Transgenic Manipulation of the Metabolism of Polyamines in Poplar Cells

Bhatnagar, Pratiksha; Glasheen, Bernadette M.; Bains, Suneet K.; Long, Stephanie; Minocha, Rakesh; Walter, Christian; Minocha, Subhash C.

doi:10.1104/pp.125.4.2139

Cited by 105 publications

(111 citation statements)

References 62 publications

(37 reference statements)

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“…33) and visualized under UV illumination. The identification of the polyamines was also confirmed by comigration of the dansylated polyamines with the dansylated standards in a different solvent system (chloroform:triethylamine::5:1) previously reported by Bhatnagar et al (34). Similar separation was obtained with this system also (data not shown).…”

Section: Methodssupporting

confidence: 72%

15-Deoxyspergualin Primarily Targets the Trafficking of Apicoplast Proteins in Plasmodium falciparum

Ramya

Karmodiya

Surolia

et al. 2007

Journal of Biological Chemistry

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15-Deoxyspergualin, an immunosuppressant with tumoricidal and antimalarial properties, has been implicated in the inhibition of a diverse array of cellular processes including polyamine synthesis and protein synthesis. Endeavoring to identify the mechanism of antimalarial action of this molecule, we examined its effect on Plasmodium falciparum protein synthesis, polyamine biosynthesis, and transport. 15-Deoxyspergualin stalled protein synthesis in P. falciparum through Hsp70 sequestration and subsequent phosphorylation of the eukaryotic initiation factor eIF2␣. However, protein synthesis inhibition as well as polyamine depletion were invoked only by high micromolar concentrations of 15-deoxyspergualin, in contrast to the submicromolar concentrations sufficient to inhibit parasite growth. Further investigations demonstrated that 15-deoxyspergualin in the malaria parasite primarily targets the hitherto underexplored process of trafficking of nucleus-encoded proteins to the apicoplast. Our finding that 15-deoxyspergualin kills the malaria parasite by interfering with targeting of nucleus-encoded proteins to the apicoplast not only exposes a chink in the armor of the malaria parasite, but also reveals new realms in our endeavors to study this intriguing biological process. 15-Deoxyspergualin (DSG)4 ( Fig. 1), an analog of spergualin isolated from the culture broth of Bacillus laterosporus, inhibits the growth of the malaria parasite, Plasmodium, in vitro and in vivo, presumably by depleting its polyamine reserves (1, 2). However, other known inhibitors of polyamine biosynthesis, methylglyoxal-bis-(guanylhydrazone) analog (MGBCP), irinotecan hydrochloride (CPT11), and ␣-difluoromethyl ornithine (DFMO) are known to be incapable of suppressing malaria in infected mice (2). This led us to question the speculated mechanism of antimalarial action of DSG.Despite the uncertainty in the actual mechanism of action of DSG, DSG is known to bind cellular chaperones, Hsp70 and Hsp90, potently, via their regulatory C-terminal motif EEVD (3, 4). DSG does not inhibit their chaperone activity (3-5). However, it selectively enhances the ATPase activity of heat shock proteins that have the C-terminal EEVD motif, and this could be the basis of a specific modulation of the function of proteins that bind the EEVD motif of heat shock proteins (5).One of the cellular milieus in which heat shock proteins are speculated to be involved is translational regulation. Translation of an mRNA requires the formation of a ternary complex of the methionyl-tRNA, the mRNA and the 40 S subunit of the ribosome, a feat achieved through the intervention of the GTPbound form of the initiation factor eIF2 (6). Phosphorylation of eIF2␣ at Ser 51 blocks protein synthesis by preventing eIF2 recycling and depleting the cell of its pool of eIF2-GTP required for translation initiation (7). Several conditions of cellular stress trigger the phosphorylation of eIF2␣ via the activation of four different eIF2␣ kinases: PERK (PKR-like endoplasmic reticulum-associated kina...

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Section: Methodssupporting

confidence: 72%

15-Deoxyspergualin Primarily Targets the Trafficking of Apicoplast Proteins in Plasmodium falciparum

Ramya

Karmodiya

Surolia

et al. 2007

Journal of Biological Chemistry

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“…Putrescine accumulation accompanied by reduced or unchanged levels of spermidine and spermine levels has already been observed in oat (Avena sativa) plants subjected to osmotic stress (Tiburcio et al, 1993) and in transgenic Arabidopsis plants overexpressing ADC2 (Alcazar et al, 2005). In this regard, it has been proposed that cellular levels of spermidine and spermine are homeostatically regulated and more tightly than those of putrescine (Bhatnagar et al, 2001). It is possible that the supramolecular organization of aminopropyl transferases (SPDS1, SPDS2, and SPMS) in the form of a metabolon contributes to this regulation (Panicot et al, 2002).…”

