Dominique Lagadic-Gossmann

Dominique Lagadic-Gossmann
French Institute of Health and Medical Research | Inserm · Research Institute of Health, Environment and Work

PhD, Research director CNRS

About

203
Publications
24,942
Reads
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Introduction
Dominique Lagadic-Gossmann currently works at the Research Institute of Health, Environment and Work, French Institute of Health and Medical Research. She heads the team "Stress, Membrane, Signalling" at IRSET institute. Dominique does research in Environmental Molecular Toxicology. Her current project deals with the impact of environmental pollutants on the energy metabolism of colon cells simulating the colorectal carcinogenesis in link with H+ dynamics.
Additional affiliations
January 2012 - present
Université de Rennes 1
Position
  • Managing Director
Description
  • Deputy director from 01/2012 to 12/2016 - PI of the Inserm team "Stress, Membrane, Signalling" from 01/2017 to present
September 1994 - December 2011
Université de Rennes 1
Position
  • Senior Researcher
Description
  • Director of SeRAIC unit from 01/2008 to 12/2011
October 1992 - August 1994
French National Centre for Scientific Research - Université Paris XI
Position
  • Researcher

Publications

Publications (203)
Article
Full-text available
The prevalence of metabolic diseases, such as obesity, diabetes, metabolic syndrome, and chronic liver diseases among others, has been rising for several years. Epidemiology and mechanistic (in vivo, in vitro and in silico) toxicology have recently provided compelling evidence implicating the chemical environment in the pathogenesis of these diseas...
Article
Full-text available
Non-alcoholic fatty liver disease (NAFLD) is a worldwide epidemic for which environmental contaminants are increasingly recognized as important etiological factors. Among them, the combination of benzo[a]pyrene (B[a]P), a potent environmental carcinogen, with ethanol, was shown to induce the transition of steatosis toward steatohepatitis. However,...
Article
Obesity is a chronic, relapsing condition characterized by excess body fat. Its prevalence has increased globally since the 1970s, and the number of obese and overweight people is now greater than those underweight. Obesity is a multifactorial condition, and as such, many components contribute to its development and pathogenesis. This is the first...
Article
There is increasing evidence of a role for environmental contaminants in disrupting metabolic health in both humans and animals. Despite a growing need for well-understood models for evaluating adipogenic and potential obesogenic contaminants, there has been a reliance on decades-old in vitro models that have not been appropriately managed by cell...
Article
Full-text available
Obesity is a multifactorial disease with both genetic and environmental components. The prevailing view is that obesity results from an imbalance between energy intake and expenditure caused by overeating and insufficient exercise. We describe another environmental element that can alter the balance between energy intake and energy expenditure: obe...
Article
Liver steatosis has been associated with various etiological factors (obesity, alcohol, environmental contaminants). How those factors work together to induce steatosis progression is still scarcely evaluated. Here, we tested whether phthalates could potentiate death of steatotic hepatocytes when combined with ethanol. Pre-steatotic WIF-B9 hepatocy...
Article
A growing body of evidences indicate the major role of extracellular vesicles (EVs) as players of cell communication in the pathogenesis of liver diseases. EVs are membrane-enclosed vesicles released by cells into the extracellular environment. Oxidative stress is also a key component of liver disease pathogenesis, but no role for hepatocyte-derive...
Article
Full-text available
Purpose Several clinical studies suggested that light-to-moderate alcohol intake could alleviate nonalcoholic fatty liver disease (NAFLD), but the underlying mechanism is still poorly understood. Methods Mice fed a high-fat diet (HFD) were submitted or not to moderate ethanol intake for 3 months (ca. 10 g/kg/day) via drinking water. Biochemical, a...
Article
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Marine microalgae are known to be a source of bioactive molecules of interest to human health, such as n-3 polyunsaturated fatty acids (n-3 PUFAs) and carotenoids. The fact that some of these natural compounds are known to exhibit anti-inflammatory, antioxidant, anti-proliferative, and apoptosis-inducing effects, demonstrates their potential use in...
Article
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Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants that can be found in cigarette smoke and contaminated food, the main exposure for non-smokers, and that are considered for some of them as hepatotoxicants. Extracellular vesicles (EVs) are membrane-surrounded nanostructures released by cells into the extracellular environmenta tha...
Article
Microalgae are photosynthetic microorganisms that produce numerous bioactive molecules that can be used as food supplement to prevent chronic disease installation. Indeed, they produce phycobiliproteins, polysaccharides, lipids, carotenoids and sterolic compounds. The use of microalgae in human nutrition provide a mixture of these molecules with sy...
Article
Full-text available
