Oxidative stress pathways involved in cytotoxicity and genotoxicity of titanium dioxide (TiO2) nanoparticles on cells constitutive of alveolo-capillary barrier in vitro

International audienceThe health risks of nanoparticles remain a serious concern given their prevalence from industrial and domestic use. The primary route of titanium dioxide nanoparticle exposure is inhalation. The extent to which nanoparticles contribute to cellular toxicity is known to associate induction of oxidative stress. To investigate this problem further, the effect of titanium dioxide nanoparticles was examined on cell lines representative of alveolo-capillary barrier. The present study showed that all nanoparticle-exposed cell lines displayed ROS generation. Macrophage-like THP-1 and HPMEC-ST1.6R microvascular cells were sensitive to endogenous redox changes and underwent apoptosis, but not alveolar epithelial A549 cells. Genotoxic potential of titanium dioxide nanoparticles was investigated using the activation of γH2AX, activation of DNA repair proteins and cell cycle arrest. In the sensitive cell lines, DNA damage was persistent and activation of DNA repair pathways was observed. Moreover, western blot analysis showed that specific pathways associated with cellular stress response were activated concomitantly with DNA repair or apoptosis. Nanoparticles-induced oxidative stress is finally signal transducer for further physiological effects including genotoxicity and cytotoxicity. Within activated pathways, HSP27 and SAPK/JNK proteins appeared as potential biomarkers of intracellular stress and of sensitivity to endogenous redox changes, respectively, enabling to predict cell behavior

Quelques enseignements sur les impacts sociaux et économiques de la stratégie de réponse à la pandémie du coronavirus en Belgique

La mise en place du confinement de la population a été efficace pour réduire le nombre de décès et le risque de dépassement des capacités des services de soins. Cependant les mesures restrictives de confinement et de distance ont impacté la société au-delà du plan sanitaire. Dans cet article, nous présentons brièvement quatre travaux de recherche en cours à l’UCLouvain qui relèvent des sciences sociales et des sciences humaines. La première étude relève de la psychologie de la santé et des émotions et montre l’existence de barrières individuelles à adopter les comportements d’hygiène et de distance. La seconde s’appuie sur la recherche en santé mentale et étudie les conséquences du confinement sur la santé mentale des Belges. La troisième relève des sciences du management et des organisations et décrit la capacité de résilience des entreprises face à des situations de crise. Enfin la dernière étude relève du droit et discute de l’importance de la responsabilité collective et de la nécessité de la clarté des règles pour faire respecter les mesures restrictives de liberté

Distinct proteomic and lipidomic composition and atheroprotective functionof human plasma pre-b high-density lipoprotein (HDL)

International audienc

Metabolically Primed Multipotent Hematopoietic Progenitors Fuel Innate Immunity

Following infection, hematopoietic stem and progenitor cells (HSPCs) support immunity by increasing the rate of innate immune cell production but the metabolic cues that guide this process are unknown. To address this question, we developed MetaFate, a method to trace the metabolic expression state and developmental fate of single cells in vivo . Using MetaFate we identified a gene expression program of metabolic enzymes and transporters that confers differences in myeloid differentiation potential in a subset of HSPCs that express CD62L. Using single-cell metabolic profiling, we confirmed that CD62L high myeloid-biased HSPCs have an increased dependency on oxidative phosphorylation and glucose metabolism. Importantly, metabolism actively regulates immune-cell production, with overexpression of the glucose-6-phosphate dehydrogenase enzyme of the pentose phosphate pathway skewing MPP output from B-lymphocytes towards the myeloid lineages, and expansion of CD62L high HSPCs occurring to support emergency myelopoiesis. Collectively, our data reveal the metabolic cues that instruct innate immune cell development, highlighting a key role for the pentose phosphate pathway. More broadly, our results show that HSPC metabolism can be manipulated to alter the cellular composition of the immune system

Phospholipid transfer to high-density lipoprotein (HDL) upon triglyceride lipolysis is directly correlated with HDL-cholesterol levels and is not associated with cardiovascular risk

International audienceBackground and aimsWhile low concentrations of high-density lipoprotein-cholesterol (HDL-C) represent a well-established cardiovascular risk factor, extremely high HDL-C is paradoxically associated with elevated cardiovascular risk, resulting in the U-shape relationship with cardiovascular disease. Free cholesterol transfer to HDL upon lipolysis of triglyceride-rich lipoproteins (TGRL) was recently reported to underlie this relationship, linking HDL-C to triglyceride metabolism and atherosclerosis. In addition to free cholesterol, other surface components of TGRL, primarily phospholipids, are transferred to HDL during lipolysis. It remains indeterminate as to whether such transfer is linked to HDL-C and cardiovascular disease.Methods and resultsWhen TGRL was labelled with fluorescent phospholipid 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI), time- and dose-dependent transfer of DiI to HDL was observed upon incubations with lipoprotein lipase (LPL). The capacity of HDL to acquire DiI was decreased by −36% (p<0.001) in low HDL-C patients with acute myocardial infarction (n = 22) and by -95% (p<0.001) in low HDL-C subjects with Tangier disease (n = 7), unchanged in low HDL-C patients with Type 2 diabetes (n = 17) and in subjects with high HDL-C (n = 20), and elevated in subjects with extremely high HDL-C (+11%, p<0.05) relative to healthy normolipidemic controls. Across all the populations combined, HDL capacity to acquire DiI was directly correlated with HDL-C (r = 0.58, p<0.001). No relationship of HDL capacity to acquire DiI with both overall and cardiovascular mortality obtained from epidemiological studies for the mean HDL-C levels observed in the studied populations was obtained.ConclusionsThese data indicate that the capacity of HDL to acquire phospholipid from TGRL upon LPL-mediated lipolysis is proportional to HDL-C and does not reflect cardiovascular risk in subjects widely differing in HDL-C levels

