title: Mancozeb affects mitochondrial activity, redox status and ATP production in mouse granulosa cells.
abstract: BACKGROUND
  Mancozeb (MZ) is a fungicide that belongs to the subclass of metal (Mn/Zn) ethylene-bis-dithiocarbamate pesticides. In mouse and human granulosa cells (GCs) exposed to MZ (0.01 μg/ml), morphological modifications and significant alterations of p53 expression level in comparison with control GCs were recorded.
  
  
  OBJECTIVE
  To investigate if MZ (0.01 μg/ml) induces oxidative stress and alters energy metabolism in exposed mouse GCs.
  
  
  RESULTS
  Following fungicide exposure, GCs showed low p53 content, a depolarized mitochondrial membrane potential (ΔΨm), as well as low ATP and reduced glutathione (GSH) levels associated with increased reactive oxygen species (ROS) generation. No remarkable differences on other parameters such as ATP/ADP ratio, energy charge, as well as induction of apoptosis and DNA damage were found. The activation of AKT and PDK1 kinases in MZ-treated cells was observed. Inhibition of ROS generation by the antioxidant N-acetylcysteine (NAC) restored a normal expression level of p53.
  
  
  CONCLUSIONS
  Our results demonstrate that the low dose of MZ here used induces a mild oxidative stress in GCs, and provides evidence for the possible involvement of AKT/PKB signaling pathway in triggering adaptive and survival response.
authors.affiliation: Dept. of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, 67100 L'Aquila, Italy. Electronic address: riorio@cc.univaq.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Iorio
authors.affiliation: Dept. of Life, Health and Environmental Sciences, University of L'Aquila, Via Vetoio, 67100 L'Aquila, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Castellucci
authors.affiliation: Dept. of Life, Health and Environmental Sciences, University of L'Aquila, Via Vetoio, 67100 L'Aquila, Italy.
authors.forename: Gianna
authors.initials: G
authors.lastname: Rossi
authors.affiliation: Dept. of Life, Health and Environmental Sciences, University of L'Aquila, Via Vetoio, 67100 L'Aquila, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Cinque
authors.affiliation: Dept. of Life, Health and Environmental Sciences, University of L'Aquila, Via Vetoio, 67100 L'Aquila, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Cifone
authors.affiliation: Dept. of Life, Health and Environmental Sciences, University of L'Aquila, Via Vetoio, 67100 L'Aquila, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Macchiarelli
authors.affiliation: Dept. of Life, Health and Environmental Sciences, University of L'Aquila, Via Vetoio, 67100 L'Aquila, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Cecconi
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D002478:Cells, Cultured; D004249:DNA Damage; D005260:Female; D005659:Fungicides, Industrial / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism; D008344:Maneb / Q000633:toxicity*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D015038:Zineb / Q000633:toxicity*
chemical_list: D005659:Fungicides, Industrial; D016159:Tumor Suppressor Protein p53; D008344:Maneb; D000255:Adenosine Triphosphate; D051057:Proto-Oncogene Proteins c-akt; D005978:Glutathione; C013099:mancozeb; D015038:Zineb
keywords: AKT kinase; Energy metabolism; Granulosa cells; Mancozeb; Mitochondrial membrane potential; Reactive oxygen species