The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Takaya Moriguchi - One of the best experts on this subject based on the ideXlab platform.
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Polyamines function in stress tolerance: from synthesis to regulation
Frontiers in plant science, 2015Co-Authors: Ji-hong Liu, Wei Wang, Xiaoqing Gong, Takaya MoriguchiAbstract:Plants are challenged by a variety of biotic or abiotic stresses, which can affect their growth and development, productivity, and geographic distribution. In order to survive adverse environmental conditions, plants have evolved various adaptive strategies, among which is the accumulation of metabolites that play protective roles. A well-established example of the metabolites that are involved in stress responses, or stress tolerance, is the low-molecular-weight aliphatic Polyamines, including putrescine, spermidine, and spermine. The critical role of Polyamines in stress tolerance is suggested by several lines of evidence: firstly, the transcript levels of polyamine biosynthetic genes, as well as the activities of the corresponding enzymes, are induced by stresses; secondly, elevation of endogenous polyamine levels by exogenous supply of Polyamines, or overexpression of polyamine biosynthetic genes, results in enhanced stress tolerance; and thirdly, a reduction of endogenous Polyamines is accompanied by compromised stress tolerance. A number of studies have demonstrated that Polyamines function in stress tolerance largely by modulating the homeostasis of reactive oxygen species (ROS) due to their direct, or indirect, roles in regulating antioxidant systems or suppressing ROS production. The transcriptional regulation of polyamine synthesis by transcription factors is also reviewed here. Meanwhile, future perspectives on polyamine research are also suggested.
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Polyamines and their ability to provide environmental stress tolerance to plants
Plant Biotechnology, 2007Co-Authors: Ji-hong Liu, Hiroyasu Kitashiba, Jing Wang, Yusuke Ban, Takaya MoriguchiAbstract:The present review highlights some recent advances regarding the function of Polyamines in the environmental stress tolerance of plants. When exposed to adverse environmental stresses, such as salt, drought, low temperature, and ozone, the complex dynamic kinetics of polyamine biosynthesis was observed. Polyamines titers altered in different manners dependent upon several factors, such as plant species, tolerance or sensitivity to stress, and duration of stress. The exogenous addition of Polyamines to stress-treated cells or tissues could lead to injury alleviation and growth promotion in most cases, although the effects varied between Polyamines and among plant species. Key genes responsible for polyamine biosynthesis have been cloned from a variety of plant species, whose expressions following stress have been investigated on a molecular basis. Overexpression of the genes caused the modification of polyamine biosynthesis in the transformants coupled with enhancement of stress tolerance. All of these results seem to indicate that Polyamines are an important component in a plant's response to stress and that they play a significant role in counteracting stress.
Anthony E Pegg - One of the best experts on this subject based on the ideXlab platform.
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spermine and spermidine mediate protection against oxidative damage caused by hydrogen peroxide
Amino Acids, 2007Co-Authors: Anthony E Pegg, Patrick M Woster, Robert A Casero, J E Rider, Amy Hacker, Caroline A MackintoshAbstract: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 cells with low levels of predominately spermine or spermidine, spermine appears to be more effective. Importantly, when cells are depleted of both glutathione and endogenous Polyamines, they exhibit increased sensitivity to hydrogen peroxide as compared to glutathione depletion alone, suggesting that Polyamines not only play a role in protecting cells from oxidative stress but this role is distinct from that played by glutathione.
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translational regulation of ornithine decarboxylase and other enzymes of the polyamine pathway
The International Journal of Biochemistry & Cell Biology, 1999Co-Authors: Lisa M Shantz, Anthony E PeggAbstract:Abstract It has long been known that Polyamines play an essential role in the proliferation of mammalian cells, and the polyamine biosynthetic pathway may provide an important target for the development of agents that inhibit carcinogenesis and tumor growth. The rate-limiting enzymes of the polyamine pathway, ornithine decarboxylase (ODC) and S -adenosylmethionine decarboxylase (AdoMetDC), are highly regulated in the cell, and much of this regulation occurs at the level of translation. Although the 5′ leader sequences of ODC and AdoMetDC are both highly structured and contain small internal open reading frames (ORFs), the regulation of their translation appears to be quite different. The translational regulation of ODC is more dependent on secondary structure, and therefore responds to the intracellular availability of active eIF-4E, the cap-binding subunit of the eIF-4F complex, which mediates translation initiation. Cell-specific translation of AdoMetDC appears to be regulated exclusively through the internal ORF, which causes ribosome stalling that is independent of eIF-4E levels and decreases the efficiency with which the downstream ORF encoding AdoMetDC protein is translated. The translation of both ODC and AdoMetDC is negatively regulated by intracellular changes in the Polyamines spermidine and spermine. Thus, when polyamine levels are low, the synthesis of both ODC and AdoMetDC is increased, and an increase in polyamine content causes a corresponding decrease in protein synthesis. However, an increase in active eIF-4E may allow for the synthesis of ODC even in the presence of polyamine levels that repress ODC translation in cells with lower levels of the initiation factor. In contrast, the amino acid sequence that is encoded by the upstream ORF is critical for polyamine regulation of AdoMetDC synthesis, and Polyamines may affect synthesis by interaction with the putative peptide, MAGDIS.
