title: Oxidative stress-induced apoptosis in peripheral blood lymphocytes from patients with POLG-related disorders.
abstract: BACKGROUND
  POLG-related disorders are a group of heterogeneous diseases characterized by an overlapping clinical presentations and associated with mutations in the POLG gene. POLG codes for the catalytic subunit of mitochondrial polymerase gamma (POLG), essential for mitochondrial DNA (mtDNA) replication and repair. Studies on mutator POLG mice showed an increase in oxidative stress and apoptosis. In this regard we analysed the involvement of POLG mutations in the apoptotic regulation, evaluating apoptosis in peripheral blood lymphocytes (PBLs) from patients with POLG-related diseases.
  
  
  METHODS
  Cells were cultured under basal conditions and with 2-deoxy-d-ribose (dRib), a reducing sugar that induces apoptosis by oxidative stress. Apoptosis rate was assessed by flow cytometry. Phosphatidylserine translocation, mitochondrial membrane depolarization and caspase 3 activation were also analysed.
  
  
  RESULTS
  Our data showed higher percentages of apoptosis after dRib treatment in patients with POLG mutations than in controls, while under basal culture conditions, apoptosis levels were similar in the two groups.
  
  
  CONCLUSIONS
  Cells with POLG mutations are more sensitive than control cells to oxidative stress-induced apoptosis, confirming that mtDNA mutations may have a role in mitochondrial apoptosis pathway. We also suggest that redox state homeostasis may play a crucial role in phenotypic expression of POLG-related diseases.
authors.affiliation: Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Formichi
authors.affiliation: Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Radi
authors.affiliation: Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Branca
authors.affiliation: Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Battisti
authors.affiliation: Department of Medical Biotechnologies, University of Siena, Siena, Italy.
authors.forename: Jlenia
authors.initials: J
authors.lastname: Brunetti
authors.affiliation: Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Da Pozzo
authors.affiliation: Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Giannini
authors.affiliation: Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Dotti
authors.affiliation: Department of Medical Biotechnologies, University of Siena, Siena, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Bracci
authors.affiliation: Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy. Electronic address: federico@unisi.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Federico
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics*; D016022:Case-Control Studies; D053148:Caspase 3; D002478:Cells, Cultured; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D003855:Deoxyribose / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D030342:Genetic Diseases, Inborn / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D018384:Oxidative Stress / Q000502:physiology*; D013997:Time Factors
chemical_list: D003855:Deoxyribose; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human; D053148:Caspase 3
keywords: Apoptosis; Mitochondrial polymerase gamma (POLG); Oxidative stress; POLG mutations; POLG-related diseases