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ZDHHC9 and spermine metabolism: a palmitoylation-driven pathway to prostate carcinogenesis.

BACKGROUND: Spermine is a natural metabolite that has been shown to hinder the progression of prostate cancer. Protein palmitoylation, a recently identified post-translational lipid modification, is catalyzed by a family of 23 enzymes known as zinc finger DHHC-type palmitoyltransferases (ZDHHCs). This study primarily investigates the role of ZDHHC9 in spermine metabolism and its potential association with prostate cancer. METHODS: We employed immunohistochemistry, Western blotting, and RT-qPCR techniques to assess ZDHHC9 expression in prostate cancer tissues and cell lines. The connection betw…

Cation permeability induced by spermine and Polybrene in rat liver mitochondria.

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Spermidine/spermine N1-acetyltransferase1mediates zearalenone-induced toxicity in bovine Leydig cells.

INTRODUCTION: Zearalenone (Zea), a widespread mycotoxin, can impair male reproductive function, but its effects on bovine Leydig cells and the underlying mechanisms remain insufficiently understood. METHODS: Primary bovine Leydig cells were isolated and identified. The effects of Zea on cell viability, testosterone production, steroidogenic gene expression, oxidative stress, apoptosis, and cell cycle progression were examined. Transcriptomic analysis was performed to identify genes associated with Zea-induced cellular injury, and the role of spermidine/spermine N1-acetyltransferase1 (SAT1) wa…

Spermine Lipid Assembled Nanoparticles for siRNA Delivery and Androgenetic Alopecia Therapy.

Androgenetic alopecia (AGA) is characterized by progressive hair loss caused by abnormal androgen levels in hair follicles, which has a subs … delivery, potential inflammatory responses, and poor in vivo retention capacity. Here, a series of spermine-derived ionizable lipids with varying alkyl chains (Sper-N, N = 8, 12, 16) were synthesized and subsequently coformulated with DSPC and a PEG-lipid to generate Sper-N/siRNA lipid nanoparticles. In vitro studies have demonstrated that Sper-12-based n …

Spermine oxidase regulates liver inflammation and fibrosis through β-catenin pathway.

BACKGROUND: Spermine oxidase (SMOX), an inducible enzyme involved in the catabolic pathway of polyamine, was found to be upregulated in hepatocellular carcinoma and might be an important oncogene of it in our previous studies. This study attempted to further investigate its relationship with liver inflammation and fibrosis both in vitro and in vivo. METHODS: The effect of SMOX inhibition on LPS-induced inflammatory response in mouse liver cell line AML12 was validated by using small interfering RNA or SMOX inhibitor MDL72527. Western blotting and immunofluorescence were utilized to verify whe…

Spermine: Its Emerging Role in Regulating Drought Stress Responses in Plants.

In recent years, research on spermine (Spm) has turned up a lot of new information about this essential polyamine, especially as it is able to counteract damage from abiotic stresses. Spm has been shown to protect plants from a variety of environmental insults, but whether it can prevent the adverse effects of drought has not yet been reported. Drought stress increases endogenous Spm in plants and exogenous application of Spm improves the plants' ability to tolerate drought stress. Spm's role in enhancing antioxidant defense mechanisms, glyoxalase systems, methylglyoxal (MG) detoxification, an…

Safety profile of dextran-spermine gene delivery vector in mouse lungs.

A nano-sized polymer, dextran-spermine (D-SPM), was shown to have the capacity to deliver gene to the lung of mouse via intranasal route. In this study, assessments on the safety profile of D-SPM were performed to complement the gene expression results. African green monkey kidney fibroblast (COS-7) and human adenocarcinoma breast (MCF-7) cells transfected with D-SPM/pDNA showed massive reduction in the number of viable cells. As for in vivo study, elevated level of neutrophils was observed, despite the minimal level of pro-inflammatory cytokines (TNF-alpha, IL-12, IFN-gamma) detected in the b…

Spermidine/spermine N1-acetyltransferase-1 as a diagnostic biomarker in human cancer.

