bims-polyam 2023-12-17 papers

Issue of 2023–12–17
seven papers selected by
Sebastian J. Hofer, University of Graz

Cell Rep. 2023 Dec 12. pii: S2211-1247(23)01583-8. [Epub ahead of print]42(12): 113571

A spermidine riboswitch class in bacteria exploits a close variant of an aptamer for the enzyme cofactor S-adenosylmethionine.

Hubert Salvail, Aparaajita Balaji, Adam Roth, Ronald R Breaker.

Natural polyamines such as spermidine and spermine cations have characteristics that make them highly likely to be sensed by riboswitches, such as their general affinity to polyanionic RNA and their broad contributions to cell physiology. Despite previous claims that polyamine riboswitches exist, evidence of their biological functions has remained unconvincing. Here, we report that rare variants of bacterial S-adenosylmethionine-I (SAM-I) riboswitches reject SAM and have adapted to selectively sense spermidine. These spermidine-sensing riboswitch variants are associated with genes whose protein products are directly involved in the production of spermidine and other polyamines. Biochemical and genetic assays demonstrate that representatives of this riboswitch class robustly function as genetic "off" switches, wherein spermidine binding causes premature transcription termination to suppress the expression of polyamine biosynthetic genes. These findings confirm the existence of natural spermidine-sensing riboswitches in bacteria and expand the list of variant riboswitch classes that have adapted to bind different ligands.

Keywords: CP: Molecular biology; SAM; aptamer; gene control; polyamine; spermidine; transcription termination

DOI: https://doi.org/10.1016/j.celrep.2023.113571

Kidney Dis (Basel). 2023 Dec;9(6): 469-484

Metabolism of Polyamines and Kidney Disease: A Promising Therapeutic Target.

Dan Luo, Xiaohui Lu, Yi Li, Yiping Xu, Yi Zhou, Haiping Mao.

Background: More than 850 million people worldwide suffer from acute and chronic kidney diseases (CKD) which are tremendous socioeconomic burdens for society. Currently, the treatment choices for CKD are limited. There is a great need to understand the underlying mechanisms of the development of CKD in order to develop potential therapeutic strategies.
Summary: The alteration in cellular metabolism has emerged as an important common pathological mechanism in different kidney diseases. Metabolic intervening and reprogramming will yield new insights to prevent and slow the progression of kidney disease. As one essential component of cellular metabolisms in fuel-source preferences (glucose, fatty acids, or ketones), the polyamine compound metabolism comprising the metabolites (spermine, spermidine, and putrescine) and their biosynthetic and catabolic enzymes are an endogenous pathophysiological regulator that is arising as a potential therapeutic object for many diseases.
Key Messages: This article aimed to review current knowledge on polyamine metabolism and physiological processes, and its potential regulatory and beneficial roles in immunoregulation, mitochondrial homeostasis, autophagy, DNA damage, and kidney diseases, and thus provide a novel therapeutic opportunity for kidney diseases.

Keywords: Kidney disease; Polyamines; Spermidine; Spermine; Therapeutic potential

DOI: https://doi.org/10.1159/000533296

Plants (Basel). 2023 Nov 30. pii: 4031. [Epub ahead of print]12(23):

Evaluation of Salt Stress-Induced Changes in Polyamine, Amino Acid, and Phytoalexin Profiles in Mature Fruits of Grapevine Cultivars Grown in Tunisian Oases.

Abir Habib, Sihem Ben Maachia, Ahmed Namsi, Mounira Harbi Ben Slimane, Philippe Jeandet, Aziz Aziz.

Salinity stress has become an increasing threat to viticulture in the Tunisian oasis, and more generally, the characterization of salinity tolerance markers can be of great interest for sustainable grape production. This study investigated some metabolic adaptations in different tissues of the ripe berries of indigenous grapevine cultivars after exposure to salt stress to identify the key traits of salt stress tolerance under oasis conditions. We especially focused on the adaptive responses occurring at the level of amino acids, polyamines, and stilbene phytoalexins in the grape berry skin, pulp, and seeds of six grapevine cultivars differing in phenotypic and ampelographic characteristics. Our data showed that amino acids accumulated strongly in the pulp and skin, while resveratrol, trans-piceid and trans-ε-viniferin, as major phytoalexins, significantly accumulated in the seeds. High salinity was also found to increase both the berry skin and pulp contents of essential amino acids such as threonine, valine, leucine, isoleucine, lysine, methionine, and phenylalanine. The amounts of stilbenes also increased under high salinity in the berry skin of all the studied cultivars. Polyamine homeostasis within the different berry tissues suggested enhanced polyamine biosynthesis rather than polyamine oxidation in response to high salinity. Our principal component analysis revealed a clear discrimination between the cultivars based on their metabolic profiles within the ripe berry tissues under high salinity.

