bims-polyam 2022-10-16 papers

Issue of 2022–10–16
six papers selected by
Sebastian J. Hofer, University of Graz

Int J Mol Sci. 2022 Oct 05. pii: 11818. [Epub ahead of print]23(19):

Spermine Suppresses Adipocyte Differentiation and Exerts Anti-Obesity Effects In Vitro and In Vivo.

Sachie Nakatani, Yasuhiro Horimoto, Natsumi Nakabayashi, Mayumi Karasawa, Masahiro Wada, Kenji Kobata.

Endogenous polyamines such as putrescine (Put), spermidine (Spd), and spermine (Spm) affect adipocyte differentiation. In this study, we investigated the effect of exogenously supplemented polyamines on mouse adipocyte differentiation and anti-obesity actions in vitro and in vivo. The preadipocyte cell line, 3T3-L1, was cultured with Put, Spd, or Spm, and lipid accumulation in the cells was measured by Oil Red O staining. Lipid accumulation was significantly suppressed by Spm. Suppression of CCAAT/enhancer binding protein α mRNA by Spm suggested that the decreased lipid accumulation was due to delaying the cell differentiation. The body weight and fat of obese mice induced with a high-fat diet were reduced by oral ingestion of Spm. In conclusion, oral supplementation of Spm has the ability to prevent obesity through inhibition of adipocyte differentiation.

Keywords: adipocyte; differentiation; obesity; polyamine; spermine

DOI: https://doi.org/10.3390/ijms231911818

Plant Physiol Biochem. 2022 Sep 30. pii: S0981-9428(22)00444-2. [Epub ahead of print]192 110-119

Ornithine decarboxylase regulates putrescine-related metabolism and pollen development in Atropa belladonna.

Tengfei Zhao, Junlan Zeng, Mei Yang, Fei Qiu, Yueli Tang, Lingjiang Zeng, Chunxian Yang, Ping He, Xiaozhong Lan, Min Chen, Zhihua Liao, Fangyuan Zhang.

Polyamines, including putrescine, spermidine, and spermine, play critical roles in cell physiology by different forms. As a rate-limiting enzyme that converts ornithine to putrescine, ornithine decarboxylase (ODC, EC 1.1.1.37) has been studied in detail in animals and microorganisms, but its specific functions are poorly understood in plants. In this study, the metabolic and developmental roles of the ODC gene were studied through RNAi-mediated suppression of the ODC gene (AbODC) in A. belladonna. Suppression of AbODC reduced the production of precursors of medicinal tropane alkaloids, including putrescine and N-methylputrescine, as well as hyoscyamine and scopolamine. In AbODC-RNAi roots, the production of putrescine and spermidine in free form was reduced, but in the AbODC-RNAi leaves, the content of free polyamines was not altered. In the roots/leaves of AbODC-RNAi plants, the production of conjugated and bound polyamines was reduced. In addition, suppression of the ODC gene resulted in reduction of polyamines and pollen sterility in AbODC-RNAi flowers. In floral organs, GUS-staining results indicated that AbODC was domainantly expressed in pollen. In summary, ornithine decarboxylase not only plays a key role in regulating the biosynthesis of diverse forms of polyamines and medicinal tropane alkaloids, but also participates in pollen development.

Keywords: Atropa belladonna; Metabolism; Ornithine decarboxylase; Pollen development; Polyamines; Tropane alkaloids

DOI: https://doi.org/10.1016/j.plaphy.2022.09.030

Int J Mol Sci. 2022 Sep 20. pii: 10986. [Epub ahead of print]23(19):

The Impact of Spermidine on C2C12 Myoblasts Proliferation, Redox Status and Polyamines Metabolism under H2O2 Exposure.

Roberta Ceci, Guglielmo Duranti, Stefano Giuliani, Marianna Nicoletta Rossi, Ivan Dimauro, Stefania Sabatini, Paolo Mariottini, Manuela Cervelli.

A central feature of the skeletal muscle is its ability to regenerate through the activation, by environmental signals, of satellite cells. Once activated, these cells proliferate as myoblasts, and defects in this process profoundly affect the subsequent process of regeneration. High levels of reactive oxygen species such as hydrogen peroxide (H2O2) with the consequent formation of oxidized macromolecules increase myoblasts' cell death and strongly contribute to the loss of myoblast function. Recently, particular interest has turned towards the beneficial effects on muscle of the naturally occurring polyamine spermidine (Spd). In this work, we tested the hypothesis that Spd, upon oxidative challenge, would restore the compromised myoblasts' viability and redox status. The effects of Spd in combination with aminoguanidine (Spd-AG), an inhibitor of bovine serum amine oxidase, on murine C2C12 myoblasts treated with a mild dose of H2O2 were evaluated by analyzing: (i) myoblast viability and recovery from wound scratch; (ii) redox status and (iii) polyamine (PAs) metabolism. The treatment of C2C12 myoblasts with Spd-AG increased cell number and accelerated scratch wound closure, while H2O2 exposure caused redox status imbalance and cell death. The combined treatment with Spd-AG showed an antioxidant effect on C2C12 myoblasts, partially restoring cellular total antioxidant capacity, reducing the oxidized glutathione (GSH/GSSG) ratio and increasing cell viability through a reduction in cell death. Moreover, Spd-AG administration counteracted the induction of polyamine catabolic genes and PA content decreased due to H2O2 challenges. In conclusion, our data suggest that Spd treatment has a protective role in skeletal muscle cells by restoring redox balance and promoting recovery from wound scratches, thus making myoblasts able to better cope with an oxidative insult.