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induction of apoptosis by excessive polyamine accumulation in ornithine decarboxylase overproducing l1210 cells
Biochemical Journal, 1995Co-Authors: Richard Poulin, Georges Pelletier, Anthony E PeggAbstract:Deregulation of polyamine transport in L1210 cells overexpressing ornithine decarboxylase leads to a lethal accumulation of spermidine. We now provide evidence that over-accumulation of natural and synthetic Polyamines, but not putrescine, rapidly induces apoptosis, as shown by hypercondensation of peripheral chromatin and internucleosomal cleavage, followed by nuclear fragmentation. Polyamine oxidation is not responsible for the apoptosis observed. Thus, abnormally high polyamine pools could be an important physiological trigger of apoptosis.
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Polyamines as targets for therapeutic intervention
Annual Review of Pharmacology and Toxicology, 1995Co-Authors: Laurence J Marton, Anthony E PeggAbstract:Polyamines are ubiquitous cell components essential for normal growth. Compounds interfering with polyamine biosynthesis or function have considerable potential for use as therapeutic agents. Inhibitors of ornithine decarboxylase have been shown to be valuable for the treatment of diseases caused by parasitic protozoa, most notably African sleeping sickness. They may also be useful chemopreventive and antineoplastic agents. Inhibitors of S-adenosylmethionine decarboxylase also have potential as treatments of these diseases. Protocols minimizing uptake of exogenous Polyamines via the polyamine-transport system will probably be needed for the full potential of the inhibitors to be realized. Polyamine analogues, notably those with ethyl or benzyl groups on the terminal nitrogen atoms, have potent antiproliferative activity and are promising agents for the treatment of cancer. These analogues are transported by the polyamine-transport system, and their therapeutic effects are less likely to be blocked by the availability of the exogenous Polyamines.
Kazuei Igarashi - One of the best experts on this subject based on the ideXlab platform.
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modulation of protein synthesis by Polyamines
Iubmb Life, 2015Co-Authors: Kazuei Igarashi, Keiko KashiwagiAbstract:Polyamines are ubiquitous small basic molecules that play important roles in cell growth and viability. Since Polyamines mainly exist as a polyamine-RNA complex, we looked for proteins whose synthesis is preferentially stimulated by Polyamines at the level of translation, and thus far identified 17 proteins in Escherichia coli and 6 proteins in eukaryotes. The mechanisms of polyamine stimulation of synthesis of these proteins were investigated. In addition, the role of eIF5A, containing hypusine formed from spermidine, on protein synthesis is described. These results clearly indicate that Polyamines and eIF5A contribute to cell growth and viability through modulation of protein synthesis.