Extracellular vesicles (EVs) are membrane enclosed nanostructures released by cells into the extracellular environment. As major actors of physiological intercellular communication, they have been shown to be pathogenic mediators of several liver diseases. EVs also appear to be potential actors of drug-induced liver injury, but nothing is known con...
Article
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Air pollution is the leading environmental risk factor for disease and premature death in the world. This is mainly due to exposure to urban air particle matter (PM), in particular, fine and ultrafine combustion-derived particles (CDP) from traffic-related air pollution. PM and CDP, including particles from diesel exhaust (DEP), and cigarette smoke...
Article
Despite the improvement of diagnostic methods and anticancer therapeutics, the human population is still facing an increasing incidence of several types of cancers. According to the World Health Organization, this growing trend would be partly linked to our environment, with around 20% of cancers stemming from exposure to environmental contaminants...
Article
Full-text available
Background and Aims: Extracellular vesicles (EVs), membrane enclosed nanostructures released by cells into the extracellular environment, have been described as mediators in several pathogenic processes including liver diseases. In regards to xenobiotic liver injury, EVs emerge as potential actors of DILI (Drug Induced Liver Injury), but nothing i...
Article
Exposure to diesel exhaust particles (DEP) may contribute to endothelial dysfunction and cardiovascular disease. DEP, extractable organic material from DEP (DEP-EOM) and certain PAHs seem to trigger [Ca²⁺]i increase as well as inflammation via GPCRs like βARs and PAR-2. In the present study we explored the involvement of βARs and PAR-2 in effects o...
Article
Résumé L’homéostasie de la membrane plasmique est essentielle à la régulation de plusieurs processus cellulaires comme l’inflammation, la prolifération, la migration ou la mort cellulaire. Cette structure très dynamique peut subir des altérations lors de son exposition à de nombreux toxiques chimiques, déclenchant un signal de stress membranaire, q...
Article
In its classical genomic mode of action, the aryl hydrocarbon receptor (AhR) acts as a ligand activated transcription factor regulating expression of target genes such as CYP1A1 and CYP1B1. Some ligands may also trigger more rapid nongenomic responses through AhR, including calcium signaling (Ca2+). In the present study we observed that pyrene indu...
Article
We previously demonstrated that co-exposing pre-steatotic hepatocytes to benzo[a]pyrene (B[a]P), a carcinogenic environmental pollutant, and ethanol, favored cell death. Here, the intracellular mechanisms underlying this toxicity were studied. Steatotic WIF-B9 hepatocytes, obtained by a 48h-supplementation with fatty acids, were then exposed to B[a...
Article
Full-text available
Exposure to xenobiotics could favor the transition of nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis in obese patients. Recently, we showed in different models of NAFL that benzo[a]pyrene (B[a]P) and ethanol coexposure induced a steatohepatitis-like state. One model was HepaRG cells incubated with stearate and oleate for 2 weeks. I...
Data
The supplementary materials include one table and 6 figures. Supplementary Table 1: primer sequences (5′ to 3′) used for real-time PCR experiments. Supplementary Figure 1: protocol of HepaRG cell culture and treatments. Supplementary Figure 2: long-range PCR for the detection of oxidative mtDNA alterations in nonsteatotic and steatotic HepaRG cells...
Article
Full-text available
The rise in prevalence of non-alcoholic fatty liver disease (NAFLD) constitutes an important public health concern worldwide. Including obesity, numerous risk factors of NAFLD such as benzo[a]pyrene (B[a]P) and ethanol have been identified as modifying the physicochemical properties of the plasma membrane in vitro thus causing membrane remodeling-c...
Article
Full-text available
Background: Exposure to traffic-derived particulate matter (PM), such as diesel exhaust particles (DEP), is a leading environmental cause of cardiovascular disease (CVD), and may contribute to endothelial dysfunction and development of atherosclerosis. It is still debated how DEP and other inhaled PM can contribute to CVD. However, organic chemica...
Article
Full-text available
Exposure to diesel exhaust particles (DEPs) affects endothelial function and may contribute to the development of atherosclerosis and vasomotor dysfunction. As intracellular calcium concentration [Ca2+] i is considered important in myoendothelial signalling, we explored the effects of extractable organic matter from DEPs (DEP-EOM) on [Ca2+] i and m...
Article
Full-text available
Hepatic steatosis (i.e. lipid accumulation) and steatohepatitis have been related to diverse etiologic factors, including alcohol, obesity, environmental pollutants. However, no study has so far analyzed how these different factors might interplay regarding the progression of liver diseases. The impact of the co-exposure to the environmental carcin...
Article
Full-text available
Whereas many phagocytosis steps involve ionic fluxes, the underlying ion channels remain poorly defined. As reported in mice, the calcium conducting TRPV2 channel impacts the phagocytic process. Macrophage phagocytosis is critical for defense against pathogens. In cystic fibrosis (CF), macrophages have lost their capacity to act as suppressor cells...
