scholarly journals Biogenic Amine Neurotransmitters Promote Eicosanoid Production And Protein Homeostasis

2020 ◽  
Author(s):  
Kishore K. Joshi ◽  
Tarmie L. Matlack ◽  
Stephanie Pyonteck ◽  
Ralph Menzel ◽  
Christopher Rongo
Keyword(s):  
Biogenic Amines ◽  
Biogenic Amine ◽  
Ubiquitin Proteasome System ◽  
Cytochrome P450 Monooxygenases ◽  
Protein Homeostasis ◽  
C Elegans ◽  
P450 Monooxygenases ◽  
Eicosanoid Production ◽  
Amine Neurotransmitters ◽  
Multicellular Organisms

ABSTRACTMulticellular organisms use multiple pathways to restore protein homeostasis (proteostasis) in response to adverse physiological conditions, changing environment, and developmental aging. The nervous system can regulate proteostasis in different tissues, but it is unclear how it mobilizes proteostasis pathways to offset physiological decline. Here we show that C. elegans employs the humoral biogenic amine neurotransmitters dopamine, serotonin, and tyramine to regulate proteostasis and the activity of the Ubiquitin Proteasome System (UPS) in epithelial tissues. Mutants for biogenic amine synthesis show decreased poly-ubiquitination and turnover of a GFP-based UPS substrate. Using RNA-seq, we determined the expression profile of genes regulated by biogenic amine signaling. We find that biogenic amines promote the expression of a subset of cytochrome P450 monooxygenases involved in eicosanoid production from polyunsaturated fatty acids (PUFAs). Mutants for these P450s share the same UPS phenotype observed in biogenic amine mutants. The production of n-3 PUFAs is required for UPS substrate turnover, whereas mutants that accumulate n-3 PUFAs show accelerated turnover of this GFP-based substrate. Our results suggest that neurosecretory sensory neurons release biogenic amines to modulate the lipid signaling profile, which in turn activates stress response pathways to maintain proteostasis.

scholarly journals Biogenic amine neurotransmitters promote eicosanoid production and protein homeostasis

EMBO Reports ◽  
2021 ◽  
Author(s):  
Kishore K Joshi ◽  
Tarmie L Matlack ◽  
Stephanie Pyonteck ◽  
Mehul Vora ◽  
Ralph Menzel ◽  
...  
Keyword(s):  
Biogenic Amine ◽  
Protein Homeostasis ◽  
Eicosanoid Production ◽  
Amine Neurotransmitters

scholarly journals Deorphanisation of novel biogenic amine-gated ion channels identifies a new serotonin receptor for learning

2020 ◽  
Author(s):  
Julia Morud ◽  
Iris Hardege ◽  
He Liu ◽  
Taihong Wu ◽  
Swaraj Basu ◽  
...  
Keyword(s):  
Ion Channels ◽  
Biogenic Amine ◽  
Pathogenic Bacteria ◽  
Serotonin Receptor ◽  
Neuronal Function ◽  
Olfactory Conditioning ◽  
C Elegans ◽  
Neuronal Processes ◽  
Amine Neurotransmitters ◽  
Gated Ion Channels

SummaryPentameric ligand-gated ion channels (LGCs) play conserved, critical roles in fast synaptic transmission, and changes in LGC expression and localisation are thought to underlie many forms of learning and memory. The C. elegans genome encodes a large number of LGCs without a known ligand or function. Here, we deorphanize five members of a family of Cys-loop LGCs by characterizing their diverse functional properties that are activated by biogenic amine neurotransmitters. To analyse the neuronal function of these LGCs, we show that a novel serotonin-gated cation channel, LGC-50, is essential for aversive olfactory learning. lgc-50 mutants show a specific defect in learned olfactory avoidance of pathogenic bacteria, a process known to depend on serotonergic neurotransmission. Remarkably, the expression of LGC-50 in neuronal processes is enhanced by olfactory conditioning; thus, the regulated expression of these receptors at synapses appears to represent a molecular cornerstone of the learning mechanism.

scholarly journals The secreted endoribonuclease ENDU-2 from the soma protects germline immortality in C. elegans

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wenjing Qi ◽  
Erika D. V. Gromoff ◽  
Fan Xu ◽  
Qian Zhao ◽  
Wei Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Small Rnas ◽  
C Elegans ◽  
Cleavage Activity ◽  
Response To Temperature ◽  
Multicellular Organisms ◽  
Cell Immortality ◽  
Mature Mrnas ◽  
Endoribonuclease Activity

