scholarly journals Insights into cisplatin-induced neurotoxicity and mitochondrial dysfunction in Caenorhabditis elegans

2021 ◽  
Author(s):  
Carmen Martinez-Fernandez ◽  
Milana Bergamino ◽  
David Brena ◽  
Natascia Ventura ◽  
Sebastian Honnen ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Protective Role ◽  
Automated System ◽  
Dopamine Synthesis ◽  
Physiological Level ◽  
Body Postures ◽  
C Elegans ◽  
Mitochondrial Functions ◽  
Dose Dependent

Cisplatin is the most common drug in first-line chemotherapy against solid tumors. We and others have previously used the nematode Caenorhabditis elegans to identify genetic factors influencing the sensitivity and resistance to cisplatin. In this study, we take advantage of C. elegans to explore cisplatin effects on mitochondrial functions and investigate cisplatin-induced neurotoxicity through a high-resolution semi-automated system for evaluating locomotion. Firstly, we report that a high-glucose diet sensitizes C. elegans to cisplatin at the physiological level and that mitochondrial CED-13 protects the cell from cisplatin-induced oxidative stress. Additionally, by assessing mitochondrial function with a Seahorse Analyzer, we observed a detrimental additive effect of cisplatin and glucose in mitochondrial respiration. Secondly, since we previously found that catechol-O-methyltransferases (involved in dopamine degradation) were upregulated upon cisplatin exposure, we studied the protective role of the FDA-approved drug dopamine against cisplatin-induced neurotoxicity. To implement the use of the Tierpsy Tracker system for measuring neurotoxicity in C. elegans, we showed that abnormal displacements and body postures in cat-2 mutants, which have the dopamine synthesis pathway disrupted, can be rescued by adding dopamine. Then, we used such a system to demonstrate that dopamine treatment protects from the dose-dependent neurotoxicity caused by cisplatin.

scholarly journals Characterization of Caenorhabditis elegans Homologs of the Down Syndrome Candidate Gene DYRK1A

Genetics ◽  
2003 ◽  
Vol 163 (2) ◽  
pp. 571-580 ◽  
Author(s):  
William B Raich ◽  
Celine Moorman ◽  
Clay O Lacefield ◽  
Jonah Lehrer ◽  
Dusan Bartsch ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Caenorhabditis Elegans ◽  
Trisomy 21 ◽  
Gene Dosage ◽  
Inducible Promoters ◽  
C Elegans ◽  
Dual Specificity ◽  
Specificity Protein

Abstract The pathology of trisomy 21/Down syndrome includes cognitive and memory deficits. Increased expression of the dual-specificity protein kinase DYRK1A kinase (DYRK1A) appears to play a significant role in the neuropathology of Down syndrome. To shed light on the cellular role of DYRK1A and related genes we identified three DYRK/minibrain-like genes in the genome sequence of Caenorhabditis elegans, termed mbk-1, mbk-2, and hpk-1. We found these genes to be widely expressed and to localize to distinct subcellular compartments. We isolated deletion alleles in all three genes and show that loss of mbk-1, the gene most closely related to DYRK1A, causes no obvious defects, while another gene, mbk-2, is essential for viability. The overexpression of DYRK1A in Down syndrome led us to examine the effects of overexpression of its C. elegans ortholog mbk-1. We found that animals containing additional copies of the mbk-1 gene display behavioral defects in chemotaxis toward volatile chemoattractants and that the extent of these defects correlates with mbk-1 gene dosage. Using tissue-specific and inducible promoters, we show that additional copies of mbk-1 can impair olfaction cell-autonomously in mature, fully differentiated neurons and that this impairment is reversible. Our results suggest that increased gene dosage of human DYRK1A in trisomy 21 may disrupt the function of fully differentiated neurons and that this disruption is reversible.

A Cuticle Collagen Encoded by the lon-3 Gene May Be a Target of TGF-β Signaling in Determining Caenorhabditis elegans Body Shape

Genetics ◽  
2002 ◽  
Vol 162 (4) ◽  
pp. 1631-1639
Author(s):  
Yo Suzuki ◽  
Gail A Morris ◽  
Min Han ◽  
William B Wood
Keyword(s):  
Caenorhabditis Elegans ◽  
Body Shape ◽  
Small Body ◽  
Dependent Manner ◽  
Loss Of Function ◽  
Cellular Mechanisms ◽  
C Elegans ◽  
Gene Expression Analyses ◽  
Dose Dependent