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Polyamines and their metabolites as diagnostic markers of human diseases
Biomolecules & Therapeutics, 2013Co-Authors: Myung Hee Park, Kazuei IgarashiAbstract:Polyamines, putrescine, spermidine and spermine, are ubiquitous in living cells and are essential for eukaryotic cell growth. These polycations interact with negatively charged molecules such as DNA, RNA, acidic proteins and phospholipids and modulate various cellular functions including macromolecular synthesis. Dysregulation of the polyamine pathway leads to pathological conditions including cancer, inflammation, stroke, renal failure and diabetes. Increase in Polyamines and polyamine synthesis enzymes is often associated with tumor growth, and urinary and plasma contents of Polyamines and their metabolites have been investigated as diagnostic markers for cancers. Of these, diacetylated derivatives of spermidine and spermine are elevated in the urine of cancer patients and present potential markers for early detection. Enhanced catabolism of cellular Polyamines by polyamine oxidases (PAO), spermine oxidase (SMO) or acetylpolyamine oxidase (AcPAO), increases cellular oxidative stress and generates hydrogen peroxide and a reactive toxic metabolite, acrolein, which covalently incorporates into lysine residues of cellular proteins. Levels of protein-conjuagated acrolein (PC-Acro) and polyamine oxidizing enzymes were increased in the locus of brain infarction and in plasma in a mouse model of stroke and also in the plasma of stroke patients. When the combined measurements of PC-Acro, interleukin 6 (IL-6), and C-reactive protein (CRP) were evaluated, even silent brain infarction (SBI) was detected with high sensitivity and specificity. Considering that there are no reliable biochemical markers for early stage of stroke, PC-Acro and PAOs present promising markers. Thus the polyamine metabolites in plasma or urine provide useful tools in early diagnosis of cancer and stroke.
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modulation of cellular function by Polyamines
The International Journal of Biochemistry & Cell Biology, 2010Co-Authors: Kazuei Igarashi, Keiko KashiwagiAbstract:Polyamines (putrescine, spermidine and spermine) are essential for normal cell growth. The polyamine levels in cells are regulated by biosynthesis, degradation, and transport. Polyamines can modulate the functions of DNA, nucleotide triphosphates, proteins, and especially RNA because most Polyamines exist in a polyamine-RNA complex in cells. Thus, the major focus on this review is on the role of Polyamines in protein synthesis. In addition, effects of Polyamines on B to Z conversion of DNA, transcription, phosphorylation of proteins, cell cycle progression, apoptosis and ion channels, especially NMDA receptors, are outlined. The function of eIF5A is also briefly discussed. Finally, a correlation between acrolein, produced from Polyamines by polyamine oxidases, and chronic renal failure or brain stroke is summarized. Increased levels of polyamine oxidases and acrolein are good markers of chronic renal failure and brain stroke.
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Decrease in Polyamines with aging and their ingestion from food and drink.
Journal of biochemistry, 2006Co-Authors: Kazuhiro Nishimura, Keiko Kashiwagi, Ritsuko Shiina, Kazuei IgarashiAbstract:Changes in polyamine levels during aging were measured in 3-, 10- and 26-week-old female mice. The level of Polyamines in pancreas, brain, and uterus was maintained during these periods. The level of spermidine slightly decreased in intestine, and decreased significantly in thymus, spleen, ovary, liver, stomach, lung, kidney, heart and muscle during these periods. In skin, the level of spermidine was maximal in 10-week-old mice and markedly reduced in 26-week-old mice. The results suggest that maintenance of polyamine levels may play important roles in the function of the pancreas, brain and uterus in 3- to 26-week-old mice. We next looked for polyamine-rich food materials as a dietary source of Polyamines. Foods found to be rich in Polyamines included wheat germ, rice bran, black rice, Philippine mango, green pepper, Japanese pumpkin, nuts, fermented pickles, pond smelt, turban shell viscera, whelk viscera, salted salmon roe, salted cod roe, beef intestine (boiled) and liver of eel, beef, pork and chicken; and, as previously reported, soybean, fermented soybean (natto), mushrooms, orange and green tea leaf. These results offer useful information when it becomes necessary to ingest Polyamines from food.
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polyamine enhancement of the synthesis of adenylate cyclase at the translational level and the consequential stimulation of the synthesis of the rna polymerase ς28subunit
Journal of Biological Chemistry, 2001Co-Authors: Madoka Yoshida, Keiko Kashiwagi, Gota Kawai, Akira Ishihama, Kazuei IgarashiAbstract:Abstract The effects of Polyamines on the synthesis of various ς subunits of RNA polymerase were studied using Western blot analysis. Synthesis of ς28 was stimulated 4.0-fold and that of ς38 was stimulated 2.3-fold by Polyamines, whereas synthesis of other ς subunits was not influenced by Polyamines. Stimulation of ς28 synthesis was due to an increase in the level of cAMP, which occurred through polyamine stimulation of the synthesis of adenylate cyclase at the level of translation. Polyamines were found to increase the translation of adenylate cyclase mRNA by facilitating the UUG codon-dependent initiation. Analysis of RNA secondary structure suggests that exposure of the Shine-Dalgarno sequence of mRNA is a prerequisite for polyamine stimulation of the UUG codon-dependent initiation.
