Amyloid beta (Abeta) plays a critical role in the pathophysiology of Alzheimer's disease. Increasing evidence indicates mitochondria as an important target of Abeta toxicity; however, the effects of Abeta toxicity on mitochondria have not yet been fully elucidated. Recent biochemical studies in vivo and in vitro implicate mitochondrial permeability transition pore (mPTP) formation involvement i...

When mammalian mitochondria are exposed to high calcium and phosphate, a massive swelling, uncoupling of respiration, and release of cytochrome c occur. These changes are mediated by opening of the mitochondrial permeability transition pore (MPTP). Activation of the MPTP in vivo in response to hypoxic and oxidative stress leads to necrotic and apoptotic cell death. Considering that embryos of t...

Parkinson's disease (PD) is characterized by a loss of ventral midbrain dopaminergic neurons, which can be modeled by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Inflammatory oxidants have emerged as key contributors to PD- and MPTP-related neurodegeneration. Here, we show that myeloperoxidase (MPO), a key oxidant-producing enzyme during inflammation, is upregulated in t...

AIMS The mitochondrial permeability transition pore (mPTP) plays a central role for tissue damage and cell death during ischaemia-reperfusion (I/R). We investigated the contribution of mitochondrial inorganic polyphosphate (polyP), a potent activator of Ca(2+)-induced mPTP opening, towards mPTP activation and cardiac cell death in I/R. METHODS AND RESULTS A significant increase in mitochondri...

In addition to their central role in ATP synthesis, mitochondria play a critical role in cell death. Oxidative stress accompanied by calcium overload, ATP depletion, and elevated phosphate levels induces mitochondrial permeability transition (MPT) with formation of nonspecific MPT pores (MPTP) in the inner mitochondrial membrane. Pore opening results in mitochondrial dysfunction with uncoupled ...

Studies have suggested that there are beneficial effects of exercise in patients with Parkinson's disease, but the underlying molecular mechanisms responsible for these effects are poorly understood. Studies in rodent models provide a means to examine the effects of exercise on dopaminergic neurotransmission. Using intensive treadmill exercise, we determined changes in striatal dopamine in the ...

Exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes loss of dopaminergic neurons in humans, primates and mice. Exposure of sagittal slices of mouse brain to MPTP (100 pM) caused inhibition of mitochondrial NADH-dehydrogenase activity. Leakage of lactate dehydrogenase from the slice into the medium was observed following incubation of slices with 1 nM MPTP. Neurotoxicity induc...

Parkinson’s disease (PD) is a neurodegenerative characterized by the progressive degeneration of dopaminergic neurons in substantia nigra. Oxidative stress-induced neuronal death has been identified as one major causes nigrostriatal PD. The fruit Actinidia arguta (A. arguta), known sarunashi Japan, reported to show beneficial health effects such antioxidant, anti-inflammatory, anti-mutagenic, a...

BACKGROUND The inhalation anesthetic isoflurane has been shown to open the mitochondrial permeability transition pore (mPTP) and induce caspase activation and apoptosis, which may lead to learning and memory impairment. Cyclosporine A, a blocker of mPTP opening might attenuate the isoflurane-induced mPTP opening, lessening its ripple effects. Magnesium and anesthetic propofol are also mPTP bloc...

OBJECTIVE Coated-platelets are a subset of cells observed during costimulation of platelets with collagen and thrombin. Important characteristics of coated-platelets include retention of multiple alpha-granule proteins and expression of phosphatidylserine on the cell surface. The mitochondrial permeability transition pore (MPTP) is a key step in apoptosis and is suggested to be involved in some...