PD Dr. Ralph Menzel
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Forschungsthemen2
Nematoden als wichtige Quelle für omega-3 langkettige Fettsäuren im Nahrungsnetz des Bodens und die Auswirkungen auf die Ernährung von höheren trophischen Stufen
Quelle ↗Förderer: DFG Eigene Stelle (Sachbeihilfe) Zeitraum: 01/2021 - 01/2024 Projektleitung: PD Dr. Ralph Menzel
Zelluläre Mechanismen und physiologische Funktion von Cytochrom-P450-abhängigen Eicosanoiden am Beispiel des Modellorganismus Caenorhabditis elegans
Quelle ↗Förderer: DFG Eigene Stelle (Sachbeihilfe) Zeitraum: 01/2012 - 12/2014 Projektleitung: PD Dr. Ralph Menzel
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Publikationen25
Top 25 nach Zitationen — Quelle: OpenAlex (BAAI/bge-m3 embedded für Matching).
Dissolved humic substances – ecological driving forces from the individual to the ecosystem level?
2006Freshwater Biology · 274 Zitationen · DOI
Summary 1. This review focuses on direct and indirect interactions between dissolved humic substances (HS) and freshwater organisms and presents novel opinions and hypotheses on their ecological significance. Despite their abundance in freshwaters, the role of HS is still inadequately understood. These substances have been considered too large to be taken up by freshwater organisms. On the contrary, here we present evidence that dissolved HS are indeed taken up and interact directly and/or indirectly with freshwater organisms. 2. We show that dissolved HS exert a mild chemical stress upon aquatic organisms in many ways; they induce molecular chaperones (stress shock proteins), induce and modulate biotransformation enzymes and modulate (mainly inhibiting) the photosynthetic release of oxygen by freshwater plants. Furthermore, they produce an oxidative stress, which may lead to membrane oxidation. HS modulate the multixenobiotic resistance activity and probably other membrane‐bound pumps. This property may lead to the increased bioaccumulation of xenobiotic chemicals. Furthermore, they can modulate the numbers of offspring in a nematode and feminise fish and amphibians. The ecological consequences of this potential remain obscure at present. HS also have the potential to act as chemical attractants (as shown with a nematode). 3. In some macrophytes and algae we show that HS interfere with photosynthesis and growth. For instance, the presence of HS suppresses cyanobacteria more than eukaryotic algae. By applying a quantitative structure activity relationship approach, we show that quinones in the HS interfere with photosynthetic electron transport. We show that even Phragmites leachate can act as a kind of phytotoxin. HS also have the potential to suppress fungal growth, as shown with the water mould Saprolegnia parasitica and force the fungus to respond by spore production. 4. In very soft, humic freshwaters, such as the Rio Negro, Brazil, HS stimulate the uptake of essential ions, such as Na and Ca, at extremely low pH (3.5–4.0) and prevent the ionoregulatory disturbance induced by acid waters, thereby enabling fish to survive in these environments. 5. We discuss whether or not HS are directly utilised by aquatic microorganisms or via exoenzymes, which may be washed in from the terrestrial catchment. There is accumulating evidence that the quality of the HS controls microbial growth. In total, net‐heterotrophy may result from HS‐mediated suppression of primary production by the quinone structures and/or from HS‐mediated support of microbial growth. As there is also evidence that HS have the potential to support photoautotrophic growth and suppress microbial growth, the opposite community effect could result. Consequently, dissolved organic carbon (DOC) has to be chemically characterised, rather than simply measuring bulk DOC concentration. 6. In sum, dissolved HS interact with freshwater organisms in a variety of ways in unenriched humic lakes. In addition to the well known effects of HS on light regime, for example, and the direct and indirect supply with carbon (energy), other interactions may be much more subtle. For instance, HS may induce internal biochemical stress defence systems and have the potential to cause acclimatisation and even adaptation. We are just at the beginning of understanding these interactions between dissolved HS and freshwater organisms.