AimSSAT-1 is an enzyme that plays a critical role in cell growth. Amantadine, a FDA-approved antiviral drug, is a substrate for SSAT-1. The utility of amantadine as an agent to demonstrate elevated SSAT-1 activity linked to cancer was conducted.ResultsHigh levels of SSAT-1 expression were measured in tumor human cell lines, and in breast, prostate and lung tumor tissue. An increase in the urinary levels of acetylated amantadine in cancer patients was observed.ConclusionIncreases in SSAT-1 contents in tumor tissue could be of value in targeting cancers with high SSAT-1 expression for confirmati

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… Chem. 291 29 14904 14912 2016 27268251 10.1074/jbc.R116.731661 PMC4946908 4 Pegg AE Spermidine/spermine- N(1) -acetyltransferase: a key metabolic regulator Am. J. Physiol. Endocrinol. … Metab. 294 6 E995 E1010 2008 18349109 10.1152/ajpendo.90217.2008 •• An excellent and comprehensive review of the cellular function of spermidine/spermine N1-acetyl transferase (SSAT). 5 Babbar N Hacker A Huang Y Casero RA Tumor necrosis factor α induces spermidine/spermine N1-acetyltransferase through …

Spermine improves recognition memory deficit in a rodent model of Huntington's disease.

Huntington's disease (HD) is a progressive neurodegenerative disorder associated with motor and cognitive impairment. Intrastriatal administration of quinolinic acid (QA) causes neurodegeneration, glial proliferation and cognitive impairment in animals, which are similar to these seen in human HD. Since polyamines improve memory in cognitive tasks, we now tested if the post-training intrastriatal administration of spermine, an agonist of the polyamine site at the NMDA receptor, reverses the deficits in the object recognition task induced by QA. Bilateral striatal injections of QA (180 or 360 n…

Reduction of postoperative adhesions by N,O-carboxymethylchitosan and spermine NONOate in rats.

BACKGROUND: Postsurgical adhesions can occur following virtually all types of surgery, resulting in serious clinical complications. Therefore, prevention of adhesions is an important goal of surgical practice. A rat uterine horn model was used to investigate the efficacy of N,O-carboxymethylchitosan (NOCC) and spermine NONOate (SPER/NO) alone and in combination in preventing adhesion formation. METHODS: Sixty Wistar albino rats underwent bilateral uterine horn injury with a unipolar cautery. Study groups were as follows: (i) control group, no adjuvant therapy; and those with adjuvant applied,…

[Exogenous spermine alleviates myocardial injury induced by hyperglycemia by inhibiting golgi stress].

OBJECTIVE: To investigate whether Golgi stress (GAS) is involved in diabetic cardiomyopathy (DCM) and whether myocardial protection of exogenous spermine is associated with regulation of GAS. METHODS: Sixty Wistar rats were randomly divided into normal control group (Control), diabetic group (T1D, STZ 60 mg/kg intraperitoneal injection) and spermine group (T1D+Sp, spermine 5 mg/(kg·d) intraperitoneal injection) for 12 weeks. H9C2 rat cardiomyocytes were randomly divided into control group (Control, 10% FBS-DMEM culture), high glucose group (HG, 10% FBS-DMEM+40 mmol/L glucose) and spermine gro…

Coating with spermine-pullulan polymer enhances adenoviral transduction of mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are adult stem cells with multilineage potential, which makes them attractive tools for regenerative medicine … us and adenovirus receptors expression. To overcome this problem, we developed an Adv coated with a spermine-pullulan (SP) cationic polymer and investigated its physicochemical properties and internalization mechanisms. We demonstrated that the SP coating could enhance adenoviral transduction of MSCs without detectable cytotoxicity or effects on differenti …

Diagnostic screening for spermine synthase deficiency by liquid chromatography tandem mass spectrometry.

BACKGROUND: Snyder-Robinson syndrome is an X-linked genetic disorder characterized by intellectual disability, facial asymmetry, thickened lower lip, long hands with hyper extendable fingers, slow speech, and hyposcoliosis. The disorder is caused by a mutation in the spermine synthase (SMS) gene. The SMS gene encodes an enzyme involved in polyamine metabolism. Specifically, individuals with Snyder-Robinson have lack or have diminished capability to covert spermidine to spermine. METHODS: We developed a liquid chromatography tandem mass spectrometry (LC-MS/MS) based screen for Snyder-Robinson …

Spermine and spermidine mediate protection against oxidative damage caused by hydrogen peroxide.