Keywords: glutathione; myoblasts proliferation; polyamines homeostasis; redox homeostasis; spermidine

DOI: https://doi.org/10.3390/ijms231910986

Molecules. 2022 Sep 21. pii: 6218. [Epub ahead of print]27(19):

Synthesis of Novel Lipophilic Polyamines via Ugi Reaction and Evaluation of Their Anticancer Activity.

Artemiy Nichugovskiy, Varvara Maksimova, Ekaterina Trapeznikova, Elizaveta Eshtukova-Shcheglova, Igor Ivanov, Marianna Yakubovskaya, Kirill Kirsanov, Dmitry Cheshkov, Gian Cesare Tron, Mikhail Maslov.

Natural polyamines (PAs) are involved in the processes of proliferation and differentiation of cancer cells. Lipophilic synthetic polyamines (LPAs) induce the cell death of various cancer cell lines. In the current paper, we have demonstrated a new method for synthesis of LPAs via the multicomponent Ugi reaction and subsequent reduction of amide groups by PhSiH3. The anticancer activity of the obtained compounds was evaluated in the A-549, MCF7, and HCT116 cancer cell lines. For the first time, it was shown that the anticancer activity of LPAs with piperazine fragments is comparable with that of aliphatic LPAs. The presence of a diglyceride fragment in the structure of LPAs appears to be a key factor for the manifestation of high anticancer activity. The findings of the study strongly support further research in the field of LPAs and their derivatives.

Keywords: anticancer activity; lipophilic polyamines; multicomponent Ugi reaction; polyamines

DOI: https://doi.org/10.3390/molecules27196218

Am J Kidney Dis. 2022 Oct 09. pii: S0272-6386(22)00931-3. [Epub ahead of print]

Improving a Rare Metabolic Disorder Through Kidney Transplantation: A Case Report of a Patient With Lysinuric Protein Intolerance.

Ties IJzermans, Wilbert van der Meijden, Marlijn Hoeks, Marleen Huigen, Alexander Rennings, Tom Nijenhuis.

Lysinuric protein intolerance (LPI) is a rare metabolic disorder with reduced renal and intestinal reabsorption of ornithine, lysine and arginine, due to mutations in the SLC7A7 gene encoding the y+LAT1 transporter, leading to urea cycle defects with protein intolerance. Furthermore, chronic kidney disease (CKD) in LPI is common and can progress to end stage kidney disease requiring renal replacement therapy. Kidney transplantation could in theory improve urine levels and consequently plasma levels of these amino acids and therefore improve clinical symptoms as well as protein intolerance in LPI patients. However data on kidney transplantation in LPI patients is limited and up till now no data on clinical and biochemical improvement after kidney transplantation has been reported. In this case report we describe a rare case of kidney transplantation in a LPI patient with significant improvement in protein tolerance, plasma and urine levels of ornithine, lysine and arginine and on LPI symptoms.

Keywords: Lysinuric protein intolerance; amino acids, metabolic disorder; kidney transplantation; whole exome sequencing

DOI: https://doi.org/10.1053/j.ajkd.2022.08.019

Int J Dev Disabil. 2022 ;68(5): 609-614

High levels of blood glutamic acid and ornithine in children with intellectual disability.

Muhammad Wasim, Haq Nawaz Khan, Hina Ayesha, Abdul Tawab, Fazal E Habib, Muhammad Rafique Asi, Mazhar Iqbal, Fazli Rabbi Awan.

Objectives: Aminoacidopathies are inborn errors of metabolism (IEMs) that cause intellectual disability in children. Luckily, aminoacidopathies are potentially treatable, if diagnosed earlier in life. The focus of this study was the screening of aminoacidopathies in a cohort of patients suspected for IEMs. Methods: Blood samples from healthy (IQ > 90; n = 391) and intellectually disabled (IQ < 70; n = 409) children (suspected for IEMs) were collected from different areas of Northern Punjab, Pakistan. An analytical HPLC assay was used for the screening of plasma amino acids. Results: All the samples (n = 800) were analyzed on HPLC and forty-three out of 409 patient samples showed abnormal amino acid profiles mainly in the levels of glutamic acid, ornithine and methionine. Plasma concentration (Mean ± SD ng/mL) were significantly high in 40 patients for glutamic acid (patients: 165 ± 38 vs. controls: 57 ± 8, p < 0.00001) and ornithine (patients: 3177 ± 937 vs. controls: 1361 ± 91, p < 0.0001). Moreover, 3 patients showed abnormally high (53.3 ± 8.6 ng/mL) plasma levels of methionine. Conclusion: In conclusion, biochemical analysis of samples from such patients at the metabolites level could reveal the underlying diseases which could be confirmed through advanced biochemical and genetic analyses. Thus, treatment to some of such patients could be offered. Thus burden of intellectual disability caused by such rare metabolic diseases could be reduced from the target populations.

Keywords: Pakistan; aminoacidopathies; inborn errors of metabolism (IEMs); intellectual disability (ID); newborn screening (NBS)

DOI: https://doi.org/10.1080/20473869.2020.1858520