Biogerontology · 192 Zitationen · DOI
edoc Publication server (Humboldt University of Berlin) · 167 Zitationen · DOI
1.This review focusses on direct and indirect interactions between dissolved humic substances (HS) and freshwater organisms and presents novel opinions and hypotheses on their ecological significance. Despite their abundance in freshwaters, the role of HS is still inadequately understood. These substances have been considered too large to be taken up by freshwater organisms. On the contrary, here we present evidence that dissolved HS are indeed taken up and interact directly and/or indirectly with freshwater organisms. 2.We show that dissolved HS exert a mild chemical stress upon aquatic organisms in many ways; they induce molecular chaperones (stress shock proteins), induce and modulate biotransformation enzymes, and modulate (mainly inhibiting) the photosynthetic release of oxygen by freshwater plants. Furthermore, they produce an oxidative stress, which may lead to membrane oxidation. Humic substances modulate the multixenobiotic resistance activity and, probably, other membrane-bound pumps. This property may lead to the increased bioaccumulation of xenobiotic chemicals. Furthermore, they can modulate the numbers of offspring in a nematode and feminise fish and amphibians. The ecological consequences of this potential remain obscure at present. Humic substances also have the potential to act as chemical attractants (as shown with a nematode). 3.In some macrophytes and algae we show that HS interfere with photosynthesis and growth. For instance, the presence of HS suppresses cyanobacteria more than eukaryotic algae. By applying a quantitative structure activity relationship approach, we show that quinones in the HS interfere with photosynthetic electron transport. We show that even Phragmites leachate can act as a kind of phytotoxin. Humic substances also have the potential to suppress fungal growth, as shown with the water mould Saprolegnia parasitica, and force the fungus to respond by spore production. 4.In very soft, humic freshwaters, such as the Rio Negro, Brazil, HS stimulate the uptake of essential ions, such as Na and Ca, at extremely low pH (3.5–4.0) and prevent the ionoregulatory disturbance induced by acid waters, thereby enabling fish to survive in these environments. 5.We discuss whether or not HS are directly utilised by aquatic microorganisms or via exoenzymes which may by washed in from the terrestrial catchment. There is accumulating evidence that the quality of the HS controls microbial growth. In total, net-heterotrophy may result from HS-mediated suppression of primary production by the quinone structures and/or from HS-mediated support of microbial growth. Since there is also evidence that HS have the potential to support photoautotrophic growth and suppress microbial growth, the opposite community effect could result. Consequently, DOC has to be chemically characterised, rather than simply measuring bulk DOC concentration. 6.In sum, dissolved HS interact with freshwater organisms in a variety of ways in unenriched humic lakes. In addition to the well known effects of HS on light regime, for example, and the direct and indirect supply with carbon (energy), other interactions may be much more subtle. For instance, HS may induce internal biochemical stress defence systems and have the potential to cause acclimatisation and even adaptation. We are just at the beginning of understanding these interactions between dissolved HS and freshwater organisms.
Biogerontology · 161 Zitationen · DOI
Archives of Biochemistry and Biophysics · 159 Zitationen · DOI
Frontiers in Environmental Science · 140 Zitationen · DOI
Microplastics (MP) are pervasive in the environment. There is ample evidence of negative MP effects on biota in aquatic ecosystems, though little is known about MP effects in terrestrial ecosystems. Given numerous entry routes into soils, soil organisms are likely to be exposed to MP. We compared potential toxicological effects of MP from (i) low-density polyethylene (LDPE) (mean diameter ± standard deviation: 57 ± 40 µm) or (ii) a blend of biodegradable polymers polylactide (PLA) and poly(butylene adipate-co-terephthalate) (PBAT) (40 ± 31 µm) on the reproduction and body length of the soil-dwelling bacterivorous nematode Caenorhabditis elegans. Feed suspensions without (control) or with MP (treatments) at concentrations of 1, 10, and 100 mg MP L -1 were prepared and nematodes were exposed to those suspensions on NGM agar plates until completion of their reproductive phase (~ 6 days). Using Nile red-stained PLA/PBAT MP particles and fluorescence microscopy, we demonstrated the ingestion of MP by C. elegans into pharynges and intestines. Under MP exposure, nematodes had fewer offspring (up to 22.9%) compared to nematodes in the control group. This decline was independent on the plastic type. We detected a tendency towards greater decreases in offspring at higher concentrations. Despite hints of negative effects on nematode body length under MP exposure, we could not derive a consistent pattern. We conclude that in MP-contaminated soils, the reproduction of nematodes, central actors in the soil food web, can be affected, with potentially negative implications for key soil functions, e.g., the regulation of soil biogeochemical cycles.
