biogenic polyamines (PAs) are involved in the growth and development of normal cells, and their intracellular concentration is stable. The concentration of PAs in cancer cells is significantly increased to promote and sustain their rapid proliferation. Over the years, synthetic PAs, which differ in their structure, have demonstrated high antitumor activity and are involved in clinical trials. The chemical synthesis of PAs and their conjugates require the correct choice of synthetic pathways-methods for constructing conjugates and the orthogonal protection of amino groups. The most common methods of synthesis of PA conjugates are acylation of regioselectively protected PAs or their alkylation under the conditions of the Fukuyama reaction. One of the most promising methods of PA synthesis is the use of a multicomponent Ugi reaction, which allows various PAs to be obtained in high yields. In this review, we describe and analyze various approaches that are used in the synthesis of polyamines and their conjugates.

Keywords:  Ugi reaction; antimalarial agents; antitumor activity; polyamine conjugates; polyamines

DOI:  https://doi.org/10.3390/molecules26216579
Microbiome. 2021 Nov 11. 9(1): 224

Polyamine metabolism links gut microbiota and testicular dysfunction.

Qi Zhao, Jian-Feng Huang, Yan Cheng, Man-Yun Dai, Wei-Feng Zhu, Xiu-Wei Yang, Frank J Gonzalez, Fei Li.

   BACKGROUND: Male fertility impaired by exogenous toxins is a serious worldwide issue threatening the health of the new-born and causing infertility. However, the metabolic connection between toxic exposures and testicular dysfunction remains unclear.
RESULTS: In the present study, the metabolic disorder of testicular dysfunction was investigated using triptolide-induced testicular injury in mice. We found that triptolide induced spermine deficiency resulting from disruption of polyamine biosynthesis and uptake in testis, and perturbation of the gut microbiota. Supplementation with exogenous spermine reversed triptolide-induced testicular dysfunction through increasing the expression of genes related to early and late spermatogenic events, as well as increasing the reduced number of offspring. Loss of gut microbiota by antibiotic treatment resulted in depletion of spermine levels in the intestine and potentiation of testicular injury. Testicular dysfunction in triptolide-treated mice was reversed by gut microbial transplantation from untreated mice and supplementation with polyamine-producing Parabacteroides distasonis. The protective effect of spermine during testicular injury was largely dependent on upregulation of heat shock protein 70s (HSP70s) both in vivo and in vitro.
CONCLUSIONS: The present study linked alterations in the gut microbiota to testicular dysfunction through disruption of polyamine metabolism. The diversity and dynamics of the gut microbiota may be considered as a therapeutic option to prevent male infertility. Video Abstract.

Keywords:  Gut microbiota; Metabolomics; Polyamine metabolism; Testicular dysfunction

DOI:  https://doi.org/10.1186/s40168-021-01157-z
Saudi Pharm J. 2021 Oct;29(10): 1223-1232

Total ginsenosides promote the IEC-6 cell proliferation via affecting the regulatory mechanism mediated by polyamines.

Yiping Zhu, Anrong Wang, Ruliu Li, Huibin Zhu, Ling Hu, Weiwen Chen.

  Epithelial cell proliferation has been demonstrated to be a critical modality for mucosal repair after gastrointestinal mucosal injury. This research aimed to investigate the effect of total ginsenosides upon the proliferation of intestinal epithelial cells (IEC-6), and elucidate its potential mechanisms through polyamine-regulated pathway including the expression of proliferation-related proteins. Total ginsenosides (PGE3) were extracted from Panax ginseng, a Chinese herbal medicine, whose chromatogram was obtained by high performance liquid chromatographic method with evaporative light scattering detection (HPLC-ELSD). The cell proliferation, cell cycle distribution and the level of c-Myc, RhoA, Cdk2 proteins were detected to determine the effects of PGE3 at 25, 50 and100 mg/l doses on IEC-6. Furthermore, rats model of intestinal mucosal injury were induced by the subcutaneous injection of indomethacin, and the effect of Panax ginseng aqueous extracts (PGE1) on intestinal mucosal injury was observed. PGE3 could promote IEC-6 cell proliferation, reduce the proportion of G0/G1 phase cells and elevate the proportion of G2/M + S phase cells, and revert the proliferation and cell cycle arrest induced by DFMO (DL-a-difluoromethylornithine, an inhibitor of polyamines synthesis). PGE3 exposure enhanced the level of c-Myc, RhoA and Cdk2 proteins, and reversed the inhibition of these proteins expression induced by DFMO. The results of gross and pathological scores showed administration of PGE1 significantly alleviated intestinal mucosal injury of rats. Our findings indicate that total ginsenosides promoted the IEC-6 proliferation presumably via its regulation on cell cycle and the expression of proliferation-related proteins regulated by polyamines, and provided a novel perspective for exploring the repair effect of Panax ginseng upon gastrointestinal mucosal injury.