Ji-hong Liu - One of the best experts on this subject based on the ideXlab platform.
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Polyamines function in stress tolerance: from synthesis to regulation
Frontiers in plant science, 2015Co-Authors: Ji-hong Liu, Wei Wang, Xiaoqing Gong, Takaya MoriguchiAbstract:Plants are challenged by a variety of biotic or abiotic stresses, which can affect their growth and development, productivity, and geographic distribution. In order to survive adverse environmental conditions, plants have evolved various adaptive strategies, among which is the accumulation of metabolites that play protective roles. A well-established example of the metabolites that are involved in stress responses, or stress tolerance, is the low-molecular-weight aliphatic Polyamines, including putrescine, spermidine, and spermine. The critical role of Polyamines in stress tolerance is suggested by several lines of evidence: firstly, the transcript levels of polyamine biosynthetic genes, as well as the activities of the corresponding enzymes, are induced by stresses; secondly, elevation of endogenous polyamine levels by exogenous supply of Polyamines, or overexpression of polyamine biosynthetic genes, results in enhanced stress tolerance; and thirdly, a reduction of endogenous Polyamines is accompanied by compromised stress tolerance. A number of studies have demonstrated that Polyamines function in stress tolerance largely by modulating the homeostasis of reactive oxygen species (ROS) due to their direct, or indirect, roles in regulating antioxidant systems or suppressing ROS production. The transcriptional regulation of polyamine synthesis by transcription factors is also reviewed here. Meanwhile, future perspectives on polyamine research are also suggested.
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involvement of polyamine biosynthesis in somatic embryogenesis of valencia sweet orange citrus sinensis induced by glycerol
Journal of Plant Physiology, 2009Co-Authors: Jing Wang, Ji-hong Liu, Xiuxin DengAbstract:Culture of Citrus sinensis embryogenic callus on the embryo-inducing medium (EIM) containing glycerol gave rise to a large number of embryos, whereas very few embryos were observed on the callus growth medium (CGM). In the current paper, attempts were made to investigate whether polyamine biosynthesis was involved in glycerol-mediated somatic embryogenesis. Quantification of free Polyamines by high-performance liquid chromatography showed that the cultures on EIM had less putrescine than those on CGM. However, increase in spermidine and spermine was detected in cultures on EIM during the first 20d of culture, coincident with abundant somatic embryogenesis. The globular embryos contained more Polyamines than embryos at other stages. Semi-quantitative reverse transcriptase-polymerase chain reaction assay showed that expression levels of all of the five key genes involved in polyamine biosynthesis, with the exception of S-adenosylmethionine decarboxylase, were induced in cultures on EIM, and that their transcriptional levels were increased with maturation of the embryos. Addition of alpha-difluoromethylornithine, a polyamine biosynthesis inhibitor, to EIM resulted in remarkable inhibition of somatic embryogenesis, concurrent with notable reduction of endogenous putrescine and spermidine, particularly at higher concentrations. Exogenous application of 1mM putrescine to EIM together with 5mM alpha-difluoromethylornithine led to dramatic enhancement of endogenous Polyamines, which successfully restored somatic embryogenesis. All of these, collectively, demonstrated that free Polyamines, at least spermidine and spermine herein, were involved in glycerol-mediated promotion of somatic embryogenesis, which will open a new avenue for establishing a sophisticated system for somatic embryogenesis based on the modulation of endogenous Polyamines.
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Polyamines and their ability to provide environmental stress tolerance to plants
Plant Biotechnology, 2007Co-Authors: Ji-hong Liu, Hiroyasu Kitashiba, Jing Wang, Yusuke Ban, Takaya MoriguchiAbstract:The present review highlights some recent advances regarding the function of Polyamines in the environmental stress tolerance of plants. When exposed to adverse environmental stresses, such as salt, drought, low temperature, and ozone, the complex dynamic kinetics of polyamine biosynthesis was observed. Polyamines titers altered in different manners dependent upon several factors, such as plant species, tolerance or sensitivity to stress, and duration of stress. The exogenous addition of Polyamines to stress-treated cells or tissues could lead to injury alleviation and growth promotion in most cases, although the effects varied between Polyamines and among plant species. Key genes responsible for polyamine biosynthesis have been cloned from a variety of plant species, whose expressions following stress have been investigated on a molecular basis. Overexpression of the genes caused the modification of polyamine biosynthesis in the transformants coupled with enhancement of stress tolerance. All of these results seem to indicate that Polyamines are an important component in a plant's response to stress and that they play a significant role in counteracting stress.