The polyamines spermidine and spermine have been hypothesized to possess different functions in the protection of DNA from reactive oxygen species. The growth and survival of mouse fibroblasts unable to synthesize spermine were compared to their normal counterparts in their native and polyamine-depleted states in response to oxidative stress. The results of these studies suggest that when present at normal or supraphysiological concentrations, either spermidine or spermine can protect cells from reactive oxygen species. However, when polyamine pools are pharmacologically manipulated to produce…

X-linked spermine synthase gene (SMS) defect: the first polyamine deficiency syndrome.

Polyamines (putrescine, spermidine, spermine) are ubiquitous, simple molecules that interact with a variety of other molecules in the cell, including nucleic acids, phospholipids and proteins. Various studies indicate that polyamines are essential for normal cell growth and differentiation. Furthermore, these molecules, especially spermine, have been shown to modulate ion channel activities of certain cells. Nonetheless, little is known about the specific cellular functions of these compounds, and extensive laboratory investigations have failed to identify a heritable condition in humans in wh…

[Influence of Mg ions and spermine on ATP-dependent Ca2+ transport in myometrial intracellular structures. II. Comparative study of spermine, Mg ions and cyclosporin A effects on Ca2+ transport in mitochondria].

In experiments carried out with the use of the radioactive label (45Ca2+) on suspension of the rat uterus myocytes processed by digitonin solution (0.1 mg/ml), influence of spermine and cyclosporin A on Mg2+, ATP-dependent Ca2+ transport in mitochondria at different Mg2+ concentration were investigated. Ca2+ accumulation in mitochondria was tested as such which was not sensitive to thapsigargin (100 nM) and was blocked by ruthenium red (10 microM). It has been shown, that spermine (1 mM) stimulates Mg2+, ATP-dependent Ca2+ accumulation in mitochondria irrespective of Mg2+ concentration (3 or 7…

Arginine downstream metabolites spermidine and putrescine, but not spermine, contribute to PCV2 replication.

Porcine circovirus type 2 (PCV2), a major pathogen of PCV2-associated diseases, causes immense economic losses. Understanding the cellular m … tment suppressed PCV2 replication. Supplementation with exogenous spermidine or putrescine, but not spermine, strikingly facilitated PCV2 replication, and inhibition of polyamine biogenesis significantly curtailed PCV2 replication in vitro and in the murine model. Taken together, the study revealed that spermidine plays an important proviral role in PCV2 r …

Palladium(II) anticancer agents: the intricate case of the Pd-spermine complex.

Palladium-based anticancer drugs are promising alternatives to platinum agents, with potential to overcome acquired resistance and reduce side effects. Among them, the dinuclear Pd(II)-spermine complex (Pd2Spm) has shown notable cytostatic activity in vitro. However, its synthesis mechanism and structural properties remain poorly understood, which hinders further development. This study reports an optimised synthetic route for Pd2Spm, revealing pH dependence and temperature-induced isomeric changes. These variations were thoroughly characterised by vibrational spectroscopy, leading to the iden…

Triclabendazole and clofazimine reduce replication and spermine uptake in vitro in Toxoplasma gondii.

Toxoplasmosis is a worldwide zoonosis caused by the protozoan parasite Toxoplasma gondii. Although this infection is generally asymptomatic … her selectivity against T. gondii, affecting its replication. Furthermore, both compounds inhibited spermine incorporation into the parasite, which is necessary for the formation of other polyamines. The data reported here indicate that clofazimine and triclabendazole could be used for the treatment of human toxoplasmosis and confirms that drug repurposing …

Spermine and Spermidine Alter Gene Expression and Antigenic Profile of Borrelia burgdorferi.

Borrelia burgdorferi, the agent of Lyme disease, responds to numerous host-derived signals to alter adaptive capabilities during its enzooti … conditions in B. burgdorferi Among several polyamines and polyamine precursors, supplementation of spermine or spermidine in the borrelial growth medium induced synthesis of major regulators of gene expression in B. burgdorferi, such as RpoS and BosR, with a concomitant increase in proteins that contribute to colonization and survival of B. burgdorferi in …