AbstractMulticellular organisms coordinate tissue specific responses to environmental information via both cell-autonomous and non-autonomous mechanisms. In addition to secreted ligands, recent reports implicated release of small RNAs in regulating gene expression across tissue boundaries. Here, we show that the conserved poly-U specific endoribonuclease ENDU-2 in C. elegans is secreted from the soma and taken-up by the germline to ensure germline immortality at elevated temperature. ENDU-2 binds to mature mRNAs and negatively regulates mRNA abundance both in the soma and the germline. While ENDU-2 promotes RNA decay in the soma directly via its endoribonuclease activity, ENDU-2 prevents misexpression of soma-specific genes in the germline and preserves germline immortality independent of its RNA-cleavage activity. In summary, our results suggest that the secreted RNase ENDU-2 regulates gene expression across tissue boundaries in response to temperature alterations and contributes to maintenance of stem cell immortality, probably via retaining a stem cell specific program of gene expression.

scholarly journals Immunoproteasome Function in Normal and Malignant Hematopoiesis

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1577
Author(s):  
Nuria Tubío-Santamaría ◽  
Frédéric Ebstein ◽  
Florian H. Heidel ◽  
Elke Krüger
Keyword(s):  
Proteasome Inhibition ◽  
Ubiquitin Proteasome System ◽  
Hematologic Malignancies ◽  
Protein Homeostasis ◽  
Efficacy And Safety ◽  
Hematopoietic System ◽  
Oxidized Proteins ◽  
Attractive Therapeutic Target ◽  
Ubiquitin Proteasome ◽  
Early Phases

The ubiquitin–proteasome system (UPS) is a central part of protein homeostasis, degrading not only misfolded or oxidized proteins but also proteins with essential functions. The fact that a healthy hematopoietic system relies on the regulation of protein homeostasis and that alterations in the UPS can lead to malignant transformation makes the UPS an attractive therapeutic target for the treatment of hematologic malignancies. Herein, inhibitors of the proteasome, the last and most important component of the UPS enzymatic cascade, have been approved for the treatment of these malignancies. However, their use has been associated with side effects, drug resistance, and relapse. Inhibitors of the immunoproteasome, a proteasomal variant constitutively expressed in the cells of hematopoietic origin, could potentially overcome the encountered problems of non-selective proteasome inhibition. Immunoproteasome inhibitors have demonstrated their efficacy and safety against inflammatory and autoimmune diseases, even though their development for the treatment of hematologic malignancies is still in the early phases. Various immunoproteasome inhibitors have shown promising preliminary results in pre-clinical studies, and one inhibitor is currently being investigated in clinical trials for the treatment of multiple myeloma. Here, we will review data on immunoproteasome function and inhibition in hematopoietic cells and hematologic cancers.

scholarly journals Activation modes in biocatalytic radical cyclization reactions

2021 ◽  
Author(s):  
Yuxuan Ye ◽  
Haigen Fu ◽  
Todd K Hyster
Keyword(s):  
Heme Iron ◽  
Radical Cyclization ◽  
Cytochrome P450 Monooxygenases ◽  
Radical Cyclizations ◽  
Cyclization Reactions ◽  
Complex Molecules ◽  
P450 Monooxygenases ◽  
Non Heme Iron ◽  
Essential Reactions ◽  
Isopenicillin N

Abstract Radical cyclizations are essential reactions in the biosynthesis of secondary metabolites and the chemical synthesis of societally valuable molecules. In this review, we highlight the general mechanisms utilized in biocatalytic radical cyclizations. We specifically highlight cytochrome P450 monooxygenases (P450s) involved in the biosynthesis of mycocyclosin and vancomycin, non-heme iron- and α-ketoglutarate-dependent dioxygenases (Fe/αKGDs) used in the biosynthesis of kainic acid, scopolamine, and isopenicillin N, and radical S-adenosylmethionine (SAM) enzymes that facilitate the biosynthesis of oxetanocin A, menaquinone, and F420. Beyond natural mechanisms, we also examine repurposed flavin-dependent ‘ene’-reductases (ERED) for non-natural radical cyclization. Overall, these general mechanisms underscore the opportunity for enzymes to augment and enhance the synthesis of complex molecules using radical mechanisms.

