Respective effects of oxygen and energy substrate deprivation on beta cell viability

Autor: Marie-Jeanne Richard, Laurent Argaud, Sandrine Lablanche, Cécile Cottet-Rousselle, Thierry Berney, Pierre-Yves Benhamou, Camille Laporte, Eric Fontaine, Frédéric Lamarche
Přispěvatelé: Centre Hospitalier Universitaire [Grenoble] (CHU), Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Rok vydání: 2015
Předmět:
[SDV]Life Sciences [q-bio]
Apoptosis
medicine.disease_cause
Mitochondrial Membrane Transport Proteins
environment and public health
Biochemistry
Oxygen/*pharmacology
Energy Metabolism/drug effects
chemistry.chemical_compound
Anoxia
Metformin/pharmacology
Cyclosporin a
Hypoxia
Cells
Cultured
Microscopy
Cultured
Microscopy
Confocal
geography.geographical_feature_category
ddc:617
Superoxide
Free Radical Scavengers
Apoptosis/*drug effects
Flow Cytometry
Islet
Metformin
Mitochondria
Cell biology
Beta cell
Confocal
Free Radical Scavengers/pharmacology
Mitochondrial Membrane Transport Proteins/*drug effects
Programmed cell death
medicine.medical_specialty
Ischemia–reperfusion injury
Cells
Oxidative Stress/drug effects
Mitochondria/*drug effects/metabolism
Biophysics
Islets of Langerhans/*drug effects/*metabolism/pathology
Biology
Acetylcysteine/pharmacology
Permeability transition
Hypoglycemic Agents/pharmacology
Islets of Langerhans
Reactive Oxygen Species/metabolism
Internal medicine
medicine
Animals
Humans
Hypoglycemic Agents
geography
Mitochondrial Permeability Transition Pore
Cell Biology
Acetylcysteine
Rats
Oxygen
Transplantation
Oxidative Stress
enzymes and coenzymes (carbohydrates)
Endocrinology
chemistry
Energy Metabolism
Reactive Oxygen Species
Oxidative stress
Zdroj: Biochimica et Biophysica Acta, Vol. 1847, No 6-7 (2015) pp. 629-639
BBA-Biochimica et Biophysica Acta
BBA-Biochimica et Biophysica Acta, Elsevier, 2015, 1847 (6-7), pp.629-39. ⟨10.1016/j.bbabio.2015.04.002⟩
ISSN: 0005-2728
0006-3002
Popis: International audience; Deficit in oxygen and energetic substrates delivery is a key factor in islet loss during islet transplantation. Permeability transition pore (PTP) is a mitochondrial channel involved in cell death. We have studied the respective effects of oxygen and energy substrate deprivation on beta cell viability as well as the involvement of oxidative stress and PTP opening. Energy substrate deprivation for 1h followed by incubation in normal conditions led to a cyclosporin A (CsA)-sensitive-PTP-opening in INS-1 cells and human islets. Such a procedure dramatically decreased INS-1 cells viability except when transient removal of energy substrates was performed in anoxia, in the presence of antioxidant N-acetylcysteine (NAC) or when CsA or metformin inhibited PTP opening. Superoxide production increased during removal of energy substrates and increased again when normal energy substrates were restored. NAC, anoxia or metformin prevented the two phases of oxidative stress while CsA prevented the second one only. Hypoxia or anoxia alone did not induce oxidative stress, PTP opening or cell death. In conclusion, energy substrate deprivation leads to an oxidative stress followed by PTP opening, triggering beta cell death. Pharmacological prevention of PTP opening during islet transplantation may be a suitable option to improve islet survival and graft success.
Databáze: OpenAIRE
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