Keywords: amino acids; berry; grapevine; high salinity; oasis table cultivars; phytoalexins; polyamines; salt stress

DOI: https://doi.org/10.3390/plants12234031

Int J Mol Sci. 2023 Nov 25. pii: 16738. [Epub ahead of print]24(23):

Dynamic Interplay of Metabolic and Transcriptional Responses in Shrimp during Early and Late Infection Stages of Enterocytozoon hepatopenaei (EHP).

Leiting Zhang, Sheng Zhang, Yi Qiao, Xiaohui Cao, Jie Cheng, Qingguo Meng, Hui Shen.

Enterocytozoon hepatopenaei (EHP) is a microsporidian parasite that infects Litopenaeus vannamei, causing severe hepatopancreatic microsporidiosis (HPM) and resulting in significant economic losses. This study utilizes a combined analysis of transcriptomics and metabolomics to unveil the dynamic molecular interactions between EHP and its host, the Pacific white shrimp, during the early and late stages of infection. The results indicate distinct immunological, detoxification, and antioxidant responses in the early and late infection phases. During early EHP infection in shrimp, immune activation coincides with suppression of genes like Ftz-F1 and SEPs, potentially aiding parasitic evasion. In contrast, late infection shows a refined immune response with phagocytosis-enhancing down-regulation of Ftz-F1 and a resurgence in SEP expression. This phase is characterized by an up-regulated detoxification and antioxidant response, likely a defense against the accumulated effects of EHP, facilitating a stable host-pathogen relationship. In the later stages of infection, most immune responses return to baseline levels, while some immune genes remain active. The glutathione antioxidant system is suppressed early on but becomes activated in the later stages. This phenomenon could facilitate the early invasion of EHP while assisting the host in mitigating oxidative damage caused by late-stage infection. Notably, there are distinctive events in polyamine metabolism. Sustained up-regulation of spermidine synthase and concurrent reduction in spermine levels suggest a potential role of polyamines in EHP development. Throughout the infection process, significant differences in genes such as ATP synthase and hexokinase highlight the continuous influence on energy metabolism pathways. Additionally, growth-related pathways involving amino acids such as tryptophan, histidine, and taurine are disrupted early on, potentially contributing to the growth inhibition observed during the initial stages of infection. In summary, these findings elucidate the dynamic interplay between the host, Litopenaeus vannamei, and the parasite, EHP, during infection. Specific phase differences in immune responses, energy metabolism, and antioxidant processes underscore the intricate relationship between the host and the parasite. The disruption of polyamine metabolism offers a novel perspective in understanding the proliferation mechanisms of EHP. These discoveries significantly advance our comprehension of the pathogenic mechanisms of EHP and its interactions with the host.

Keywords: Enterocytozoon hepatopenaei; Litopenaeus vannamei; host-parasite interaction; metabolomics; transcriptome

DOI: https://doi.org/10.3390/ijms242316738

Biochim Biophys Acta Mol Cell Res. 2023 Dec 11. pii: S0167-4889(23)00220-3. [Epub ahead of print] 119647

The dynamics of the electrotactic reaction of mouse 3T3 fibroblasts.

Slawomir Lasota, Eliza Zimolag, Sylwia Bobis-Wozowicz, Jagoda Pilipiuk, Zbigniew Madeja.