Abstract The signaling pathway initiated by the TGF-β family member DBL-1 in Caenorhabditis elegans controls body shape in a dose-dependent manner. Loss-of-function (lf) mutations in the dbl-1 gene cause a short, small body (Sma phenotype), whereas overexpression of dbl-1 causes a long body (Lon phenotype). To understand the cellular mechanisms underlying these phenotypes, we have isolated suppressors of the Sma phenotype resulting from a dbl-1(lf) mutation. Two of these suppressors are mutations in the lon-3 gene, of which four additional alleles are known. We show that lon-3 encodes a collagen that is a component of the C. elegans cuticle. Genetic and reporter-gene expression analyses suggest that lon-3 is involved in determination of body shape and is post-transcriptionally regulated by the dbl-1 pathway. These results support the possibility that TGF-β signaling controls C. elegans body shape by regulating cuticle composition.

scholarly journals Small flexible automated system for monitoring Caenorhabditis elegans lifespan based on active vision and image processing techniques

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Joan Carles Puchalt ◽  
Antonio-José Sánchez-Salmerón ◽  
Eugenio Ivorra ◽  
Silvia Llopis ◽  
Roberto Martínez ◽  
...  
Keyword(s):  
Image Processing ◽  
Caenorhabditis Elegans ◽  
Culture Media ◽  
Active Vision ◽  
Automated System ◽  
Rank Test ◽  
P Value ◽  
Vision Systems ◽  
C Elegans ◽  
Processing Techniques

AbstractTraditionally Caenorhabditis elegans lifespan assays are performed by manually inspecting nematodes with a dissection microscope, which involves daily counting of live/dead worms cultured in Petri plates for 21–25 days. This manual inspection requires the screening of hundreds of worms to ensure statistical robustness, and is therefore a time-consuming approach. In recent years, various automated artificial vision systems have been reported to increase the throughput, however they usually provide less accurate results than manual assays. The main problems identified when using these vision systems are the false positives and false negatives, which occur due to culture media changes, occluded zones, dirtiness or condensation of the Petri plates. In this work, we developed and described a new C. elegans monitoring machine, SiViS, which consists of a flexible and compact platform design to analyse C. elegans cultures using the standard Petri plates seeded with E. coli. Our system uses an active vision illumination technique and different image-processing pipelines for motion detection, both previously reported, providing a fully automated image processing pipeline. In addition, this study validated both these methods and the feasibility of the SiViS machine for lifespan experiments by comparing them with manual lifespan assays. Results demonstrated that the automated system yields consistent replicates (p-value log rank test 0.699), and there are no significant differences between automated system assays and traditionally manual assays (p-value 0.637). Finally, although we have focused on the use of SiViS in longevity assays, the system configuration is flexible and can, thus, be adapted to other C. elegans studies such as toxicity, mobility and behaviour.

scholarly journals Interactions between the WEE-1.3 kinase and the PAM-1 aminopeptidase in oocyte maturation and the early C. elegans embryo

2021 ◽  
Author(s):  
Dorothy Benton ◽  
Eva C Jaeger ◽  
Arielle Kilner ◽  
Ashley Kimble ◽  
Josh Lowry ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Oocyte Maturation ◽  
Protective Role ◽  
C Elegans ◽  
Direct Target ◽  
The One ◽  
Actomyosin Cytoskeleton ◽  
Embryonic Viability ◽  
Anterior Posterior

Abstract Puromycin-sensitive aminopeptidases are found across phyla and are known to regulate the cell-cycle and play a protective role in neurodegenerative disease. PAM-1 is a puromycin-sensitive aminopeptidase important for meiotic exit and polarity establishment in the one-cell Caenorhabditis elegans embryo. Despite conservation of this aminopeptidase, little is known about its targets during development. In order to identify novel interactors, we conducted a suppressor screen and isolated four suppressing mutations in three genes that partially rescued the maternal-effect lethality of pam-1 mutants. Suppressed strains show improved embryonic viability and polarization of the anterior-posterior axis. We identified a missense mutation in wee-1.3 in one of these suppressed strains. WEE-1.3 is an inhibitory kinase that regulates maturation promoting factor. While the missense mutation suppressed polarity phenotypes in pam-1, it does so without restoring centrosome-cortical contact or altering the cortical actomyosin cytoskeleton. To see if PAM-1 and WEE-1.3 interact in other processes, we examined oocyte maturation. While depletion of wee-1.3 causes sterility due to precocious oocyte maturation, this effect was lessened in pam-1 worms, suggesting that PAM-1 and WEE-1.3 interact in this process. Levels of WEE-1.3 were comparable between wild-type and pam-1 strains, suggesting that WEE-1.3 is not a direct target of the aminopeptidase. Thus, we have established an interaction between PAM-1 and WEE-1.3 in multiple developmental processes and have identified suppressors that are likely to further our understanding of the role of puromycin-sensitive aminopeptidases during development.

