Search PubMed⌕ Search

Biomedical subjects

Martin J Mueller

Publications and source records attributed to Martin J Mueller.

At least 19 recordsLinked to original sources

Biologically active oxidized lipids (phytoprostanes) in the plant diet and parenteral lipid nutrition.

Phytoprostanes (PP) are autoxidation products of alpha-linolenate that are present in all plant tissues. Several classes of PP with a prostaglandin (PG) F1-, E1-, A1- and B1-like structure were identified and quantified by gas chromatography-mass spectrometry in vegetable oils and parenteral nutrition (intralipid). High levels of PP (0.09 up to 99 mg/l) were found even in apparently fresh vegetable oils. After oral consumption of olive or soybean oil, PPF1 were absorbed, found to circulate in plasma in conjugated form and excreted in free form into urine. Evidence is emerging that certain PP, such as the PPE1, may modulate the function of immune cells in a PG-like fashion. Here, we show that PPA1- and deoxy-PPJ1 display potent anti-inflammatory and apoptosis inducing activities similar to PGA1 and deoxy-PGJ2. Results of this study indicate that PP are novel, biologically active lipids in plant nutrition.

Adolescent↗

Nonenzymatic lipid peroxidation reprograms gene expression and activates defense markers in Arabidopsis tocopherol-deficient mutants.

Tocopherols (vitamin E) are lipophilic antioxidants that are synthesized by all plants and are particularly abundant in seeds. Two tocopherol-deficient mutant loci in Arabidopsis thaliana were used to examine the functions of tocopherols in seedlings: vitamin e1 (vte1), which accumulates the pathway intermediate 2,3-dimethyl-5-phytyl-1,4-benzoquinone (DMPBQ); and vte2, which lacks all tocopherols and pathway intermediates. Only vte2 displayed severe seedling growth defects, which corresponded with massively increased levels of the major classes of nonenzymatic lipid peroxidation products: hydroxy fatty acids, malondialdehyde, and phytoprostanes. In the absence of pathogens, the phytoalexin camalexin accumulated in vte2 seedlings to levels 100-fold higher than in wild-type or vte1 seedlings. Similarly, gene expression profiling in wild-type, vte1, and vte2 seedlings indicated that increased levels of nonenzymatic lipid peroxidation in vte2 corresponded to increased expression of many defense-related genes, which were not induced in vte1. Both biochemical and transcriptional analyses of vte2 seedlings indicate that nonenzymatic lipid peroxidation plays a significant role in modulating plant defense responses. Together, these results establish that tocopherols in wild-type plants or DMPBQ in vte1 plants limit nonenzymatic lipid peroxidation during germination and early seedling development, thereby preventing the inappropriate activation of transcriptional and biochemical defense responses.

Arabidopsis↗

An integrated view of gene expression and solute profiles of Arabidopsis tumors: a genome-wide approach.

Transformation of plant cells with T-DNA of virulent agrobacteria is one of the most extreme triggers of developmental changes in higher plants. For rapid growth and development of resulting tumors, specific changes in the gene expression profile and metabolic adaptations are required. Increased transport and metabolic fluxes are critical preconditions for growth and tumor development. A functional genomics approach, using the Affymetrix whole genome microarray (approximately 22,800 genes), was applied to measure changes in gene expression. The solute pattern of Arabidopsis thaliana tumors and uninfected plant tissues was compared with the respective gene expression profile. Increased levels of anions, sugars, and amino acids were correlated with changes in the gene expression of specific enzymes and solute transporters. The expression profile of genes pivotal for energy metabolism, such as those involved in photosynthesis, mitochondrial electron transport, and fermentation, suggested that tumors produce C and N compounds heterotrophically and gain energy mainly anaerobically. Thus, understanding of gene-to-metabolite networks in plant tumors promotes the identification of mechanisms that control tumor development.

Arabidopsis↗

Visualization of dynamics of plant-pathogen interaction by novel combination of chlorophyll fluorescence imaging and statistical analysis: differential effects of virulent and avirulent strains of P. syringae and of oxylipins on A. thaliana.