The molecular mechanisms behind electrotaxis remain largely unknown, with no identified primary direct current electric field (dcEF) sensor. Two leading hypotheses propose mechanisms involving the redistribution of charged components in the cell membrane (driven by electrotaxis of electroosmosis) and the asymmetric activation of ion channels. To investigate these mechanisms, we studied the dynamics of electrotactic behaviour of mouse 3T3 fibroblasts. We observed that 3T3 fibroblasts exhibit cathodal migration within just 1 min when exposed to physiological dcEF. This rapid response suggests the involvement of ion channels in the cell membrane. Our large-scale screening method identified several ion channel genes as potential key players, including the inwardly rectifying potassium channel Kir4.2. Blocking the Kir channel family with Ba2+ or silencing the Kcnj15 gene, encoding Kir4.2, significantly reduced the directional migration of 3T3 cells. Additionally, the levels of the intracellular regulators of Kir channels, spermine (SPM) and spermidine (SPD), had a significant impact on cell directionality. Interestingly, inhibiting Kir4.2 resulted in the temporary cessation of electrotaxis for approximately 1-2 h before its return. This observation suggests a two-phase mechanism for the electrotaxis of mouse 3T3 fibroblasts, where ion channel activation triggers the initial rapid response to dcEF, and the subsequent redistribution of membrane receptors sustains long-term directional movement. In summary, our study unveils the involvement of Kir channels and proposes a biphasic mechanism to explain the electrotactic behaviour of mouse 3T3 fibroblasts, shedding light on the molecular underpinnings of electrotaxis.

Keywords: Directional movement; Dynamics; Electric field; Electrotaxis; Fibroblasts; Ion channels

DOI: https://doi.org/10.1016/j.bbamcr.2023.119647

Microbiol Spectr. 2023 Dec 14. e0356823

Spermine enhances the activity of anti-tuberculosis drugs.

Carine Sao Emani, Norbert Reiling.

IMPORTANCE: This is the first study that attempted to demonstrate the mechanisms of reactive oxygen species (ROS) generation by spermine (Spm) in Mycobacterium tuberculosis (M.tb). Furthermore, this is the first study to demonstrate that it is able to enhance the activity of currently available and World Health Organization (WHO)-approved tuberculosis (TB) drugs. Spermine can easily be obtained since it is already found in our diet. Moreover, as opposed to conventional antibiotics, it is less toxic to humans since it is found in millimolar concentrations in the body. Finally, with the difficulty of curing TB with conventional antibiotics, this study suggests that less toxic molecules, such as Spm, could in a long-term perspective be incorporated in a TB regimen to boost the treatment.

Keywords: Mycobacterium tuberculosis (M.tb); bedaquiline (BDQ); cumene hydroperoxide (CuOOH); isoniazid (INH); para-aminosalicylic acid (PAS); reactive oxygen species (ROS); rifampicin (RIF); spermine (Spm); tuberculosis (TB)

DOI: https://doi.org/10.1128/spectrum.03568-23

Hematology. 2023 Dec;28(1): 2265187

Adult presentation of ornithine transcarbamylase deficiency: a possible cause of hyperammonemia after high-dose chemotherapy and stem cell transplantation.

Galina Tsykunova, Erle Kristensen, Asbjørg Stray-Pedersen, Øyvind Bruserud, Ida Wiig Sørensen, Øystein Bruserud, Tor Henrik Anderson Tvedt.

Hyperammonemia is a rare and often fatal complication following the conditioning therapy in autologous and allogeneic stem cell transplant recipients. It is characterized by anorexia, vomiting, lethargy and coma without any other apparent cause. The diagnosis is often delayed because symptoms can be subtle and ammonia is usually not included among the routine analyzes. Previous reports have not identified the molecular mechanisms behind hyperammonemia in stem cell transplant recipients. Urea cycle disorders (UCDs) are inborn errors of metabolism leading to hyperammonemia that usually presents in early childhood, whereas first presentation in adults is less common. Here we describe an adult woman with hyperammonemia following autologous stem cell transplantation for multiple myeloma. No apparent cause of hyperammonemia was identified, including portosystemic shunting, liver dysfunction or recent hyperammonemia-inducing chemotherapy. Hyperammonemia, normal blood glucose as well as anion gap and a previous history of two male newborns that died early after birth, prompted biochemical and genetic investigations for a UCD. A heterozygous variant in the X-linked gene encoding ornithine transcarbamylase (OTC) was identified and was regarded as a cause of UCD. The patient improved after treatment with nitrogen scavengers and high caloric intake according to a UCD protocol. This case report suggests that UCD should be considered as a possible cause of hyperammonemia following stem cell transplantation.

Keywords: Bone marrow transplantation; hyperammonemia; urea cycle disorder

DOI: https://doi.org/10.1080/16078454.2023.2265187