Energy-dependent Process Research Articles

Myocardial hypertrophy reduces transmural variation in mitochondrial function.

Myocardial hypertrophy reduces transmural variation in mitochondrial function.

Dioctadecyldimethylammonium:Monoolein Nanocarriers for Efficient in Vitro Gene Silencing

This study describes a novel liposomal formulation for siRNA delivery, based on the mixture of the neutral lipid monoolein (MO) and cationic lipids of the dioctadecyldimethylammonium (DODA) family. The cationic lipids dioctadecyldimethylammonium bromide (DODAB) and chloride (DODAC) were compared in order to identify which one will most efficiently induce gene silencing. MO has a fluidizing effect on DODAC and DODAB liposomes, although it was more homogeneously distributed in DODAC bilayers. All MO-based liposomal formulations were able to efficiently encapsulate siRNA. Stable lipoplexes of small size (100-160 nm) with a positive surface charge (>+45 mV) were formed. A more uniform MO incorporation in DODAC:MO may explain an increase of the fusogenic potential of these liposomes. The siRNA-lipoplexes were readily internalized by human nonsmall cell lung carcinoma (H1299) cells, in an energy dependent process. DODAB:MO nanocarriers showed a higher internalization efficiency in comparison to DODAC:MO lipoplexes, and were also more efficient in promoting gene silencing. MO had a similar gene silencing ability as the commonly used helper lipid 1,2-dioleyl-3-phosphatidylethanolamine (DOPE), but with much lower cytotoxicity. Taking in consideration all the results presented, DODAB:MO liposomes are the most promising tested formulation for systemic siRNA delivery.

Examining egg laying circadian rhythm phenotypes in a glycolytic mutant fly model (883.3)

Triosephosphate Isomerase (TPI) is a glycolytic enzyme. Mutations in this enzyme are associated with a neurodegenerative disorder called TPI Deficiency in humans. In addition to neurological health other cellular processes may be affected by alterations in sugar metabolism. We developed an experiment to assess if flies with a mutant TPI allele called “sugarkill” exhibit reduced egg production or alterations in the circadian rhythm of egg production. Egg production is a highly energy dependent process and therefore alterations in energy production may decrease the ability of the animals to produce eggs. In addition, flies exhibit circadian rhythm phenotypes, of which, include egg laying primarily in the morning. If neurological function is altered, the circadian rhythm for the flies may be altered as well. For this experiment, two different genotypes of Drosophila melanogaster were utilized: flies were either homozygous for the wildtype TPI allele or the mutant TPIsugarkill allele. With each genotype matings were set up with 4 virgin females to every 12 males and then the number of eggs was counted every 4 hours during 12 hour cycles from 7am‐7pm in an incubator set at 25C. Results indicate that while the average clutch size is not different during a 24 hour period the circadian rhythm pattern for egg laying and eclosion is altered in TPIsugarkill flies.

Reduced Warburg Effect in Cancer Cells Undergoing Autophagy: Steady- State 1H-MRS and Real-Time Hyperpolarized 13C-MRS Studies

Autophagy is a highly regulated, energy dependent cellular process where proteins, organelles and cytoplasm are sequestered in autophagosomes and digested to sustain cellular homeostasis. We hypothesized that during autophagy induced in cancer cells by i) starvation through serum and amino acid deprivation or ii) treatment with PI-103, a class I PI3K/mTOR inhibitor, glycolytic metabolism would be affected, reducing flux to lactate, and that this effect may be reversible. We probed metabolism during autophagy in colorectal HT29 and HCT116 Bax knock-out cells using hyperpolarized 13C-magnetic resonance spectroscopy (MRS) and steady-state 1H-MRS. 24 hr PI103-treatment or starvation caused significant reduction in the apparent forward rate constant (kPL) for pyruvate to lactate exchange compared with controls in HT29 (100 μM PI-103: 82%, p = 0.05) and HCT116 Bax-ko cells (10 μM PI-103: 53%, p = 0.05; 20 μM PI-103: 42%, p<0.0001; starvation: 52%, p<0.001), associated with reduced lactate excretion and intracellular lactate in all cases, and unchanged lactate dehydrogenase (LDH) activity and increased NAD+/NADH ratio following PI103 treatment or decreased LDH activity and unchanged NAD+/NADH ratio following starvation. After 48 hr recovery from PI103 treatment, kPL remained below control levels in HT29 cells (74%, p = 0.02), and increased above treated values, but remained below 24 hr vehicle-treated control levels in HCT116 Bax-ko cells (65%, p = 0.004) both were accompanied by sustained reduction in lactate excretion, recovery of NAD+/NADH ratio and intracellular lactate. Following recovery from starvation, kPL was significantly higher than 24 hr vehicle-treated controls (140%, p = 0.05), associated with increased LDH activity and total cellular NAD(H). Changes in kPL and cellular and excreted lactate provided measureable indicators of the major metabolic processes accompanying starvation- and drug-induced autophagy. The changes are reversible, returning towards and exceeding control values on cellular recovery, which potentially identifies resistance. kPL (hyperpolarized 13C-MRS) and lactate (1H-MRS) provide useful biomarkers for the autophagic process, enabling non-invasive monitoring of the Warburg effect.

Mechanisms of epileptogenesis in pediatric epileptic syndromes: Rasmussen encephalitis, infantile spasms, and febrile infection-related epilepsy syndrome (FIRES).