Article
Full-text available
Most tumors undergo metabolic reprogramming towards glycolysis, the so-called Warburg effect, to support growth and survival. Overexpression of IF1, the physiological inhibitor of the F0F1ATPase, has been related to this phenomenon and appears to be a relevant marker in cancer. Environmental contributions to cancer development are now widely accept...
Article
Beside their crucial role in xenobiotic biotransformation, AhR and Nrf2 are involved in the regulation of energetic metabolism. Nrf2, as a cytoprotective transcription factor, supply energy for detoxification and antioxidant response. AhR is ligand-activated transcriptional factor implicated in several physiological function. Following pollutant ex...
Article
As reported by the World Health Organization, at least 20% of all cancers would be due to environmental agents. However, besides the genotoxic effects of these agents, other cellular and molecular mechanisms would also be involved. In this context, there is still a need to further decipher their precise mode of action. Our previous work showed that...
Article
Full-text available
Exposure to environmental polycyclic aromatic hydrocarbons (PAHs), such as benzo(a)pyrene (B(a)P), has been linked to several health-threatening risks. PAHs were also shown to hinder adrenergic receptor (ADR) responses. As we previously demonstrated that B(a)P can directly interact with the β2ADR, we investigated here whether B(a)P could decrease β...
Article
According to the World Health Organization, around 20% of all cancers would be due to environmental factors. Among these factors, several chemicals are indeed well recognized carcinogens. The widespread contaminant benzo[a]pyrene (B[a]P), an often used model carcinogen of the polycyclic aromatic hydrocarbons’ family, has been suggested to target mo...
Article
The easy-to-use in vivo model, zebrafish larva, is being increasingly used to screen chemical-induced hepatotoxicity, with a good predictivity for various mechanisms of liver injury. However, nothing is known about its applicability in exploring the mechanism called membrane remodeling, depicted as changes in membrane fluidity or lipid raft propert...
Article
Introduction et but de l’étude En France, l’obésité est en constante augmentation et concerne maintenant près d’un individu sur six. Elle est connue pour favoriser le développement d’une stéatose hépatique (accumulation de triglycérides) qui peut, dans 20 % des cas, progresser en stéatohépatite (caractérisée par la mort des hépatocytes et par une i...
Article
Introduction et but de l’étude La stéatose est la pathologie hépatique la plus répandue dans les pays occidentaux, affectant environ 80 % de la population obèse. Elle se caractérise par l’enrichissement des hépatocytes en gouttelettes lipidiques contenant principalement des triglycérides. La stéatose, réversible, est considérée comme bénigne d’un p...
Article
Full-text available
Cancer cells display alterations in many cellular processes. One core hallmark of cancer is the Warburg effect which is a glycolytic reprogramming that allows cells to survive and proliferate. Although the contributions of environmental contaminants to cancer development are widely accepted, the underlying mechanisms have to be clarified. Benzo[a]p...
Article
Full-text available
Transmembrane CD95L (Fas ligand) can be cleaved to release a promigratory soluble ligand, cl-CD95L, which can contribute to chronic inflammation and cancer cell dissemination. The motility signaling pathway elicited by cl-CD95L remains poorly defined. Here, we show that in the presence of cl-CD95L, CD95 activates the Akt and RhoA signaling pathways...
Article
Benzo[a]pyrene (B[a]P), the prototype molecule of polycyclic aromatic hydrocarbons, exhibits genotoxic and carcinogenic effects, which has led the International Agency for Research on Cancer to recognize it as a human carcinogen. Besides the well-known apoptotic signals triggered by B[a]P, survival signals have also been suggested to occur, both si...
Article
Full-text available
Abstract Background: The aryl hydrocarbon receptor (AhR) has gradually emerged as a regulator of inflammation in the lung and other tissues. AhR may interact with the p65-subunit of the nuclear factor (NF)-κB transcription factors, but reported outcomes of AhR/NF-κB-interactions are conflicting. Some studies suggest that AhR possess pro-inflammator...
Article
Nitro-polycyclic aromatic hydrocarbons (nitro-PAHs) are widespread environmental pollutants, generated from reactions between PAHs and nitrogen oxides during combustion processes. In the present study we have investigated the mechanisms of CXCL8 (IL-8) responses induced by 1-nitropyrene (1-NP) in human bronchial epithelial BEAS-2B cells, with focus...
Article
Several epidemiologic studies have shown an interactive effect of heavy smoking and alcohol heavy drinking on the development of hepatocellular carcinoma. It has also been recently described that chronic hepatocyte death can trigger excessive compensatory proliferation resulting later in the formation of tumors in mice liver. As we previously demon...
Conference Paper
Introduction et but de l’étude. – Précédemment, nous avons montre qu’en fonction de leur nature, les acides gras polyinsatures n-3 a longue chaine (omega 3) ont des effets opposes sur la toxicite hepatique de l’ethanol. Ainsi, lors d’une exposition aigue d’hepatocytes de rat en culture primaire par l’ethanol, l’acide docosahexaenoique (DHA, C22:6n-...