Potential role of protein stabilizers in amelioration of Parkinson's disease and associated effects in transgenic Caenorhabditis elegans model expressing alpha-synuclein

RSC Advances ◽  
2015 ◽  
Vol 5 (95) ◽  
pp. 77706-77715 ◽  
Author(s):  
Supinder Kaur ◽  
Aamir Nazir
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Caenorhabditis Elegans ◽  
Potential Role ◽  
Alpha Synuclein ◽  
C Elegans

Studies employing transgenicC. elegansmodel show that trehalose, a protein stabilizer, alleviates manifestations associated with Parkinson's diseaseviaits inherent activity and through induction of autophagic machinery.

PROTECTIVE ROLE OF FICUS RACEMOSA IN DIABETES INDUCED NEUROPATHY: STRUCTURAL AND FUNCTIONAL EVIDENCES

INDIAN DRUGS ◽  
2017 ◽  
Vol 54 (11) ◽  
pp. 58-60
Author(s):  
N Solanki ◽  
◽  
S. K Bhavsar
Keyword(s):  
Sciatic Nerve ◽  
Diabetic Neuropathy ◽  
Ethanolic Extract ◽  
Protective Role ◽  
Diabetic Rats ◽  
Dependent Manner ◽  
Traditional System ◽  
Ficus Racemosa ◽  
Dose Dependent

Ficus racemosa is used in traditional system of medicine for various health problems and diseases, and is commonly known as Gular fig. The main objective was to study its effects against streptozotocin induced diabetic neuropathy by structural and functional marker. Investigation of diabetic neuropathy was carried out through functional and structural assessment in streptozotocin induced in diabetic rats. Diabetic rats were treated for 28 days in dose dependent manner of Ficus racemosa aqueous extract (250 mg/kg and 500 mg/kg) and ethanolic extract (200 mg/kg and 400 mg/kg). Study showed marked protection observed by Ficus racemosa in hippocampus region of brain and sciatic nerve tissues. Ficus racemosa treatment showed improvement in functional and structural markers, which strongly suggest its protective role in diabetic neuropathy.

scholarly journals Autophagosomes fuse to phagosomes and play important roles in the degradation of apoptotic cells in Caenorhabditis elegans

2021 ◽  
Author(s):  
Omar Pena-Ramos ◽  
Lucia Chiao ◽  
Xianghua Liu ◽  
Tianyou Yao ◽  
Henry He ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Small Gtpase ◽  
Apoptotic Cells ◽  
Phagosome Maturation ◽  
Double Membrane ◽  
C Elegans ◽  
Intracellular Organelles ◽  
Intracellular Vesicles ◽  
Cellular Components

Autophagosomes are double-membrane intracellular vesicles that degrade protein aggregates, intracellular organelles, and other cellular components. In the nematode Caenorhabditis elegans, 113 somatic cells undergo apoptosis during embryogenesis and are engulfed and degraded by their neighboring cells. We discovered a novel role of autophagosomes in facilitating the degradation of apoptotic cells in C. elegans embryos using a real-time imaging technique. Specifically, double-membrane autophagosomes in engulfing cells are recruited to the surfaces of phagosomes containing apoptotic cells and subsequently fuse to phagosomes, allowing the inner membrane to enter the phagosomal lumen. Mutants defective in the production of autophagosomes display significant delays in the degradation of apoptotic cells, demonstrating the important contribution of autophagosomes to this process. The signaling pathway led by the phagocytic receptor CED-1, CED-1s adaptor CED-6, and the large GTPase dynamin (DYN-1) promote the recruitment of autophagosomes to phagosomes. Moreover, the subsequent fusion of autophagosomes with phagosomes requires the functions of the small GTPase RAB-7 and the HOPS complex. Our findings reveal that, unlike the single-membrane, LC3- associated phagocytosis (LAP) vesicles reported for mammalian phagocytes, canonical autophagosomes function in the clearance of C. elegans apoptotic cells. These findings add autophagosomes to the collection of intracellular organelles that contribute to phagosome maturation, identify novel crosstalk between the autophagy and phagosome maturation pathways, and discover the upstream factors that initiate this crosstalk.

scholarly journals Effects of NAD+ in Caenorhabditis elegans Models of Neuronal Damage