Pathogen infection leads to defence induction as well as to changes in carbohydrate metabolism of plants. Salicylic acid and oxylipins are involved in the induction of defence, but it is not known if these signalling molecules also mediate changes in carbohydrate metabolism. In this study, the effect of application of salicylic acid and the oxylipins 12-oxo-phytodienoic acid (OPDA) and jasmonic acid on photosynthesis was investigated by kinetic chlorophyll fluorescence imaging and compared with the effects of infection by virulent and avirulent strains of Pseudomonas syringae. Both pathogen strains and OPDA caused a similar change in fluorescence parameters of leaves of Arabidopsis thaliana. The response to OPDA appeared faster compared with that to the pathogens and persisted only for a short time. Infiltration with jasmonic acid or salicylic acid did not lead to a localized and distinct fluorescence response of the plant. To capture the faint early symptoms of the plant response, a novel algorithm was applied identifying the unique fluorescence signature-the set of images that, when combined, yield the highest contrast between control and infected leaf segments. Unlike conventional fluorescence parameters, this non-biased approach indeed detected the infection as early as 6 h after inoculation with bacteria. It was posssible to identify distinct fluorescence signatures characterizing the early and late phases of the infection. Fluorescence signatures of both infection phases were found in leaves infiltrated with OPDA.

Arabidopsis↗

Yeast increases resistance in Arabidopsis against Pseudomonas syringae and Botrytis cinerea by salicylic acid-dependent as well as -independent mechanisms.

Cell-wall and glucopeptide components of yeast have been reported to exhibit elicitor activity. The mode of action of defense activation by yeast is not known so far. In this study, we used the model plant Arabidopsis to investigate the activation of defense responses by yeast, the effect on resistance against different pathogens, and the mode of action. Treatment of Arabidopsis plants with an autoclaved yeast suspension induced the expression of systemic acquired resistance-related genes and accumulation of the phytoalexin camalexin. Symptom development and bacterial growth after infection with a virulent strain of the pathogen Pseudomonas syringae was reduced in yeast-pretreated plants. No protection was detectable in mutants affected in the salicylate pathway, while mutants in the jasmonate or camalexin pathway were protected by yeast, indicating that the salicylate pathway is necessary for the yeast-induced resistance against P. syringae. Yeast also reduced symptom development after challenge with Botrytis cinerea. This protection was detectable in all mutants tested, indicating that it is independent of the salicylate, jasmonate, and camalexin pathway.

Arabidopsis↗

Oxylipin analysis methods.

Practical guidelines for monitoring and measuring compounds such as jasmonates, ketols, ketodi(tri)enes and hydroxy-fatty acids as well as detecting the presence of novel oxylipins are presented. Additionally, a protocol for the penetrant analysis of non-enzymatic lipid oxidation is described. Each of the methods, which employ gas chromatography/mass spectrometry, can be applied without specialist knowledge or recourse to the latest analytical instrumentation. Additional information on oxylipin quantification and novel protocols for preparing oxygen isotope-labelled internal standards are provided. Four developing areas of research are identified: (i) profiling of the unbound cellular pools of oxylipins; (ii) profiling of esterified oxylipins and/or monitoring of their release from parent lipids; (iii) monitoring of non-enzymatic lipid oxidation; (iv) analysis of unstable and reactive oxylipins. The methods and protocols presented herein are designed to give technical insights into the first three areas and to provide a platform from which to enter the fourth area.

Esterification↗

Pollen-associated phytoprostanes inhibit dendritic cell interleukin-12 production and augment T helper type 2 cell polarization.

Pollen grains induce allergies in susceptible individuals by release of allergens upon contact with mucosal membranes of the upper respiratory tract. We recently demonstrated that pollen not only function as allergen carriers but also as rich sources of bioactive lipids that attract cells involved in allergic inflammation such as neutrophils and eosinophils. Here we demonstrate that soluble factors from birch (Betula alba L.) pollen activate human dendritic cells (DCs) as documented by phenotypical and functional maturation and altered cytokine production. Betula alba L. aqueous pollen extracts (Bet.-APE) selectively inhibited interleukin (IL)-12 p70 production of lipopolysaccharide (LPS)- or CD40L-activated DC, whereas IL-6, IL-10, and TNFalpha remained unchanged. Presence of Bet.-APE during DC activation resulted in DC with increased T helper type 2 (Th2) cell and reduced Th1 cell polarizing capacity. Chemical analysis of Bet.-APE revealed the presence of phytoprostanes (dinor isoprostanes) with prostaglandin E(1)-, F(1)-, A(1)-, or B(1)-ring systems of which only E(1)-phytoprostanes dose dependently inhibited the LPS-induced IL-12 p70 release and augmented the Th2 cell polarizing capacity of DC. These results suggest that pollen-derived E(1)-phytoprostanes not only resemble endogenous prostaglandin E(2) structurally but also functionally in that they act as regulators that modulate human DC function in a fashion that favors Th2 cell polarization.

