X-ray irradiated cultures of mouse cortical neural stem/progenitor cells recover cell viability and proliferation with dose-dependent kinetics.

Exposure of the developing or adult brain to ionizing radiation (IR) can cause cognitive impairment and/or brain cancer, by targeting neural stem/progenitor cells (NSPCs). IR effects on NSPCs include transient cell cycle arrest, permanent cell cycle exit/differentiation, or cell death, depending on the experimental conditions. In vivo studies suggest that brain age influences NSPC response to IR, but whether this is due to intrinsic NSPC changes or to niche environment modifications remains unclear.

Link between spermine oxidase and apoptosis antagonizing transcription factor: A new pathway in neuroblastoma.

Neuroblastoma (NB) is a heterogeneous extra‑cranial childhood type of cancer, responsible for approximately 15% of all paediatric cancer‑related deaths. Although several critical genetic aberrations have been related to NB, only a few established molecular markers have been associated with prognosis [V‑myc avian myelocytomatosis viral oncogene (MYCN) locus amplification, deletions of part of chromosome 1p, 11q23 and gain of 17q]. Regrettably, direct evidence of NB‑related tumour suppressors or oncogenes has not been currently identified at these chromosomal regions.

Leptin induction following irradiation is a conserved feature in mammalian epithelial cells and tissues.

Purpose: Leptin (LEP) is a peptide hormone with multiple physiological functions. Besides its systemic actions, it has important peripheral roles such as a mitogen action on keratinocytes following skin lesions. We previously showed that LEP mRNA is significantly induced in response to neutron irradiation in mouse skin and that the protein increases in the irradiated epidermis and in the related subcutaneous adipose tissue.

Adaptive responses of heart and skeletal muscle to spermine oxidase overexpression: Evaluation of a new transgenic mouse model.

Spermine oxidase oxidizes spermine to produce HO, spermidine, and 3-aminopropanal. It is involved in cell drug response, apoptosis, and in the etiology of several pathologies, including cancer. Spermine oxidase is an important positive regulator of muscle gene expression and fiber size and, when repressed, leads to muscle atrophy.

Polyamines metabolism and breast cancer: state of the art and perspectives.

Breast cancer (BC) is a common disease that generally occurs in women over the age of 50, and the risk is especially high for women over 60 years of age. One of the major BC therapeutic problems is that tumors initially responsive to chemotherapeutic approaches can progress to more aggressive forms poorly responsive to therapies. Polyamines (PAs) are small polycationic alkylamines, naturally occurring and essential for normal cell growth and development in eukaryotes.

Spermine metabolism and radiation-derived reactive oxygen species for future therapeutic implications in cancer: an additive or adaptive response.

Destruction of cells by irradiation-induced radical formation is one of the most frequent interventions in cancer therapy. An alternative to irradiation-induced radical formation is in principle drug-induced formation of radicals, and the formation of toxic metabolites by enzyme catalyzed reactions. Thus, combination therapy targeting polyamine metabolism could represent a promising strategy to fight hyper-proliferative disease.

Inflammation, carcinogenesis and neurodegeneration studies in transgenic animal models for polyamine research.

Natural polyamines (PA) are cationic molecules affecting cell growth and proliferation. An association between increased polyamine biosynthesis and inflammation-induced carcinogenesis has been recognised. On the other hand, there are indications that inflammatory stimuli can up-regulate polyamine catabolism and that altered polyamine metabolism could affect pro- and anti-inflammatory cytokines.

Reactive oxygen species spermine metabolites generated from amine oxidases and radiation represent a therapeutic gain in cancer treatments.

The most frequent interventions in cancer therapy are currently the destruction of cells by irradiation or administration of drugs both able to induce radical formation and toxic metabolites by enzyme-catalyzed reactions. The aim of this study was to determine the cell viability of cells undergoing a DNA damage threshold accomplished by ROS overproduction via both ectopic expression of murine spermine oxidase (mSMOX) and bovine serum amine oxidase (BSAO) enzymes. Low dose of X-irradiation delivers a challenging dose of damage as evaluated in proficient Chinese hamster AA8 cell line and both deficient transcription-coupled nucleotide excision repair (NER) UV61 cells and deficient base excision repair (BER) EM9 cells, at 6 and 24 h after exposure.

A New Transgenic Mouse Model for Studying the Neurotoxicity of Spermine Oxidase Dosage in the Response to Excitotoxic Injury.

Spermine oxidase is a FAD-containing enzyme involved in polyamines catabolism, selectively oxidizing spermine to produce H2O2, spermidine, and 3-aminopropanal. Spermine oxidase is highly expressed in the mouse brain and plays a key role in regulating the levels of spermine, which is involved in protein synthesis, cell division and cell growth. Spermine is normally released by neurons at synaptic sites where it exerts a neuromodulatory function, by specifically interacting with different types of ion channels, and with ionotropic glutamate receptors.

Structure-function relationships in the evolutionary framework of spermine oxidase.

