title: Nuclear shield: a multi-enzyme task-force for nucleus protection.
abstract: BACKGROUND
  In eukaryotic cells the nuclear envelope isolates and protects DNA from molecules that could damage its structure or interfere with its processing. Moreover, selected protection enzymes and vitamins act as efficient guardians against toxic compounds both in the nucleoplasm and in the cytosol. The observation that a cytosolic detoxifying and antioxidant enzyme i.e. glutathione transferase is accumulated in the perinuclear region of the rat hepatocytes suggests that other unrecognized modalities of nuclear protection may exist. Here we show evidence for the existence of a safeguard enzyme machinery formed by an hyper-crowding of cationic enzymes and proteins encompassing the nuclear membrane and promoted by electrostatic interactions.
  
  
  RESULTS
  Electron spectroscopic imaging, zeta potential measurements, isoelectrofocusing, comet assay and mass spectrometry have been used to characterize this surprising structure that is present in the cells of all rat tissues examined (liver, kidney, heart, lung and brain), and that behaves as a "nuclear shield". In hepatocytes, this hyper-crowding structure is about 300 nm thick, it is mainly formed by cationic enzymes and the local concentration of key protection enzymes, such as glutathione transferase, catalase and glutathione peroxidase is up to seven times higher than in the cytosol. The catalytic activity of these enzymes, when packed in the shield, is not modified and their relative concentrations vary remarkably in different tissues. Removal of this protective shield renders chromosomes more sensitive to damage by oxidative stress. Specific nuclear proteins anchored to the outer nuclear envelope are likely involved in the shield formation and stabilization.
  
  
  CONCLUSIONS
  The characterization of this previously unrecognized nuclear shield in different tissues opens a new interesting scenario for physiological and protection processes in eukaryotic cells. Selection and accumulation of protection enzymes near sensitive targets represents a new safeguard modality which deeply differs from the adaptive response which is based on expression of specific enzymes.
authors.affiliation: Department of Chemical Sciences and Technologies, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Fabrini
authors.forename: Alessio
authors.initials: A
authors.lastname: Bocedi
authors.forename: Valentina
authors.initials: V
authors.lastname: Pallottini
authors.forename: Lorena
authors.initials: L
authors.lastname: Canuti
authors.forename: Michele
authors.initials: M
authors.lastname: De Canio
authors.forename: Andrea
authors.initials: A
authors.lastname: Urbani
authors.forename: Valeria
authors.initials: V
authors.lastname: Marzano
authors.forename: Tommaso
authors.initials: T
authors.lastname: Cornetta
authors.forename: Pasquale
authors.initials: P
authors.lastname: Stano
authors.forename: Anna
authors.initials: A
authors.lastname: Giovanetti
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Stella
authors.forename: Antonella
authors.initials: A
authors.lastname: Canini
authors.forename: Giorgio
authors.initials: G
authors.lastname: Federici
authors.forename: Giorgio
authors.initials: G
authors.lastname: Ricci
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002384:Catalysis; D002412:Cations; D002467:Cell Nucleus / Q000378:metabolism / Q000502:physiology*; D003593:Cytoplasm / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004583:Electrons; D022781:Hepatocytes / Q000166:cytology; D007525:Isoelectric Focusing; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008954:Models, Biological; D051381:Rats; D017208:Rats, Wistar; D055672:Static Electricity; D014018:Tissue Distribution
chemical_list: D000975:Antioxidants; D002412:Cations