Betula↗

Signal signature and transcriptome changes of Arabidopsis during pathogen and insect attack.

Plant defenses against pathogens and insects are regulated differentially by cross-communicating signaling pathways in which salicylic acid (SA), jasmonic acid (JA), and ethylene (ET) play key roles. To understand how plants integrate pathogen- and insect-induced signals into specific defense responses, we monitored the dynamics of SA, JA, and ET signaling in Arabidopsis after attack by a set of microbial pathogens and herbivorous insects with different modes of attack. Arabidopsis plants were exposed to a pathogenic leaf bacterium (Pseudomonas syringae pv. tomato), a pathogenic leaf fungus (Alternaria brassicicola), tissue-chewing caterpillars (Pieris rapae), cell-content-feeding thrips (Frankliniella occidentalis), or phloem-feeding aphids (Myzus persicae). Monitoring the signal signature in each plant-attacker combination showed that the kinetics of SA, JA, and ET production varies greatly in both quantity and timing. Analysis of global gene expression profiles demonstrated that the signal signature characteristic of each Arabidopsis-attacker combination is orchestrated into a surprisingly complex set of transcriptional alterations in which, in all cases, stress-related genes are overrepresented. Comparison of the transcript profiles revealed that consistent changes induced by pathogens and insects with very different modes of attack can show considerable overlap. Of all consistent changes induced by A. brassicicola, Pieris rapae, and E occidentalis, more than 50% also were induced consistently by P. syringae. Notably, although these four attackers all stimulated JA biosynthesis, the majority of the changes in JA-responsive gene expression were attacker specific. All together, our study shows that SA, JA, and ET play a primary role in the orchestration of the plant's defense response, but other regulatory mechanisms, such as pathway cross-talk or additional attacker-induced signals, eventually shape the highly complex attacker-specific defense response.

Alternaria↗

Evaluation of natural and synthetic stimulants of plant immunity by microarray technology.

Induction of local defence, as well as systemic resistance, of plants is associated with transcriptional reprogramming. Here we report on defence gene induction by natural and synthetic stimulants of plant immunity. Gene expression changes in Arabidopsis thaliana were monitored in response to several plant immunity stimulants (plant activators) using Northern blotting and an application-based array representing c. 750 genes involved in several aspects of plant defence and/or plant stress. The commercial plant activators Bio-S, Neudo-Vital and PRORADIX have been shown to induce systemic resistance. Here, Neudo-Vital, PRORADIX and Bio-S treatment induced different patterns of salicylic acid (SA) and jasmonic acid (JA) accumulation. Gene induction by these plant activators proved to be very complex. Rather than simply mimicking one of the known defence pathways induced by SA or JA, the response to the plant activators showed aspects of both major defence systems. A general feature was the transient activation of JA biosynthesis genes, combined with a much more sustained SA-associated defence gene induction. Our results demonstrate that plant immunity stimulants activate systemic immunity at the transcriptional level, and they provide insight into the coordinated transcriptional regulation of several classes of plant defence genes.

Arabidopsis↗

B1-phytoprostanes trigger plant defense and detoxification responses.