Spermine oxidase is a FAD-dependent enzyme that specifically oxidizes spermine, and plays a central role in the highly regulated catabolism of polyamines in vertebrates. The spermine oxidase substrate is specifically spermine, a tetramine that plays mandatory roles in several cell functions, such as DNA synthesis, cellular proliferation, modulation of ion channels function, cellular signalling, nitric oxide synthesis and inhibition of immune responses. The oxidative products of spermine oxidase activity are spermidine, H2O2 and the aldehyde 3-aminopropanal that spontaneously turns into acrolein.

Molecular evolution of the polyamine oxidase gene family in Metazoa.

Background: Polyamine oxidase enzymes catalyze the oxidation of polyamines and acetylpolyamines. Since polyamines are basic regulators of cell growth and proliferation, their homeostasis is crucial for cell life. Members of the polyamine oxidase gene family have been identified in a wide variety of animals, including vertebrates, arthropodes, nematodes, placozoa, as well as in plants and fungi.

Spermine oxidase: ten years after.

Spermine oxidase (SMO) was discovered much more recently than other enzymes involved in polyamine metabolism; this review summarizes 10 years of researches on this enzyme. Spermine oxidase (SMO) is a FAD-dependent enzyme that specifically oxidizes spermine (Spm) and plays a dominant role in the highly regulated mammalian polyamines catabolism. SMO participates in drug response, apoptosis, response to stressful stimuli and etiology of several pathological conditions, including cancer.

Dose-dependent onset of regenerative program in neutron irradiated mouse skin.

Background: Tissue response to irradiation is not easily recapitulated by cell culture studies. The objective of this investigation was to characterize, the transcriptional response and the onset of regenerative processes in mouse skin irradiated with different doses of fast neutrons.

Methodology/principal Findings: To monitor general response to irradiation and individual animal to animal variation, we performed gene and protein expression analysis with both pooled and individual mouse samples.

Spermine oxidase (SMO) activity in breast tumor tissues and biochemical analysis of the anticancer spermine analogues BENSpm and CPENSpm.

Background: Polyamine metabolism has a critical role in cell death and proliferation representing a potential target for intervention in breast cancer (BC). This study investigates the expression of spermine oxidase (SMO) and its prognostic significance in BC. Biochemical analysis of Spm analogues BENSpm and CPENSpm, utilized in anticancer therapy, was also carried out to test their property in silico and in vitro on the recombinant SMO enzyme.

Increased spermine oxidase (SMO) activity as a novel differentiation marker of myogenic C2C12 cells.

Spermine oxidase (SMO) is a FAD-containing enzyme involved in animal cell polyamines (PA) homeostasis, selectively active on spermine and producing H(2)O(2), spermidine, and the 3-aminopropanal. In the present study, we have examined the SMO gene expression during the mouse myoblast C2C12 cell differentiation induced with two different stimuli by RT-PCR analysis, polysome-mRNP distribution and enzyme activity. SMO transcript accumulation and enzymatic activity increases during C2C12 cell differentiation and correlates with the decrease of spermine content.

Nonapoptotic role for Apaf-1 in the DNA damage checkpoint.

Apaf-1 is an essential factor for cytochrome c-driven caspase activation during mitochondrial apoptosis but has also an apoptosis-unrelated function. Knockdown of Apaf-1 in human cells, knockout of apaf-1 in mice, and loss-of-function mutations in the Caenorhabditis elegans apaf-1 homolog ced-4 reveal the implication of Apaf-1/CED-4 in DNA damage-induced cell-cycle arrest. Apaf-1 loss compromised the DNA damage checkpoints elicited by ionizing irradiation or chemotherapy.

Ret, Abl1 (cAbl) and Trp53 gene fragmentations in comet-FISH assay act as in vivo biomarkers of radiation exposure in C57BL/6 and CBA/J mice.

The International Commission on Radiation Protection (ICRP) has lowered the dose limits for workers and for the general public exposed to ionizing radiation. Consequently, a reliable dosimetric method for monitoring possible radiation-induced damage is of great importance in radioprotection. The counting of dicentric chromosomal aberrations and of micronuclei in peripheral blood lymphocytes is unreliable when it is applied to in vivo biopsies and for low-dose exposures.

Two short protein domains are responsible for the nuclear localization of the mouse spermine oxidase mu isoform.

In mouse, at least two catalytically active splice variants (mSMOalpha and mSMOmicro) of the flavin-containing spermine oxidase enzyme are present. We have demonstrated previously that the cytosolic mSMOalpha is the major isoform, while the mSMOmicro enzyme is present in both nuclear and cytoplasmic compartments and has an extra protein domain corresponding to the additional exon VIa. By amino acid sequence comparison and molecular modeling of mSMO proteins, we identified a second domain that is necessary for nuclear localization of the mSMOmicro splice variant.

Mouse spermine oxidase gene splice variants. Nuclear subcellular localization of a novel active isoform.

Spermine oxidase (SMO) is a flavoenzyme involved in polyamine homeostasis in animal cells. The mouse spermine oxidase gene (mSMO) codes for splice variants, including the previously reported major active isoform, herein named alfa (alpha). In the present work, eight additional gene splicing variants were characterized.