Robert A Casero - One of the best experts on this subject based on the ideXlab platform.
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Biochemical evaluation of the anticancer potential of the polyamine-based nanocarrier Nano11047
2017Co-Authors: Tracy Murray-stewart, Laurence J Marton, Elena Ferrari, Ying Xie, David Oupicky, Robert A CaseroAbstract:Synthesizing polycationic polymers directly from existing drugs overcomes the drug-loading limitations often associated with pharmacologically inert nanocarriers. We recently described nanocarriers formed from a first-generation polyamine analogue, bis(ethyl)norspermine (BENSpm), that could simultaneously target polyamine metabolism while delivering therapeutic nucleic acids. In the current study, we describe the synthesis and evaluation of self-immolative nanocarriers derived from the second-generation polyamine analogue PG-11047. Polyamines are absolutely essential for proliferation and their metabolism is frequently dysregulated in cancer. Through its effects on polyamine metabolism, PG-11047 effectively inhibits tumor growth in cancer cell lines of multiple origins as well as in human tumor mouse xenografts. Promising clinical trials have been completed verifying the safety and tolerance of this rotationally restricted polyamine analogue. We therefore used PG-11047 as the basis for Nano11047, a biodegradable, prodrug nanocarrier capable of targeting polyamine metabolism. Following exposure of lung cancer cell lines to Nano11047, uptake and intracellular degradation into the parent compound PG-11047 was observed. The release of PG-11047 highly induced the polyamine catabolic enzyme activities of spermidine/spermine N1-acetyltransferase (SSAT) and spermine oxidase (SMOX). By contrast, the activity of ornithine decarboxylase (ODC), a rate-limiting enzyme in polyamine biosynthesis and a putative oncogene, was decreased. Consequently, intracellular levels of the natural Polyamines were depleted concurrent with tumor cell growth inhibition. This availability of Nano11047 as a novel drug form and potential nucleic acid delivery vector will potentially benefit and encourage future clinical studies.
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Polyamines and cancer implications for chemotherapy and chemoprevention
Expert Reviews in Molecular Medicine, 2013Co-Authors: Shannon L Nowotarski, Patrick M Woster, Robert A CaseroAbstract:Polyamines are small organic cations that are essential for normal cell growth and development in eukaryotes. Under normal physiological conditions, intracellular polyamine concentrations are tightly regulated through a dynamic network of biosynthetic and catabolic enzymes, and a poorly characterised transport system. This precise regulation ensures that the intracellular concentration of Polyamines is maintained within strictly controlled limits. It has frequently been observed that the metabolism of, and the requirement for, Polyamines in tumours is frequently dysregulated. Elevated levels of Polyamines have been associated with breast, colon, lung, prostate and skin cancers, and altered levels of rate-limiting enzymes in both biosynthesis and catabolism have been observed. Based on these observations and the absolute requirement for Polyamines in tumour growth, the polyamine pathway is a rational target for chemoprevention and chemotherapeutics. Here we describe the recent advances made in the polyamine field and focus on the roles of Polyamines and polyamine metabolism in neoplasia through a discussion of the current animal models for the polyamine pathway, chemotherapeutic strategies that target the polyamine pathway, chemotherapeutic clinical trials for polyamine pathway-specific drugs and ongoing clinical trials targeting polyamine biosynthesis.
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spermine and spermidine mediate protection against oxidative damage caused by hydrogen peroxide
Amino Acids, 2007Co-Authors: Anthony E Pegg, Patrick M Woster, Robert A Casero, J E Rider, Amy Hacker, Caroline A MackintoshAbstract: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 cells with low levels of predominately spermine or spermidine, spermine appears to be more effective. Importantly, when cells are depleted of both glutathione and endogenous Polyamines, they exhibit increased sensitivity to hydrogen peroxide as compared to glutathione depletion alone, suggesting that Polyamines not only play a role in protecting cells from oxidative stress but this role is distinct from that played by glutathione.