Phytoprostanes are prostaglandin/jasmonate-like products of nonenzymatic lipid peroxidation that not only occur ubiquitously in healthy plants but also increase in response to oxidative stress. In this work, we show that the two naturally occurring B(1)-phytoprostanes (PPB(1)) regioisomers I and II (each comprising two enantiomers) are short-lived stress metabolites that display a broad spectrum of biological activities. Gene expression analysis of Arabidopsis (Arabidopsis thaliana) cell cultures treated with PPB(1)-I or -II revealed that both regioisomers triggered a massive detoxification and defense response. Interestingly, expression of several glutathione S-transferases, glycosyl transferases, and putative ATP-binding cassette transporters was found to be increased by one or both PPB(1) regioisomers, and hence, may enhance the plant's capacity to inactivate and sequester reactive products of lipid peroxidation. Moreover, pretreatment of tobacco (Nicotiana tabacum) suspension cells with PPB(1) considerably prevented cell death caused by severe CuSO(4) poisoning. Several Arabidopsis genes induced by PPB(1), such as those coding for adenylylsulfate reductase, tryptophan synthase beta-chain, and PAD3 pointed to an activation of the camalexin biosynthesis pathway that indeed led to the accumulation of camalexin in PPB(1) treated leaves of Arabidopsis. Stimulation of secondary metabolism appears to be a common plant reaction in response to PPB(1). In three different plant species, PPB(1)-II induced a concentration dependent accumulation of phytoalexins that was comparable to that induced by methyl jasmonate. PPB(1)-I was much weaker active or almost inactive. No differences were found between the enantiomers of each regioisomer. Thus, results suggest that PPB(1) represent stress signals that improve plants capacity to cope better with a variety of stresses.

Arabidopsis↗

Light conditions influence specific defence responses in incompatible plant-pathogen interactions: uncoupling systemic resistance from salicylic acid and PR-1 accumulation.

In incompatible plant-pathogen interactions, disease resistance is generated by rapid activation of a multitude of plant defence reactions. Little is known about the dependency of these resistance responses on external factors. The plasticity of plant defence mechanisms in terms of light conditions is studied here. Interaction of Arabidopsis thaliana (L.) Heynh. with an avirulent strain of Pseudomonas syringae pv. maculicola in the dark resulted in increased apoplastic bacterial growth and therefore reduced local resistance as compared to an infection process in the presence of light. Several characteristic defence reactions, including activation of phenylalanine ammonia-lyase, accumulation of salicylic acid (SA), expression of the pathogenesis-related protein PR-1 and the development of a microscopically defined hypersensitive response, proved to be light dependent. In contrast, the extent of the oxidative burst, as estimated by induction of the protectant gene glutathione- S-transferase, was not weakened by the absence of light. Moreover, pathogen-induced accumulation of jasmonic acid, production of the phytoalexin camalexin and transcriptional induction of a pathogen-inducible myrosinase were even more pronounced in the dark. Apart from affecting local defence responses, light also influenced the establishment of systemic acquired resistance (SAR). SAR development in response to infection by avirulent bacteria was completely lost when the primary infection process occurred in the absence of light. SAR developed both under medium (70 micromol photons m(-2) s(-1)) and strong (500 micromol photons m(-2) s(-1)) light conditions but was in the latter case not associated with an accumulation of SA and PR-1 in systemic leaves, demonstrating that SAR can be executed independently from these molecular SAR markers. Our results are consistent with the notion that SA accumulation in infected primary leaves is necessary for induction of systemic resistance and indicate that defence mechanisms different from SA signalling and PR-protein action exist in systemic tissue to confer resistance during SAR.

Arabidopsis↗

Nitric oxide is induced by wounding and influences jasmonic acid signaling in Arabidopsis thaliana.

Nitric oxide (NO) has been associated with plant defense responses during microbial attack, and with induction and/or regulation of programmed cell death. Here, we addressed whether NO participates in wound responses in Arabidopsis thaliana (L.) Heynh. Real-time imaging by confocal laser-scanning microscopy in conjunction with the NO-selective fluorescence indicator 4,5-diaminofluorescein diacetate (DAF-2 DA) uncovered a strong NO burst after wounding or after treatment with JA. The NO burst was triggered within minutes, reminiscent of the oxidative burst during hypersensitive responses. Furthermore, we were able to detect NO in plants (here induced by wounding) by means of electron paramagnetic resonance measurements using diethyldithiocarbamate as a spin trap. When plants were treated with NO, Northern analyses revealed that NO strongly induces key enzymes of jasmonic acid (JA) biosynthesis such as allene oxide synthase (AOS) and lipoxygenase (LOX2). On the other hand, wound-induced AOS gene expression was independent of NO. Furthermore, JA-responsive genes such as defensin (PDF1.2) were not induced, and NO induction of JA-biosynthesis enzymes did not result in elevated levels of JA. However, treatment with NO resulted in accumulation of salicylic acid (SA). In transgenic NahG plants (impaired in SA accumulation and/or signaling), NO did induce JA production and expression of JA-responsive genes. Altogether, the presented data demonstrate that wounding in Arabidopsis induces a fast accumulation of NO, and that NO may be involved in JA-associated defense responses and adjustments.