Keywords:  Cdk2, cyclin-dependent protein kinase 2; Cell cycle; Cell proliferation; DFMO, DL-α-difluoromethylornithine; IEC-6, intestinal epithelial cells; Intestinal epithelial cells; PGE, Panax ginseng extracts; PGE1, Panax ginseng aqueous extracts; PGE3, total ginsenosides; Protein expression; RQSS, reinforcing Qi strengthening spleen; RhoA, Ras homolog family member A; Total ginsenosides

DOI:  https://doi.org/10.1016/j.jsps.2021.09.007
Sci Rep. 2021 Nov 09. 11(1): 21997

Improving water deficit tolerance of Salvia officinalis L. using putrescine.

Maryam Mohammadi-Cheraghabadi, Seyed Ali Mohammad Modarres-Sanavy, Fatemeh Sefidkon, Sajad Rashidi-Monfared, Ali Mokhtassi-Bidgoli.

To study the effects of foliar application of putrescine (distilled water (0), 0.75, 1.5, and 2.25 mM) and water deficit stress (20%, 40%, 60%, and 80% available soil water depletion (ASWD)) on the physiological, biochemical, and molecular attributes of Salvia officinalis L., a factorial experiment was performed in a completely randomized design with three replications in the growth chamber. The results of Real-Time quantitative polymerase chain reaction (qRT-PCR) analysis showed that putrescine concentration, irrigation regime, and the two-way interaction between irrigation regime and putrescine concentration significantly influenced cineole synthase (CS), sabinene synthase (SS), and bornyl diphosphate synthase (BPPS) relative expression. The highest concentration of 1,8-cineole, camphor, α-thujone, β-thujone, CS, SS, and BPPS were obtained in the irrigation regime of 80% ASWD with the application of 0.75 mM putrescine. There was high correlation between expression levels of the main monoterpenes synthase and the concentration of main monoterpenes. The observed correlation between the two enzyme activities of ascorbate peroxidase (APX) and catalase (CAT) strongly suggests they have coordinated action. On the other hand, the highest peroxidase (PO) and superoxide dismutase (SOD) concentrations were obtained with the application of 0.75 mM putrescine under the irrigation regime of 40% ASWD. Putrescine showed a significant increase in LAI and RWC under water deficit stress. There was an increasing trend in endogenous putrescine when putrescine concentration was increased in all irrigation regimes. Overall, the results suggest that putrescine may act directly as a stress-protecting compound and reduced H2O2 to moderate the capacity of the antioxidative system, maintain the membrane stability, and increase secondary metabolites under water deficit stress.

DOI: https://doi.org/10.1038/s41598-021-00656-1
Front Physiol. 2021 ;12 735543

Red Blood Cell Metabolism in Pyruvate Kinase Deficient Patients.

Micaela K Roy, Francesca Cendali, Gabrielle Ooyama, Fabia Gamboni, Holmes Morton, Angelo D'Alessandro.

  Background: Pyruvate kinase deficiency (PKD) is the most frequent congenital enzymatic defect of glycolysis, and one of the most common causes of hereditary non spherocytic hemolytic anemia. Therapeutic interventions are limited, in part because of the incomplete understanding of the molecular mechanisms that compensate for the metabolic defect. Methods: Mass spectrometry-based metabolomics analyses were performed on red blood cells (RBCs) from healthy controls (n=10) and PKD patients (n=5). Results: In PKD patients, decreases in late glycolysis were accompanied by accumulation of pentose phosphate pathway (PPP) metabolites, as a function of oxidant stress to purines (increased breakdown and deamination). Markers of oxidant stress included increased levels of sulfur-containing compounds (methionine and taurine), polyamines (spermidine and spermine). Markers of hypoxia such as succinate, sphingosine 1-phosphate (S1P), and hypoxanthine were all elevated in PKD subjects. Membrane lipid oxidation and remodeling was observed in RBCs from PKD patients, as determined by increases in the levels of free (poly-/highly-unsaturated) fatty acids and acyl-carnitines. Conclusion: In conclusion, in the present study, we provide the first overview of RBC metabolism in patients with PKD. Though limited in scope, the study addresses the need for basic science to investigate pathologies targeting underrepresented minorities (Amish population in this study), with the ultimate goal to target treatments to health disparities.

Keywords:  metabolomics; oxidative stress; pyruvate kinase deficiency; red blood cells (erythrocytes); rural America; underrepresented minorities

DOI:  https://doi.org/10.3389/fphys.2021.735543
Nanoscale Adv. 2021 Oct 27. 3(21): 6007-6026

Emergence of cationic polyamine dendrimersomes: design, stimuli sensitivity and potential biomedical applications.

Partha Laskar, Christine Dufès.

