Differential effects of endo- and exopolyphosphatase expression on the induction of the mitochondrial permeability transition pore.

Inorganic polyphosphate (polyP) is a polymer that consists of a series of orthophosphates connected by high-energy phosphoanhydride bonds, like those found in ATP. In mammalian mitochondria, polyP has been linked to the activation of the mitochondrial permeability transition pore (mPTP). However, the details of this process are not completely understood.

Refractive Index Imaging Reveals That Elimination of the ATP Synthase C Subunit Does Not Prevent the Adenine Nucleotide Translocase-Dependent Mitochondrial Permeability Transition.

The mitochondrial permeability transition pore (mPTP) is a large, weakly selective pore that opens in the mitochondrial inner membrane in response to the pathological increase in matrix Ca concentration. mPTP activation has been implicated as a key factor contributing to stress-induced necrotic and apoptotic cell death. The molecular identity of the mPTP is not completely understood.

Investigation of Properties of the Mitochondrial Permeability Transition Pore Using Whole-Mitoplast Patch-Clamp Technique.

The mitochondrial permeability transition pore (mPTP) is a channel in the mitochondrial inner membrane that is activated by excessive calcium uptake. In this study, we used a whole-mitoplast patch-clamp approach to investigate the ionic currents associated with mPTP at the level of the whole single mitochondrion. The whole-mitoplast conductance was at the level of 5 to 7 nS, which is consistent with the presence of three to six single mPTP channels per mitochondrion.

Overexpression of , a Gene on Human Chromosome , Alters Cell Redox and Mitochondrial Function in Enamel Cells.

The regulator of calcineurin (RCAN1) has been implicated in the pathogenesis of Down syndrome (DS). Individuals with DS show dental abnormalities for unknown reasons, and RCAN1 levels have been found to be elevated in several tissues of DS patients. A previous microarray analysis comparing cells of the two main formative stages of dental enamel, secretory and maturation, showed a significant increase in RCAN1 expression in the latter.

Both ANT and ATPase are essential for mitochondrial permeability transition but not depolarization.

An increase in permeability of the mitochondrial inner membrane, mitochondrial permeability transition (PT), is the central event responsible for cell death and tissue damage in conditions such as stroke and heart attack. PT is caused by the cyclosporin A (CSA)-dependent calcium-induced pore, the permeability transition pore (PTP). The molecular details of PTP are incompletely understood.

Mitochondria modulate ameloblast Ca signaling.

The role of mitochondria in enamel, the most mineralized tissue in the body, is poorly defined. Enamel is formed by ameloblast cells in two main sequential stages known as secretory and maturation. Defining the physiological features of each stage is essential to understand mineralization.

Mitochondrial Dysfunction and Permeability Transition in Neonatal Brain and Lung Injuries.

This review discusses the potential mechanistic role of abnormally elevated mitochondrial proton leak and mitochondrial bioenergetic dysfunction in the pathogenesis of neonatal brain and lung injuries associated with premature birth. Providing supporting evidence, we hypothesized that mitochondrial dysfunction contributes to postnatal alveolar developmental arrest in bronchopulmonary dysplasia (BPD) and cerebral myelination failure in diffuse white matter injury (WMI). This review also analyzes data on mitochondrial dysfunction triggered by activation of mitochondrial permeability transition pore(s) (mPTP) during the evolution of perinatal hypoxic-ischemic encephalopathy.

Electrophysiological properties of the mitochondrial permeability transition pores: Channel diversity and disease implication.

The mitochondrial permeability transition pore (mPTP) is a channel that, when open, is responsible for a dramatic increase in the permeability of the mitochondrial inner membrane, a process known as the mitochondrial permeability transition (mPT). mPTP activation during Ca dyshomeostasis and oxidative stress disrupts normal mitochondrial function and induces cell death. mPTP opening has been implicated as a critical event in many diseases, including hypoxic injuries, neurodegeneration, and diabetes.

Cyclophilin D-dependent oligodendrocyte mitochondrial ion leak contributes to neonatal white matter injury.

Postnatal failure of oligodendrocyte maturation has been proposed as a cellular mechanism of diffuse white matter injury (WMI) in premature infants. However, the molecular mechanisms for oligodendrocyte maturational failure remain unclear. In neonatal mice and cultured differentiating oligodendrocytes, sublethal intermittent hypoxic (IH) stress activated cyclophilin D-dependent mitochondrial proton leak and uncoupled mitochondrial respiration, leading to transient bioenergetic stress.

The very low number of calcium-induced permeability transition pores in the single mitochondrion.

Mitochondrial permeability transition (PT) is a phenomenon of stress-induced increase in nonspecific permeability of the mitochondrial inner membrane that leads to disruption of oxidative phosphorylation and cell death. Quantitative measurement of the membrane permeability increase during PT is critically important for understanding the PT's impact on mitochondrial function. The elementary unit of PT is a PT pore (PTP), a single channel presumably formed by either ATP synthase or adenine nucleotide translocator (ANT).

Effects of GH/IGF on the Aging Mitochondria.

The mitochondria are key organelles regulating vital processes in the eukaryote cell. A decline in mitochondrial function is one of the hallmarks of aging. Growth hormone (GH) and the insulin-like growth factor-1 (IGF-1) are somatotropic hormones that regulate cellular homeostasis and play significant roles in cell differentiation, function, and survival.

