Marie-Charlotte Morin

University of Strasbourg; Strasbourg, France

Morin MC et al. (2011) Med Sci (Paris) "[Direct reprogramming: A little worm unveils the cellular transitions]."

Morin MC, Jarriault S

[Med Sci (Paris), 2011]

Sivaranjani M et al. (2016) Int J Food Microbiol "Morin inhibits biofilm production and reduces the virulence of Listeria monocytogenes - An in vitro and in vivo approach."

Ravi AV, Balamurugan K, Kamaladevi A, Sivaranjani M, Pandian SK, Gowrishankar S

[Int J Food Microbiol, 2016]

The current study explores the in vitro and in vivo antibiofilm efficacy of morin against a leading foodborne pathogen-Listeria monocytogenes (LM). Minimum inhibitory concentration (MIC) of morin against LM strains was found to be 100g/ml. The non-antibacterial effect of morin at its sub-MICs (6.25, 12.5 and 25g/ml) was determined through growth curve and XTT assay. Morin at its sub-MICs demonstrated a significant dose dependent inhibitory efficacy against LM biofilm formation which was also evidenced through light, confocal and scanning electron microscopic analyses. However, morin failed to disperse the mature biofilm of LM even at its MIC. Our data also revealed the anti-virulence efficacy of morin, as it significantly inhibited the production of hemolysin and motility of LM. Concentration-dependent susceptibility of morin treated LM cells to normal human serum was observed. In vivo studies revealed that morin extended the lifespan of LM infected Caenorhabditis elegans by about 85%. Furthermore, the non-toxic nature and in vivo anti-adherence efficacy of morin were also ascertained through C. elegans-LM infection model. Overall, the data of the current study identifies morin as a promising antibiofilm agent and its suitability to formulate protective strategies against biofilm associated infections caused by LM.

Frandsen J et al. (2020) ACS Chem Neurosci "Neural Glyoxalase Pathway Enhancement by Morin Derivatives in an Alzheimer's Disease Model."

Frandsen J, Narayanasamy P, Choi SR

[ACS Chem Neurosci, 2020]

The gyloxalase pathway (GP) is an antioxidant defense system that detoxifies metabolic byproduct methylglyoxal (MG). Through sequential reactions, reduced glutathione (GSH), glyoxalase I (glo-1), and glyoxalase II (glo-2) convert MG into D-lactate. Spontaneous reactions involving MG alter the structure and function of cellular macromolecules through the formation of inflammatory advanced glycation endproducts (AGEs). Accumulation of MG and AGEs in neural cells contributes to oxidative stress (OS), a state of elevated inflammation commonly found in neurodegenerative diseases including Alzheimer's Disease (AD). Morin is a common plant-produced flavonoid polyphenol that exhibits the ability to enhance the GP-mediated detoxification of MG. We hypothesize that structural modifications to morin will improve its inherent GP enhancing ability. Here we synthesized a morin derivative, dibromo-morin (DBM) and formulated a morin encapsulated nanoparticle (MNP) - and examined their efficacy in enhancing neural GP activity. Cultured mouse primary cerebellar neurons and Caenorhabditis elegans were induced to a state of OS with MG, and treated with morin, DBM, and MNP. Results indicated the morin derivatives were more effective compared to the parent compound in neural GP enhancement and preventing MG-mediated OS.

Picture from Padmanabhan S et al. (2009) Cell "A PP2A regulatory subunit regulates C. elegans insulin/IGF-1 signaling by ...."

Figure 3. PPTR-1 Colocalizes with AKT-1. akt-1::gfp;pptr-1::mC-flag, akt-2::gfp;pptr-1::mC-flag, and sgk-1::gfp;pptr-1::mC-flag transgenic worms were mounted and visualized by fluorescence microscopy with Rhodamine (mCherry) and FITC (GFP) filters. PPTR-1 expression is observed mainly in the pharynx, vulva, and spermatheca ([A]-[C], mCherry).(A) Expression of PPTR-1::mC-FLAG (mCherry) and AKT-1::GFP (GFP) in a akt-1::gfp; pptr-1::mC-flag strain. Expression of PPTR-1::mC-FLAG overlaps with AKT-1::GFP (Merge).(B) PPTR-1::mC-FLAG and AKT-2::GFP colocalize in some tissues in a akt-2::gfp; pptr-1::mC-flag strain (Merge).(C) SGK-1::GFP and PPTR-1::mC-FLAG do not colocalize in sgk-1::gfp;pptr-1::mC-flag transgenic worms (Merge).Arrows indicate the following tissues: p, pharynx; v, vulva; s, spermatheca; i, intestine.