Arabidopsis↗

The isoprostanoid pathway in plants.

Higher plants are generally unable to synthesize arachidonic acid, and thus, do neither form prostaglandins nor C20-isoprostanes. Instead, plants utilize linolenic acid for the synthesis of prostaglandin-like compounds of the jasmonate type via the lipoxygenase/allene oxide synthase pathway and C18-isoprostanoids, termed phytoprostanes, via a nonenzymatic, free radical catalyzed pathway analogous to the isoprostane pathway in animals. Both pathways are constitutively present in many if not all plants. Formation of jasmonates can be triggered by specific stimuli interacting with membrane receptors while phytoprostane synthesis can be induced by ROS and heavy metals. Jasmonates are established plant signal compounds that induce defense responses including accumulation of antimicrobial secondary metabolites (phytoalexins). Preliminary data indicates that phytoprostanes also induce phytoalexins in a variety of plant species suggesting a possible function of phytoprostanes as mediators of defense reactions in response to oxidative stress in plants.

Diet↗

Archetype signals in plants: the phytoprostanes.

The paradox of aerobic life, or the 'Oxygen Paradox', is that animals and plants cannot exist without oxygen, yet oxygen is inherently dangerous to their existence. The reductive environment of cells provides ample opportunities for oxygen to undergo unscheduled reduction events, yielding free radicals that catalyze lipid peroxidation. Oxidized lipids are constitutively present in higher organisms and, notably, their levels increase in response to a variety of stresses. Recent results suggest that products of non-enzymatic lipid peroxidation pathways, such as the isoprostanes/phytoprostanes in animals and plants, might have an evolutionarily ancient function in host defense.

Animals↗

Cloning and expression of a tomato cDNA encoding a methyl jasmonate cleaving esterase.

Jasmonic acid and its methyl ester are ubiquitous plant signalling compounds necessary for the regulation of growth and development, as well as for the response of plants to environmental stress factors. To date, it is not clear whether methyl jasmonate itself acts as a signal or if its conversion to jasmonic acid is mandatory prior to the induction of a defense response. We have cloned a cDNA, encoding a methyl jasmonate-cleaving enzyme, from tomato cell suspension cultures. Sequence analysis revealed significant similarity to plant esterases and to (S)-hydroxynitrile lyases with an alpha/beta-hydrolase fold structure. The coding sequence was heterologously expressed in Escherichia coli and purified in a catalytically active form. Transcript levels, as well as enzymatic activity, were determined in different tomato tissues. High transcript levels and enzyme activities were found in roots and flowers, while the mRNA level and activity were low in stems and leaves. Moreover, when tested in methyl jasmonate- and elicitor-treated cell suspension cultures, transcript levels were found to decrease, indicating that this particular enzyme might be a regulator of jasmonate signalling.

Acetates↗

Biosynthesis of 14,15-dehydro-12-oxo-phytodienoic acid and related cyclopentenones via the phytoprostane D(1) pathway.

A novel group of cyclopentenone prostaglandin-like compounds, deoxy phytoprostanes J(1), together with their precursors, phytoprostanes D(1), were identified in tobacco, tomato and Arabidopsis. Previously, it was thought that 14,15-dehydro-12-oxo-phytodienoic acid, a member of the deoxy phytoprostanes J(1) family, is derived from either 12-oxo-phytodienoic acid or diketols via the allene oxide synthase pathway. Results suggest that 14,15-dehydro-12-oxo-phytodienoic acid as well as structurally related cyclopentenones of the chromomoric acid family are synthesized via the phytoprostane D(1) pathway in planta. Notably, 14,15-dehydro-12-oxo-phytodienoic acid is more abundant than 12-oxo-phytodienoic acid in all three species so far analyzed.

Arabidopsis↗