Mechanisms of Ageing and Development · 130 Zitationen · DOI
Humic substances
2007Environmental Science and Pollution Research · 127 Zitationen · DOI
Cell · 125 Zitationen · DOI
The Science of The Total Environment · 118 Zitationen · DOI
Archives of Biochemistry and Biophysics · 115 Zitationen · DOI
Mechanisms of Ageing and Development · 106 Zitationen · DOI
Journal of Natural Products · 104 Zitationen · DOI
The model organism Caenorhabditis elegans was utilized to determine, in vivo, the mode(s) of action of four plant polyphenols, namely, tannic acid (TA), gallic acid (GA), ellagic acid (EA), and catechin (CT). The determination of lifespan, stress resistance, growth, reproduction, eating-related behaviors, antioxidative capacities, and lifespan assays with the mev-1 and the eat-2 mutants as well as in the presence of dead bacteria provided new insights into their action. All four compounds prolonged lifespan, but only TA and CT mediated distinct stress protection. Longevity is unlikely the result of antioxidant capacities but rather due to calorie restriction imitating and hormetic properties in the case of TA and EA or antimicrobial capacities of GA and EA. Furthermore, the prominent "disposable soma theory" is only partly reflected by these polyphenols. In summary, this study underlines the diversity of polyphenolic phytochemicals and their mechanistic background.
Chemosphere · 97 Zitationen · DOI
Cytochrome P450-dependent metabolism of eicosapentaenoic acid in the nematode Caenorhabditis elegans
2008Archives of Biochemistry and Biophysics · 86 Zitationen · DOI
Journal of Molecular Biology · 84 Zitationen · DOI
BMC Genomics · 80 Zitationen · DOI
Abstract Background Traditionally, toxicity of river sediments is assessed using whole sediment tests with benthic organisms. The challenge, however, is the differentiation between multiple effects caused by complex contaminant mixtures and the unspecific toxicity endpoints such as survival, growth or reproduction. The use of gene expression profiling facilitates the identification of transcriptional changes at the molecular level that are specific to the bio-available fraction of pollutants. Results In this pilot study, we exposed the nematode Caenorhabditis elegans to three sediments of German rivers with varying (low, medium and high) levels of heavy metal and organic contamination. Beside chemical analysis, three standard bioassays were performed: reproduction of C. elegans , genotoxicity (Comet assay) and endocrine disruption (YES test). Gene expression was profiled using a whole genome DNA-microarray approach to identify overrepresented functional gene categories and derived cellular processes. Disaccharide and glycogen metabolism were found to be affected, whereas further functional pathways, such as oxidative phosphorylation, ribosome biogenesis, metabolism of xenobiotics, aging and several developmental processes were found to be differentially regulated only in response to the most contaminated sediment. Conclusion This study demonstrates how ecotoxicogenomics can identify transcriptional responses in complex mixture scenarios to distinguish different samples of river sediments.