Section: Discussionmentioning

confidence: 97%

Putrescine Is Involved in Arabidopsis Freezing Tolerance and Cold Acclimation by Regulating Abscisic Acid Levels in Response to Low Temperature

et al. 2008

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The levels of endogenous polyamines have been shown to increase in plant cells challenged with low temperature; however, the functions of polyamines in the regulation of cold stress responses are unknown. Here, we show that the accumulation of putrescine under cold stress is essential for proper cold acclimation and survival at freezing temperatures because Arabidopsis (Arabidopsis thaliana) mutants defective in putrescine biosynthesis (adc1, adc2) display reduced freezing tolerance compared to wild-type plants. Genes ADC1 and ADC2 show different transcriptional profiles upon cold treatment; however, they show similar and redundant contributions to cold responses in terms of putrescine accumulation kinetics and freezing sensitivity. Our data also demonstrate that detrimental consequences of putrescine depletion during cold stress are due, at least in part, to alterations in the levels of abscisic acid (ABA). Reduced expression of NCED3, a key gene involved in ABA biosynthesis, and down-regulation of ABA-regulated genes are detected in both adc1 and adc2 mutant plants under cold stress. Complementation analysis of adc mutants with ABA and reciprocal complementation tests of the aba2-3 mutant with putrescine support the conclusion that putrescine controls the levels of ABA in response to low temperature by modulating ABA biosynthesis and gene expression.

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“…In transgenic carrot (Daucus carota) and poplar (Populus spp.) cells, these pathways also work independently (Andersen et al, 1998;Bhatnagar et al, 2001). On the other hand, inhibition of PA biosynthesis resulted in cell cycle arrest at the G1 phase, suggesting the involvement of PAs in DNA synthesis (Chattopadhyay et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Sites and Regulation of Polyamine Catabolism in the Tobacco Plant. Correlations with Cell Division/Expansion, Cell Cycle Progression, and Vascular Development

2005

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We previously gave a picture of the homeostatic characteristics of polyamine (PA) biosynthesis and conjugation in tobacco (Nicotiana tabacum) plant organs during development. In this work, we present the sites and regulation of PA catabolism related to cell division/expansion, cell cycle progression, and vascular development in the tobacco plant. Diamine oxidase (DAO), PA oxidase (PAO), peroxidases (POXs), and putrescine N-methyltransferase expressions follow temporally and spatially discrete patterns in shoot apical cells, leaves (apical, peripheral, and central regions), acropetal and basipetal petiole regions, internodes, and young and old roots in developing plants. DAO and PAO produce hydrogen peroxide, a plant signal molecule and substrate for POXs. Gene expression and immunohistochemistry analyses reveal that amine oxidases in developing tobacco tissues precede and overlap with nascent nuclear DNA and also with POXs and lignification. In mature and old tissues, flow cytometry indicates that amine oxidase and POX activities, as well as pao gene and PAO protein levels, coincide with G2 nuclear phase and endoreduplication. In young versus the older roots, amine oxidases and POX expression decrease with parallel inhibition of G2 advance and endoreduplication, whereas putrescine N-methyltransferase dramatically increases. In both hypergeous and hypogeous tissues, DAO and PAO expression occurs in cells destined to undergo lignification, suggesting a different in situ localization. DNA synthesis early in development and the advance in cell cycle/endocycle are temporally and spatially related to PA catabolism and vascular development.Polyamines (PAs) are abundant DNA-and RNAbinding organic cations. They have been correlated with specific roles in embryonic development (Kusunoki and Yasumasu, 1978), carcinogenesis and immune system functions (Seiler et al., 1998), defense (Schroder et al., 1998), antibiotic potency (Petropoulos et al., 2004), cell proliferation and apoptosis (for review, see Wallace et al., 2003;Janne et al., 2004), and in many biotic and abiotic stresses (Jokela et al., 1997;Kurepa et al., 1998;Perez-Amador et al., 2002; for review, see Bouchereau et al., 1999). Investigations on PA physiological functions have been focused mainly on changes in their levels and spectra, leaving the biological significance to be determined. Although genetic analyses have been conducted at the gene level (Laurenzi et al., 1999;Sebela et al., 2001;Rea et al., 2002;Papadakis and Roubelakis-Angelakis, 2005). H 2 O 2 produced by the action of diamine oxidases (DAOs) and PA oxidases (PAOs) can be utilized by POX enzymes in wallstiffening reactions during cell growth and differentiation (Wisniewski et al., 2000). In alkaloid producing plants, such as tobacco (Nicotiana tabacum), putrescine (Put), apart from serving as substrate for spermidine (Spd) biosynthesis or for oxidation (Bagni and Tassoni, 2001), is N-methylated by Put N-methyltransferase (PMT), which catalyzes the first committed steps in the biosynthesis of n...

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Transgenic Manipulation of the Metabolism of Polyamines in Poplar Cells

Cited by 105 publications

References 62 publications

15-Deoxyspergualin Primarily Targets the Trafficking of Apicoplast Proteins in Plasmodium falciparum

15-Deoxyspergualin Primarily Targets the Trafficking of Apicoplast Proteins in Plasmodium falciparum

Putrescine Is Involved in Arabidopsis Freezing Tolerance and Cold Acclimation by Regulating Abscisic Acid Levels in Response to Low Temperature

Sites and Regulation of Polyamine Catabolism in the Tobacco Plant. Correlations with Cell Division/Expansion, Cell Cycle Progression, and Vascular Development

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