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 993
Author(s):  
Yuri Lee ◽  
Hyeseon Jeong ◽  
Kyung Hwan Park ◽  
Kyung Won Kim
Keyword(s):  
Caenorhabditis Elegans ◽  
Therapeutic Strategy ◽  
Axon Regeneration ◽  
Neuronal Damage ◽  
Biological Processes ◽  
Nematode Caenorhabditis Elegans ◽  
C Elegans ◽  
Neuronal Functions ◽  
Molecular Components

Nicotinamide adenine dinucleotide (NAD+) is an essential cofactor that mediates numerous biological processes in all living cells. Multiple NAD+ biosynthetic enzymes and NAD+-consuming enzymes are involved in neuroprotection and axon regeneration. The nematode Caenorhabditis elegans has served as a model to study the neuronal role of NAD+ because many molecular components regulating NAD+ are highly conserved. This review focuses on recent findings using C. elegans models of neuronal damage pertaining to the neuronal functions of NAD+ and its precursors, including a neuroprotective role against excitotoxicity and axon degeneration as well as an inhibitory role in axon regeneration. The regulation of NAD+ levels could be a promising therapeutic strategy to counter many neurodegenerative diseases, as well as neurotoxin-induced and traumatic neuronal damage.

Protective Role of Raphanus Sativus Root Extract on Paracetamol-Induced Hepatotoxicity in Albino Rats

2007 ◽  
Vol 77 (1) ◽  
pp. 41-45 ◽  
Author(s):  
Chaturvedi ◽  
George ◽  
Machacha
Keyword(s):  
Lipid Peroxidation ◽  
Raphanus Sativus ◽  
Thiobarbituric Acid ◽  
Protective Role ◽  
Albino Rats ◽  
Root Extract ◽  
Dependent Manner ◽  
Dose Dependent ◽  
Serum Glutamate

The methanol extract of Raphanus sativus root extract showed a protective effect on paracetamol-induced hepatotoxicity in a dose-dependent manner. Degree of lipid peroxidation caused by paracetamol was measured in terms of thiobarbituric acid reactive substances (TBARS) and protection was measured in reference to serum glutamate oxaloacetate transaminase (SGOT), serum glutamate aspartate transaminase (SGPT), and blood and hepatic levels of antioxidants like glutathione and catalase. Administration of extract along with paracetamol showed significant protection. Levels of TBARS were found to be low, activities of SGOT and SGPT were low, while hepatic glutathione levels were significantly higher in experimental rats that received the mixture of paracetamol and the extract as compared to rats that received paracetamol only. Activities of catalase were also high in all experimental groups. Thus this study indicates the involvement of Raphanus sativus root extract with antioxidants like glutathione and catalase in rendering protection against paracetamol-induced lipid peroxidation and hepatotoxicity.

scholarly journals Aurora-A kinase is required for centrosome maturation in Caenorhabditis elegans

2001 ◽  
Vol 155 (7) ◽  
pp. 1109-1116 ◽  
Author(s):  
Eva Hannak ◽  
Matthew Kirkham ◽  
Anthony A. Hyman ◽  
Karen Oegema
Keyword(s):  
Caenorhabditis Elegans ◽  
Fluorescence Intensity ◽  
Maturation Process ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Wild Type ◽  
C Elegans ◽  
Nuclear Envelope Breakdown ◽  
Pericentriolar Material

Centrosomes mature as cells enter mitosis, accumulating γ-tubulin and other pericentriolar material (PCM) components. This occurs concomitant with an increase in the number of centrosomally organized microtubules (MTs). Here, we use RNA-mediated interference (RNAi) to examine the role of the aurora-A kinase, AIR-1, during centrosome maturation in Caenorhabditis elegans. In air-1(RNAi) embryos, centrosomes separate normally, an event that occurs before maturation in C. elegans. After nuclear envelope breakdown, the separated centrosomes collapse together, and spindle assembly fails. In mitotic air-1(RNAi) embryos, centrosomal α-tubulin fluorescence intensity accumulates to only 40% of wild-type levels, suggesting a defect in the maturation process. Consistent with this hypothesis, we find that AIR-1 is required for the increase in centrosomal γ-tubulin and two other PCM components, ZYG-9 and CeGrip, as embryos enter mitosis. Furthermore, the AIR-1–dependent increase in centrosomal γ-tubulin does not require MTs. These results suggest that aurora-A kinases are required to execute a MT-independent pathway for the recruitment of PCM during centrosome maturation.

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