Free cholesterol transfer to high-density lipoprotein (HDL) upon triglyceride lipolysis underlies the U-shape relationship between HDL-cholesterol and cardiovascular disease

Background: Low concentrations of high-density lipoprotein cholesterol (HDL-C) represent a well-established cardiovascular risk factor. Paradoxically, extremely high HDL-C levels are equally associated with elevated cardiovascular risk, resulting in the U-shape relationship of HDL-C with cardiovascular disease. Mechanisms underlying this association are presently unknown. We hypothesised that the capacity of high-density lipoprotein (HDL) to acquire free cholesterol upon triglyceride-rich lipoprotein (TGRL) lipolysis by lipoprotein lipase underlies the non-linear relationship between HDL-C and cardiovascular risk. Methods: To assess our hypothesis, we developed a novel assay to evaluate the capacity of HDL to acquire free cholesterol (as fluorescent TopFluor® cholesterol) from TGRL upon in vitro lipolysis by lipoprotein lipase. Results: When the assay was applied to several populations markedly differing in plasma HDL-C levels, transfer of free cholesterol was significantly decreased in low HDL-C patients with acute myocardial infarction (−45%) and type 2 diabetes (–25%), and in subjects with extremely high HDL-C of >2.59 mmol/L (>100 mg/dL) (−20%) versus healthy normolipidaemic controls. When these data were combined and plotted against HDL-C concentrations, an inverse U-shape relationship was observed. Consistent with these findings, animal studies revealed that the capacity of HDL to acquire cholesterol upon lipolysis was reduced in low HDL-C apolipoprotein A-I knock-out mice and was negatively correlated with aortic accumulation of [3H]-cholesterol after oral gavage, attesting this functional characteristic as a negative metric of postprandial atherosclerosis. Conclusions: Free cholesterol transfer to HDL upon TGRL lipolysis may underlie the U-shape relationship between HDL-C and cardiovascular disease, linking HDL-C to triglyceride metabolism and atherosclerosis.Fil: Feng, Ma. Inserm; Francia. Université Pierre et Marie Curie; FranciaFil: Darabi, Maryam. Université Pierre et Marie Curie; Francia. Inserm; FranciaFil: Tubeuf, Emilie. Inserm; Francia. Université Pierre et Marie Curie; FranciaFil: Canicio, Aurélie. Université Pierre et Marie Curie; Francia. Inserm; FranciaFil: Lhomme, Marie. Institute Of Cardiometabolism And Nutrition; FranciaFil: Frisdal, Eric. Inserm; Francia. Université Pierre et Marie Curie; FranciaFil: Lanfranchi Lebreton, Sandrine. Université Pierre et Marie Curie; FranciaFil: Matheron, Lucrèce. Université Pierre et Marie Curie; FranciaFil: Rached, Fabiana. Université Pierre et Marie Curie; Francia. Inserm; FranciaFil: Ponnaiah, Maharajah. Institute Of Cardiometabolism And Nutrition; FranciaFil: Serrano, Carlos V.. Instituto Do Coracao Do Hospital Das Clinicas; BrasilFil: Santos, Raul D.. Instituto Do Coracao Do Hospital Das Clinicas; BrasilFil: Brites, Fernando Daniel. Universidad de Buenos Aires; Argentina. Instituto Do Coracao Do Hospital Das Clinicas; BrasilFil: Bolbach, Gerard. Université Pierre et Marie Curie; FranciaFil: Gautier, Emmanuel. Université Pierre et Marie Curie; Francia. Inserm; FranciaFil: Huby, Thierry. Inserm; Francia. Université Pierre et Marie Curie; FranciaFil: Carrie, Alain. Inserm; Francia. Université Pierre et Marie Curie; FranciaFil: Bruckert, Eric. Inserm; Francia. Université Pierre et Marie Curie; FranciaFil: Guerin, Maryse. Université Pierre et Marie Curie; Francia. Inserm; FranciaFil: Couvert, Philippe. Inserm; Francia. Université Pierre et Marie Curie; FranciaFil: Giral, Philippe. Université Pierre et Marie Curie; Francia. Inserm; FranciaFil: Lesnik, Philippe. Université Pierre et Marie Curie; Francia. Inserm; FranciaFil: Le Goff, Wilfried. Université Pierre et Marie Curie; Francia. Inserm; FranciaFil: Guillas, Isabelle. Inserm; Francia. Université Pierre et Marie Curie; FranciaFil: Kontush, Anatol. Inserm; Francia. Université Pierre et Marie Curie; Franci