For decades, self-assembled lipid vesicles have been widely used in clinics as nanoscale delivery systems for various biomedical applications, including treatment of various diseases. Due to their core-shell architecture and versatile nature, they have been successfully used as carriers for the delivery of a wide range of therapeutic cargos, including drugs and nucleic acids, in cancer treatment. Recently, surface-modified polyamine dendrimer-based vesicles, or dendrimersomes, have emerged as promising alternatives to lipid vesicles for various biomedical applications, due to their ease of synthesis, non-immunogenicity, stability in circulation and lower size polydispersity. This mini-review provides an overview of the recent advances resulting from the use of biomimetic hydrophobically-modified polyamine-based dendrimersomes towards biomedical applications, focusing mainly on the two most widely used polyamine dendrimers, namely polyamidoamine (PAMAM) and poly(propylene imine) (PPI) dendrimers.

DOI: https://doi.org/10.1039/d1na00536g
Anim Biotechnol. 2021 Nov 11. 1-14

Calcium-sensing receptor protects intestinal integrity and alleviates the inflammatory response via the Rac1/PLCγ1 signaling pathway.

Guangmang Liu, Jie Zheng, Ke Gu, Caimei Wu, Gang Jia, Hua Zhao, Xiaoling Chen, Jing Wang.

  This study aimed to test the hypothesis that the calcium-sensing receptor (CaSR) can protect intestinal epithelial barrier integrity and decrease inflammatory response mediated by the Ras-related C3 botulinum toxin substrate 1 (Rac1)/phospholipase Cγ1 (PLC-γ1) signaling pathway. IPEC-J2 monolayers were treated without or with TNF-α in the absence or presence of CaSR antagonist (NPS 2143), CaSR overexpression, and Rac1 silencing, PLCγ1 silencing or spermine. Results showed that spermine increased transepithelial electrical resistance (TER), tight junction protein levels, the protein concentration of Rac1/PLC-γ1 signaling pathway, and decreased paracellular permeability in the presence of TNF-α. NPS2143 inhibited spermine-induced change in above-mentioned parameters. CaSR overexpression increased TER, the levels of tight junction proteins and the protein concentration of CaSR, phosphorylated PLCγ1, Rac1, and IP3, and decreased paracellular permeability and contents of interleukin-8 (IL-8) and TNF-α after TNF-α challenge. Rac1 and PLCγ1 silencing inhibited CaSR-induced increase in barrier function and the protein concentration of phosphorylated PLCγ1, Rac1, and IP3, and decrease in contents of IL-8 and TNF-α after TNF-α challenge. These results suggest that CaSR activation protects intestinal integrity and alleviates the inflammatory response by activating Rac1 and PLCγ1 signaling after TNF-α challenge, and spermine can maintain barrier function via CaSR/Rac1/PLC-γ1 pathway.

Keywords:  Calcium-sensing receptor; PLCγ1; Rac1; barrier function; repair of intestinal damage

DOI:  https://doi.org/10.1080/10495398.2021.1998090
Osteoporos Int. 2021 Nov 06.

Snyder-Robinson syndrome: differential diagnosis of osteogenesis imperfecta.

C Valera Ribera, À Martinez-Ferrer, E Flores Fernández, I Vázquez Gómez, A Orenes Vera, E Valls Pascual, D Ybáñez García, J J Alegre Sancho.

  Snyder-Robinson syndrome is an extremely rare genetic disorder, caused by mutations of the spermine synthase gene. We report a novel case of Snyder-Robinson syndrome, caused by a de novo mutation and first misdiagnosed with osteogenesis imperfecta. Clinical features, course, and genetic analysis are presented. The patient was treated with bisphosphonates for a decade, until developing an atypical femoral fracture. Teriparatide was then administered for 2 years and then changed to denosumab every 6 months, improving his bone density mass and preventing further fractures.

Keywords:  De novo mutation; Osteogenesis imperfecta; Osteoporosis; Snyder-Robinson syndrome; Spermine synthase; Spermine synthase gene

DOI:  https://doi.org/10.1007/s00198-021-06228-3
Nutrition. 2021 Oct 09. pii: S0899-9007(21)00375-0. [Epub ahead of print]93 111513

First reported case of pregnancy in a patient with ornithine aminotransferase deficiency.

Tomi Kanninen, Elizabeth Bryant, Celide Koerner, Bernard Gonik.

  Ornithine aminotransferase deficiency is a rare autosomalrecessive human inborn error of the metabolism resulting in hyperornithinemia and progressive chorioretinal degeneration (gyrate atrophy) with blindness. There are few reports in the literature and none that address this condition during pregnancy. We report on a novel case of ornithine aminotransferase deficiency during pregnancy that was managed actively with arginine and protein restriction with serial amino acid and fetal growth monitoring, resulting in an uncomplicated term live birth.

Keywords:  Gyrate atrophy of the choroid and retina; Ornithine aminotransferase deficiency; Pregnancy

DOI:  https://doi.org/10.1016/j.nut.2021.111513