Oxidative stress-induced apoptosis in peripheral blood lymphocytes from patients with POLG-related disorders

Autor: Maria Teresa Dotti, Chiara Branca, Antonio Federico, Elena Radi, Paola Da Pozzo, Patrizia Formichi, Luisa Bracci, Carla Battisti, Fabio Giannini, Jlenia Brunetti
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
Time Factors
Apoptosis
POLG-related diseases
DNA-Directed DNA Polymerase
medicine.disease_cause
0302 clinical medicine
Lymphocytes
Cells
Cultured
chemistry.chemical_classification
Membrane Potential
Mitochondrial
Mutation
Cultured
Caspase 3
Deoxyribose
Middle Aged
Flow Cytometry
POLG mutations
Mitochondrial
DNA Polymerase gamma
Neurology
Genetic Diseases
Female
Adult
Mitochondrial DNA
Mitochondrial polymerase gamma (POLG)
Cells
Oxidative phosphorylation
Biology
Membrane Potential
03 medical and health sciences
medicine
Humans
Oxidative stress
Aged
Case-Control Studies
Genetic Diseases
Inborn
Oxidative Stress
Neurology (clinical)
Reactive oxygen species
Molecular biology
030104 developmental biology
Inborn
Mitochondrial permeability transition pore
chemistry
030217 neurology & neurosurgery
Zdroj: Journal of the neurological sciences. 368
ISSN: 1878-5883
Popis: 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.
Databáze: OpenAIRE
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