Expression of Histone Deacetylases HDAC1 and HDAC2 and Their Role in Apoptosis in the Penumbra Induced by Photothrombotic Stroke.

In ischemic stroke, vascular occlusion rapidly induces tissue infarct. Over the ensuing hours, damage spreads to adjacent tissue and forms transition zone (penumbra), which is potentially salvageable. Epigenetic regulation of chromatin structure controls gene expression and protein synthesis.

Са- and NF-κB-dependent generation of NO in the photosensitized neurons and satellite glial cells.

Photodynamic therapy (PDT) is used for killing of malignant cells in tumors including brain cancer. It can also damage normal neurons and glial cells. Nitric oxide (NO) is known to control PDT-induced cell death.

Сlass II histone deacetylases in the post-stroke recovery period-expression, cellular, and subcellular localization-promising targets for neuroprotection.

Histone deacetylases (HDAC) inhibitors can protect nerve cells after a stroke, but it is unclear which HDAC isoform is involved in this effect. We studied cellular and intracellular rearrangement of class II HDACs at late periods after photothrombotic infarct (PTI) in the mouse sensorimotor cortex in the tissue surrounding the ischemia core and in the corresponding region of the contralateral hemisphere. We observed a decrease in HDAC4 in cortical neurons and an increase in its nuclear translocation.

ATP Synthase C-Subunit-Deficient Mitochondria Have a Small Cyclosporine A-Sensitive Channel, but Lack the Permeability Transition Pore.

Permeability transition (PT) is an increase in mitochondrial inner membrane permeability that can lead to a disruption of mitochondrial function and cell death. PT is responsible for tissue damage in stroke and myocardial infarction. It is caused by the opening of a large conductance (∼1.

Expression of Class I Histone Deacetylases in Ipsilateral and Contralateral Hemispheres after the Focal Photothrombotic Infarction in the Mouse Brain.

Histone acetylation and deacetylation are among the most important epigenetic processes that regulate gene expression. Nonselective inhibitors of histone deacetylases (HDAC) can protect brain cells during ischemia and stroke. However, which HDAC isoform is involved in this effect is unknown.

Reactive Oxygen Species Produced by a Photodynamic Effect Induced Calcium Signal in Neurons and Astrocytes.

Photodynamic therapy (PDT) leads to production of reactive oxygen species (ROS) and cell destruction due to oxidative stress. We used photodynamic effect of photosensitizer radachlorin to unravel the effect of photo-induced oxidative stress on the calcium signal and lipid peroxidation in primary culture of cortical neurons and astrocytes using live cell imaging. We have found that irradiation in presence of 200 nM of radachlorin induces calcium signal in primary neurons and astrocytes.

Photo-Induced Oxidative Stress Impairs Mitochondrial Metabolism in Neurons and Astrocytes.

Photodynamic therapy is selective destruction of cells stained with a photosensitizer upon irradiation with light at a specific wavelength in the presence of oxygen. Cell death upon photodynamic treatment is known to occur mainly due to free radical production and subsequent development of oxidative stress. During photodynamic therapy of brain tumors, healthy cells are also damaged; considering this, it is important to investigate the effect of the treatment on normal neurons and glia.

Involvement of MAPK, Akt/GSK-3β and AMPK/mTOR signaling pathways in protection of remote glial cells from axotomy-induced necrosis and apoptosis in the isolated crayfish stretch receptor.

Severe mechanical nerve injury such as axotomy can lead to neuron degeneration and death of surrounding glial cells. We showed that axotomy not only mechanically injures glial cells at the cutting location, but also induces necrosis or apoptosis of satellite glial cells remote from the transection site. Therefore, axon integrity is necessary for survival of surrounding glial cells.

On involvement of transcription factors nuclear factor kappa-light-chain-enhancer of activated B cells, activator protein-1 and signal transducer and activator of transcription-3 in photodynamic therapy-induced death of crayfish neurons and satellite glial cells.

Photodynamic therapy (PDT) is currently used in the treatment of brain tumors. However, not only malignant cells but also neighboring normal neurons and glial cells are damaged during PDT. In order to study the potential role of transcription factors-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), activator protein (AP-1), and signal transducer and activator of transcription-3 (STAT-3)-in photodynamic injury of normal neurons and glia, we photosensitized the isolated crayfish mechanoreceptor consisting of a single sensory neuron enveloped by glial cells.

The paired neuroglial and interglial membranes in the crayfish stretch receptor and their local disorganization.

The paired neuronal and glial membranes, or interglial membranes, which are separated by the narrow layer of the extracellular medium, are involved in intercellular communications. In the crayfish stretch receptor, the paired neuroglial membranes contain thin protein bridges (septate junctions) that maintain the intermembrane gap. In some places the paired membranes are locally disorganized.

Photodynamic effect of Radachlorin on nerve and glial cells.

Background: Radachlorin, a chlorine-derived photosensitizer, is used currently in photodynamic therapy (PDT) of skin cancer. In this work we studied Radachlorin-PDT effect on peripheral nerve and glial cells that are damaged along with tumor tissue.

Methods: We used simple model objects - a crayfish stretch receptor that consists of a single sensory neuron surrounded by glial cells and crayfish nerve cord consisting of nerve fibers and ganglia.