Characterization of cytochrome P450-monooxygenases of Chinese hamsters with respect to aflatoxin B1 activation

Toxicology ◽  
1994 ◽  
Vol 93 (2-3) ◽  
pp. 165-173 ◽  
Author(s):  
Morio Fukuhara ◽  
Eric Antignac ◽  
Naomi Fukusen ◽  
Kazue Kato ◽  
Masanobu Kimura
Keyword(s):  
Cytochrome P450 ◽  
Aflatoxin B1 ◽  
Cytochrome P450 Monooxygenases ◽  
P450 Monooxygenases ◽  
Chinese Hamsters

Context-specific regulation of lysosomal lipolysis through network-level diverting of transcription factor interactions

2021 ◽  
Vol 118 (41) ◽  
pp. e2104832118
Author(s):  
Vinod K. Mony ◽  
Anna Drangowska-Way ◽  
Reka Albert ◽  
Emma Harrison ◽  
Abbas Ghaddar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Target Gene ◽  
Specific Nature ◽  
C Elegans ◽  
Functional Interactions ◽  
Genetic Epistasis ◽  
Specific Regulation ◽  
Context Specific ◽  
Factor Interactions ◽  
Multicellular Organisms

Plasticity in multicellular organisms involves signaling pathways converting contexts—either natural environmental challenges or laboratory perturbations—into context-specific changes in gene expression. Congruently, the interactions between the signaling molecules and transcription factors (TF) regulating these responses are also context specific. However, when a target gene responds across contexts, the upstream TF identified in one context is often inferred to regulate it across contexts. Reconciling these stable TF–target gene pair inferences with the context-specific nature of homeostatic responses is therefore needed. The induction of the Caenorhabditis elegans genes lipl-3 and lipl-4 is observed in many genetic contexts and is essential to survival during fasting. We find DAF-16/FOXO mediating lipl-4 induction in all contexts tested; hence, lipl-4 regulation seems context independent and compatible with across-context inferences. In contrast, DAF-16–mediated regulation of lipl-3 is context specific. DAF-16 reduces the induction of lipl-3 during fasting, yet it promotes it during oxidative stress. Through discrete dynamic modeling and genetic epistasis, we define that DAF-16 represses HLH-30/TFEB—the main TF activating lipl-3 during fasting. Contrastingly, DAF-16 activates the stress-responsive TF HSF-1 during oxidative stress, which promotes C. elegans survival through induction of lipl-3. Furthermore, the TF MXL-3 contributes to the dominance of HSF-1 at the expense of HLH-30 during oxidative stress but not during fasting. This study shows how context-specific diverting of functional interactions within a molecular network allows cells to specifically respond to a large number of contexts with a limited number of molecular players, a mode of transcriptional regulation we name “contextualized transcription.”

Detection of Biogenic Amine Producer Bacteria in a Typical Italian Goat Cheese

2008 ◽  
Vol 71 (1) ◽  
pp. 205-209 ◽  
Author(s):  
SILVIA BONETTA ◽  
SARA BONETTA ◽  
ELISABETTA CARRARO ◽  
JEAN DANIEL COÏSSON ◽  
FABIANO TRAVAGLIA ◽  
...  
Keyword(s):  
Biogenic Amines ◽  
Enterococcus Faecalis ◽  
Biogenic Amine ◽  
Pediococcus Acidilactici ◽  
Bacterial Strains ◽  
Goat Cheese ◽  
Low Concentrations ◽  
Amine Content ◽  
High Concentrations ◽  
Almost All

The aim of this study was to research decarboxylating bacterial strains and biogenic amine content in a typical Italian goat cheese (Robiola di Roccaverano). The study was performed on fresh and ripened samples of goat cheese manufactured from industrial and artisanal producers. Sixty-seven bacterial strains isolated showed decarboxylating activity, and Enterococcus faecalis was the most widespread decarboxylating species in all artisanal and industrial products. Pediococcus acidilactici and Enterococcus malodoratus were also identified as biogenic amine producers in Robiola di Roccaverano cheese. All the E. faecalis strains isolated in this study were able to decarboxylate tyrosine. Tyramine was the most abundant biogenic amine in cheese samples, while histamine was the most widespread. High amounts of these two biogenic amines were found in ripened samples (up to 2,067 mg/kg for tyramine and 1,786 mg/kg for histamine), whereas 2-phenylethylamine and tryptamine were present in almost all ripened cheeses at low concentrations. The detection of strains producing biogenic amines and the high concentrations of tyramine and histamine found in ripened Robiola di Roccaverano could represent a potential risk to the consumer.

Sign in / Sign up

Export Citation Format

Share Document