Qu M et al. (2019) Ecotoxicol Environ Saf "Nanopolystyrene at predicted environmental concentration enhances microcystin-LR toxicity by inducing intestinal damage in Caenorhabditis elegans."

Nida A, Wang D, Kong Y, Qu M, Du H, Xiao G

[Ecotoxicol Environ Saf, 2019]

We employed nematode Caenorhabditis elegans to determine the combinational effect between nanopolystyrene at predicted environmental concentration and microcystin-LR (MC-LR). Prolonged exposure to nanopolystyrene (1g/L) increased MC-LR (0.1g/L) toxicity in reducing brood size and locomotion behavior and in inducing oxidative stress. Moreover, the adsorption of MC-LR by nanopolystyrene particles played an important role in inducing the enhancement in MC-LR toxicity by nanopolystyrene particles. Additionally, only exposure to resuspension of nanopolystyrene (1g/L) caused the increased intestinal permeability in MC-LR (0.1g/L) exposed nematodes. Our data indicates the potential of nanopolystyrene at predicted environmental concentration in enhancing MC-LR toxicity on environmental organisms.

Li Y et al. (2009) J Environ Sci (China) "Using the nematode Caenorhabditis elegans as a model animal for assessing the toxicity induced by microcystin-LR."

Pu Y, Wang D, Yin L, Li Y, Wang Y

[J Environ Sci (China), 2009]

Among more than 75 variants of microcystin (MC), microcystin-LR (MC-LR) is one of the most common toxins. In this study, the feasibility of using Caenorhabditis elegans to evaluate MC-LR toxicity was studied. C. elegans was treated with MC-LR at different concentrations ranging from 0.1 to 80 Ig/L. The results showed that MC-LR could reduce lifespan, delay development, lengthen generation time, decrease brood size, suppress locomotion behavior, and decreases hsp-16-2-gfp expression. The endpoints of generation time, brood size, and percentage of the population expressing hsp-16-2-gfp were very sensitive to 1.0 microg/L of MC-LR, and would be more useful for the evaluation of MC-LR toxicity. Furthermore, the tissue-specific hsp-16-2-gfp expressions were investigated in MC-LR-exposed animals, and the nervous system and intestine were primarily affected by MC-LR. Therefore, the generation time, brood size, and hsp-16-2-gfp expression in C. elegans can be explored to serve as valuable endpoints for evaluating the potential toxicity from MC-LR exposure.

Picture from Ao W et al. (2004) Science "Environmentally induced foregut remodeling by PHA-4/FoxA and ...."

C15H9.9 is expressed in Ph-MC. Dotted lines indicate the pharynx.

Microcystin-LR : unc-30

The expression levels of unc-30 gene showed a significant decrease on 0.1 g/1 of MC-LR (p<0.01) and more than 1 g/1 of MC-LR (p<0.01).

Zhan C et al. (2024) Toxins (Basel) "Mutations at Two Key Sites in PP2A Safeguard Caenorhabditis elegans Neurons from Microcystin-LR Toxicity."

Zhan C, Gong J

[Toxins (Basel), 2024]

Microcystin-LR (MC-LR) is a secondary metabolite produced by cyanobacteria, globally renowned for its potent hepatotoxicity. However, an increasing body of research suggests that it also exhibits pronounced neurotoxicity. PP2A is a fundamental intracellular phosphatase that plays a pivotal role in cell development and survival. Although extensive research has focused on the binding of MC-LR to the C subunit of PP2A, few studies have explored the key amino acid sites that can prevent the binding of MC-LR to PP2A-C. Due to the advantages of <i>Caenorhabditis elegans</i> (<i>C. elegans</i>), such as ease of genetic editing and a short lifespan, we exposed nematodes to MC-LR in a manner that simulated natural exposure conditions based on MC-LR concentrations in natural water bodies (immersion exposure). Our findings demonstrate that MC-LR exerts comprehensive toxicity on nematodes, including reducing lifespan, impairing reproductive capabilities, and diminishing sensory functions. Notably, and for the first time, we observed that MC-LR neurotoxic effects can persist up to the F3 generation, highlighting the significant threat that MC-LR poses to biological populations in natural environments. Furthermore, we identified two amino acid sites (L252 and C278) in PP2A-C through mutations that prevented MC-LR binding without affecting PP2A activity. This discovery was robustly validated through behavioral studies and neuronal calcium imaging using nematodes. In conclusion, we identified two crucial amino acid sites that could prevent MC-LR from binding to PP2A-C, which holds great significance for the future development of MC-LR detoxification drugs.