Utilization of Mytilus digestive gland cells for the in vitro screening of potential metabolic disruptors in aquatic invertebrates.
In vertebrate systems, many endocrine disruptors (EDs) can also interfere with energy and lipid metabolism, thus acting as metabolic disruptors. At the cellular level, these effects are mainly mediated by interactions with nuclear receptors/transcription factors, leading to the modulation of genes involved in lipid homeostasis, as well as by rapid, receptor-independent pathways. Several potential metabolic disruptors are found in aquatic environments. In fish, different EDs have been shown to affect hepatic lipid homeostasis both in vivo and in vitro. However, little information is available in aquatic invertebrates due to our poor knowledge of the regulatory pathways of lipid metabolism. In this work, primary cell cultures from the digestive gland of the bivalve Mytilus galloprovincialis were utilized to investigate the effects of model EDs (bisphenol A (BPA) and perfluorooctane sulphonate (PFOS)) on lipid homeostasis. Both compounds (at 24 and 3h of exposure) increased intracellular lipid and tryglyceride-TAG content, with strongest effects of PFOS at 10-7M. Acyl-CoA oxidase activity was unaffected, whereas some changes in the activity of glycolytic, antioxidant/biotransformation enzymes were observed; however, no clear relationship was found with lipid accumulation. Evaluation of mitochondrial membrane potential Δψm and determination of extracellular TAG content indicate that PFOS interferes with mitochondrial function and lipid secretion, whereas BPA mainly affects lipid secretion. Experiments with specific inhibitors showed that activation of PI-3 kinase and extracellularly regulated mitogen-activated protein kinase (ERK MAPK) plays a key role in mediating lipid accumulation. Mussel digestive gland cells represent a simple in vitro model for screening the metabolic effects of EDs in marine invertebrates.
Department of Earth, Environment and Life Sciences (DISTAV), University of Genoa, Corso Europa 26, 16132 Genova, Italy.
Teresa
T
Balbi
Department of Earth, Environment and Life Sciences (DISTAV), University of Genoa, Corso Europa 26, 16132 Genova, Italy.
Caterina
C
Ciacci
Department of Earth, Environment and Life Sciences (DISTAV), University of Genoa, Corso Europa 26, 16132 Genova, Italy.
Elena
E
Grasselli
Department of Earth, Environment and Life Sciences (DISTAV), University of Genoa, Corso Europa 26, 16132 Genova, Italy.
Arianna
A
Smerilli
Department of Earth, Environment and Life Sciences (DISTAV), University of Genoa, Corso Europa 26, 16132 Genova, Italy.
Adriana
A
Voci
Department of Earth, Environment and Life Sciences (DISTAV), University of Genoa, Corso Europa 26, 16132 Genova, Italy. Electronic address: Laura.Canesi@unige.it.
Laura
L
Canesi
D017738:Alkanesulfonic Acids / Q000633:toxicity*; D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D002478:Cells, Cultured; D004064:Digestive System / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000633:toxicity*; D004734:Energy Metabolism / Q000187:drug effects*; D004784:Environmental Monitoring / Q000379:methods*; D029941:Fish Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D005466:Fluorocarbons / Q000633:toxicity*; D050356:Lipid Metabolism / Q000187:drug effects*; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D049878:Mytilus / Q000187:drug effects* / Q000378:metabolism; D010636:Phenols / Q000633:toxicity*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D061251:Primary Cell Culture; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D014280:Triglycerides / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D000098826:Bisphenol A Compounds
D017738:Alkanesulfonic Acids; D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D029941:Fish Proteins; D005466:Fluorocarbons; D020928:Mitogen-Activated Protein Kinases; D010636:Phenols; D058539:Phosphatidylinositol 3-Kinase; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D014280:Triglycerides; D014874:Water Pollutants, Chemical; C076994:perfluorooctane sulfonic acid; C006780:bisphenol A; D000098826:Bisphenol A Compounds
Cell signaling; Digestive gland cells; Lipid accumulation; Metabolic disruptors; Mussel