Environmental Science & Technology · 79 Zitationen · DOI
Humic materials are complex organic molecules constituting the most abundant source of natural organic matter (NOM) in freshwater and soil ecosystems. Recent advances have identified that they interfere with biological systems, via the induction of biotransformation enzymes, the inhibition of photosynthetic oxygen release (in freshwater plants), the production of internal oxidative stress, or through the feminization of fish and amphibians. The nematode model organism Caenorhabditis elegans was chosen to investigate whether a natural and a synthetic humic material induce (i) a behavioral attraction, (ii) the reproduction, and (iii) a response in whole genome transcriptional expression. The phenomenological attractant experiments provided evidence that both humic material sources attract the worm and exert distinct chemical cues. In the reproduction assay, only the highest concentration (32 mg/L DOC of Fuchskuhle NOM, 38 mg/L DOC of HS 1500) resulted in a decrease in brood size, highlighting an overall intrinsic tolerance toward humic material. Finally, oligonucleotide-based whole genome DNA microarray experiments were performed from control and humic material treated worms. Significant transcriptional changes (exceeding a 2-fold increase or decrease) were identified in chemosensors, olfactory receptors, as well as enzymes of the biotransformation system (cytochromes P450, UDP-glucuronosyltransferases, glutathione S-transferases), thereby confirming that humic material is recognized as an environmental signaling chemical.
Hydrobiologia · 70 Zitationen · DOI
Environmental Toxicology and Chemistry · 65 Zitationen · DOI
A ring test was carried out within the standardization process of ISO 10872 to evaluate the precision of the toxicity test for the nematode Caenorhabditis elegans. Eight different laboratories tested aqueous solutions of the reference substance benzylcetyldimethylammonium chloride as well as native sediments and soils for toxic effects on the growth and reproduction of C. elegans. Validity criteria were met in all laboratories. Average median- and low-effect concentrations were determined to be 15.1 mg L(-1) (EC50) and 8.7 mg L(-1) (EC10) for growth and 7.5 mg L(-1) (EC50) and 3.8 mg L(-1) (EC10) for reproduction of C. elegans, with ECx values showing a high degree of reproducibility (CV(R) : <21% and <11% for EC10 and EC50, respectively) and repeatability (CV(r) : <20% and <7% for EC10 and EC50, respectively). The toxic effects of the sediments and soils revealed by the different laboratories were well related to each samples' degree of chemical contamination. Moreover, the effects showed an acceptable reproducibility (CV(R) : 5-33% and 0-28% for growth and reproduction, respectively) and repeatability (CV(r) : 3-13% and 0-12% for growth and reproduction, respectively). The present study confirms that the toxicity test with C. elegans according to ISO 10872 is a reliable and precise tool to assess the toxicity of aqueous media, freshwater sediments, and soils.
The Journals of Gerontology Series A · 63 Zitationen · DOI
This study shows that exposure to low concentrations of the polyphenol tannic acid (TA) induces potent life-prolonging properties in Caenorhabditis elegans. In addition, enhanced thermal stress resistance, reduced growth, and slightly increased oxidative stress resistance were observed, although reproductive capacities and pharyngeal pumping rate were not modulated. Exploiting a suite of 14 mutant strains revealed that the mitogen-activated protein kinase kinase SEK-1 (SAPK/ERK kinase) is a key player involved in TA-mediated longevity. It is conceivable that TA mimics pathogen action and therefore activates the SEK-1-mediated pathogen resistance pathway. This pathway is thought to inhibit potential detrimental effects of TA and may also be involved in the longevity process. The observed dose response suggests the presence of a hormesis effect, and the growth impairment is in agreement with the "Disposable Soma Theory." This report underlines the uniqueness of TA-mediated longevity and facilitates a first glimpse into its complex mode of action.
Yeast · 56 Zitationen · DOI
Overproduction of an endoplasmic reticulum (ER)-resident membrane protein (cytochrome P450 52A3) and of a secretory protein (invertase) was used to study the regulation of the luminal ER protein Kar2p under conditions that lead to ER proliferation and secretory overload, respectively. In both cases we found (i) a significant increase of Kar2 protein and mRNA levels, (ii) a transcriptional regulation based on the the function of the 22 bp unfolded-protein-response element of the KAR2 promoter and (iii) an essential role of the transmembrane kinase Ire1p for upregulation of KAR2 gene expression. These results show that the same mechanism operates when KAR2 induction is triggered by overproduction of cytochrome P450 or invertase and that this mechanism shares the known features of the unfolded-protein-response pathway. Disruption of the IRE1 gene resulted in a marked decrease of the invertase protein levels produced. In contrast, a functional IRE1 gene was not required to reach high-level production of the integral membrane protein cytochrome P450 52A3, Moreover, IRE1 gene disruption did not prevent P450-induced ER proliferation. We suggest that Ire1p-mediated KAR2 induction is, in the case of cytochrome P450 52A3 overproduction, a process which follows on ER proliferation, thereby monitoring the increase of ER size and adjusting the level of Kar2p accordingly.
