Postconditioning has recently been described as a powerful cardioprotection that prevents lethal reperfusion injury. Growing evidence suggests that mitochondrial permeability transition may be a key event in postconditioning. This proposition arises from the complementary observations that: (1) conditions for the mitochondrial permeability transition pore (mPTP) opening are built up during earl...

In recent years, the concept of the mitochondrial permeability transition pore (mPTP) has attracted considerable attention from researchers in the field of pathophysiology, focusing on mitochondrial function as a potential therapeutic target. Indeed, given that the mPTP is considered to be the main and final effector of cell death in various disorders, numerous and progressive efforts have been...

chloroacetaldehyde (caa) is a chlorination by-product in finished drinking water and a toxic metabolite of a wide variety of industrial chemicals (e.g. vinyl chloride) and chemotherapeutic agents (e.g. cyclophosphamide and ifosfamide). in this research, the cytotoxic mechanisms of caa in freshly isolated rat hepatocytes were investigated.caa cytotoxicity was associated with reactive oxygen spec...

Mitochondria from transgenic mice, expressing enzymatically active mitochondrial creatine kinase in liver, were analyzed for opening of the permeability transition pore in the absence and presence of creatine kinase substrates but with no external adenine nucleotides added. In mitochondria from these transgenic mice, cyclosporin A-inhibited pore opening was delayed by creatine or cyclocreatine ...

Mitochondrial permeability transition pore (MPTP) is a transient structure formed in the inner mitochondrial membrane (IMM) upon oxidative challenge of the organelle. The transition is a Ca 2+ -dependent increase of permeability of IMM leading to loss of transmembrane potential (∆ψm), mitochondrial swelling and, finally, rupture of outer mitochondrial membrane leading to release of factors caus...

BACKGROUND Loss of function mutations in the DJ-1 gene have been linked to recessively inherited forms of Parkinsonism. Mitochondrial dysfunction and increased oxidative stress are thought to be key events in the pathogenesis of Parkinson's disease. Although it has been reported that DJ-1 serves as scavenger for reactive oxidative species (ROS) by oxidation on its cysteine residues, how loss of...

The mitochondrial permeability transition is a widely studied, but poorly understood, phenomenon in mitochondrial bioenergetics. It has been recognised that this phenomenon is related to the opening of a protein pore in the inner mitochondrial membrane, and that opening of this pore is the cause of some forms of mitochondrial dysfunction. In this work, we propose that carvedilol, a multi-role c...

Cyclosporin A induces closure of the mitochondrial permeability transition pore. We aimed to investigate whether this closure results in concomitant increases in mitochondrial membrane potential (DeltaPsim) and the production of reactive oxygen species. Fluorescent probes were used to assess DeltaPsim (JC-1, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-benzimidazolyl-carbocyanine iodide), reactiv...

Antamanide is a cyclic decapeptide derived from the fungus Amanita phalloides. Here we show that antamanide inhibits the mitochondrial permeability transition pore, a central effector of cell death induction, by targeting the pore regulator cyclophilin D. Indeed, (i) permeability transition pore inhibition by antamanide is not additive with the cyclophilin D-binding drug cyclosporin A, (ii) the...

in this research, we investigated the cytotoxic mechanisms of one of the widely used pharmaceuticals that are regularly associated with the adverse effects on the liver, sometimes leading to acute liver failure, diclofenac. diclofenac liver cytotoxicity was associated with reactive oxygen species (ros) formation and lipid peroxidation which were inhibited by antioxidants and ros scavengers, fer...