Yeast · 55 Zitationen · DOI
A full-length cDNA for NADPH-cytochrome P450 reductase from Candida maltosa was cloned and sequenced. The derived amino acid sequence showed a high similarity to the reductases from other eukaryotes. Expression in Saccharomyces cerevisiae under control of the GAL10 promoter resulted in an approximately 70-fold increase in NADPH-cytochrome c reductase activity in the microsomal fraction. The functional integrity of the heterologously expressed reductase as an electron transfer component for alkane hydroxylating cytochrome P450 from C. maltosa was shown in a reconstituted system containing both enzymes in a highly purified state. The signal-anchor sequence of the reductase was identified within the N-terminal region of the protein by means of constructing and expressing fusion proteins with the cytosolic form of yeast invertase. The first 33 amino acids turned out to be sufficient for stable membrane insertion, wild-type membrane orientation and retention in the endoplasmic reticulum. As shown by immunoelectron microscopy, the heterologously expressed reductase was integrated into the endoplasmic reticulum of the host organism. It triggered a strong proliferation of the membrane system. This membrane-inducing property of the reductase was transferable to the cytosolic reporter protein with the same N-terminal sequences that confer membrane insertion.
51 Zitationen
Dissolved humic substances (HSs) are taken up by organisms and interact on various molecular and biochemical levels. With two examples, we show that HSs facilitate fish life in low pH and low calcium waters and promote longevity by mild chemical stress. We re-visit recent papers on fish adaptation in the Amazonian Rio Negro and re-interpret the results on the basis of the recent finding of gene control in the nematode Caenorhabditis elegans. In the nematode, several genes are up-regulated. This may also account for the maintenance of fish life in the Rio Negro. Exposure to HSs exerts mild chemical stress on the exposed organisms and deprives them of energy; however, the nematode C. elegans actively looks for such environments. With life-table and DNA gene filter studies we show that HSs may cause longevity and multiple stress resistance. Furthermore, we propose likely structures of the HSs responsible for these effects. Permanent URL: http://hdl.handle.net/2047/d10010828
Cytochrome P450 Drives a HIF-Regulated Behavioral Response to Reoxygenation by <i>C. elegans</i>
2013Science · 49 Zitationen · DOI
As the Worm Squirms Restoration of oxygen supply to cells that have been deprived of oxygen actually causes further damage to cells and tissues. Such responses, known as reperfusion injury, contribute to the deadly effects of heart attacks and strokes in humans. Lack of oxygen is sensed directly by a prolyl hydroxylase known as EGL-9 in worms and EGLN2 in mammals. Inhibition of EGL-9 can reduce damage caused by reperfusion of tissues with oxygen, but how such beneficial effects are mediated is not clear. Ma et al. (p. 554 , published online 27 June) used a genetic screen in the nematode Caenorhabditis elegans , which has a behavioral response to reoxygenation in which the animals increase their movement, to find factors that interact with EGL-9. They identified the cytochrome p450 oxygenase CYP-13A12 as such a factor. Some cytochrome p450 enzymes act on polyunsaturated fatty acids to make cellular signaling molecules known as eicosanoids. The effects of CYP-13A23 were mediated by eicosanoids. Because the regulatory pathways involved appear to be evolutionarily conserved, the results may aid understanding and management of reperfusion injury in humans.
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- PD Dr. Ralph Menzel
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