The mechanisms of epileptogenesis in pediatric epileptic syndromes are diverse, and may involve disturbances of neurodevelopmental trajectories, synaptic homeostasis, and cortical connectivity, which may occur during brain development, early infancy, or childhood. Although genetic or structural/metabolic factors are frequently associated with age-specific epileptic syndromes, such as infantile spasms and West syndrome, other syndromes may be determined by the effect of immunopathogenic mechanisms or energy-dependent processes in response to environmental challenges, such as infections or fever in normally-developed children during early or late childhood. Immune-mediated mechanisms have been suggested in selected pediatric epileptic syndromes in which acute and rapidly progressive encephalopathies preceded by fever and/or infections, such as febrile infection-related epilepsy syndrome, or in chronic progressive encephalopathies, such as Rasmussen encephalitis. A definite involvement of adaptive and innate immune mechanisms driven by cytotoxic CD8(+) T lymphocytes and neuroglial responses has been demonstrated in Rasmussen encephalitis, although the triggering factor of these responses remains unknown. Although the beneficial response to steroids and adrenocorticotropic hormone of infantile spasms, or preceding fever or infection in FIRES, may support a potential role of neuroinflammation as pathogenic factor, no definite demonstration of such involvement has been achieved, and genetic or metabolic factors are suspected. A major challenge for the future is discovering pathogenic mechanisms and etiological factors that facilitate the introduction of novel targets for drug intervention aimed at interfering with the disease mechanisms, therefore providing putative disease-modifying treatments in these pediatric epileptic syndromes.

Cellular internalization of doxorubicin loaded star-shaped micelles with hydrophilic zwitterionic sulfobetaine segments

Four arm star-shaped poly(ε-caprolactone)-b-poly((N,N-diethylaminoethyl methacrylate)-r-(N-(3-sulfopropyl)-N-methacryloxyethy-N,N-diethylammoniumbetaine)) (4sPCLDEAS) micelles were loaded with anticancer drug doxorubicin to track their endocytosis in Hela cancer cell line. The effects of mean diameters and surface charges of the drug loaded micelles on the cellular uptake were studied in details. The results demonstrated that the internalization of micelles was both time and energy dependent process. Endocytic pathways including clathrin-mediated endocytosis, caveolae-mediated endocytosis and macropinocytosis were all involved in the internalization; caveolae-mediated endocytosis was the main pathway for the internalization of 4sPCLDEAS micelles. The assays for cell apoptosis and growth inhibition of tumor spheroids identified that these doxorubicin loaded micelles could induce cell apoptosis and inhibit tumor spheroids growth efficiently, which was even equal to free DOX·HCl. This study provided a rational design strategy for fabricating diverse micellar drug delivery systems with high anticancer efficiency.

Lanthanide-doped nanoparticles for specific recognition of toll-like receptor (TLR) in human neutrophils

KYF4:Yb,Er nanoparticles were fabricated and functionalized with streptavidin for the recognition of toll-like receptors (TLRs) on human neutrophil through biotinylated lipopolysaccharide (biotin–LPS). X-Ray diffraction, Infrared spectroscopy, Transmission Electron Microscopy and Agarose Gel Electrophoresis were used to characterize the as-prepared and functionalized nanoparticles. Confocal Scanning Laser Microscopy was applied to study the TLR specific recognition using KYF4:Yb,Er and the uptake of the nanoparticles functionalized with BSA/Dextran–streptavidin in the presence of biotin–LPS by human neutrophils under normal (37 °C) and cell stressing conditions (4 °C). Confocal microscopy studies showed that the uptake of the functionalized KYF4:Yb,Er nanoparticles occurs faster and with a higher rate at 37 °C compared to the uptake at 4 °C, indicating that the uptake mechanism is an energy dependent process. Research reported in this work provides relevant guidance for the development of lanthanide doped KYF4:Yb,Er nanoparticles as specific intracellular probes, allowing control of the nanoparticle–cell interactions by tuning the surface properties. Furthermore, our results would pave the way to the use of lanthanide-doped materials for imaging cellular processes such as uptake of nanoparticles and recognition of receptors involved in immune responses.

The interaction between nanoparticles and biological barriers

Biological barriers are truly one of the most perfect biological machines to have been studied. They perform a primary function of preventing undesired access to sensitive organs, while allowing for limited and selected passage across. They thereby manage access of a variety of molecules and assemblies with an efficiency and fidelity that no man-made engineered filter or barrier can even approach. Without such a barrier, for example the lungs, our bloodstream and subsequently all our organs would be exposed to a multitude of dangerous inhalation scenarios. Most delicate of all, the brain would be unable to function in the face of a variety of infections and other challenges. The basis of the success of the biological barrier is that the primary component of the barrier is composed of an array of tightly joined cells backed up by an array of other cells involved in clearance, immunity and other processes. Thus, while some very small molecular weight molecules can diffuse or passively partition across the barriers, most molecules and other undesirable larger assemblies are excluded, or removed, by active biological processes. Those larger molecules that pass the barrier must traffic across using active energy dependent biological processes, during which they are exposed to many intracellular checks and analyses. Naturally, the very success of biological barriers in excluding passage can present very significant (arguably, currently often insuperable) challenges for the delivery of therapies across the barriers. For example, many of the more intractable human brain-related diseases ranging from neurodegeneration, persistent drug cocktail resistant viral infection (HIV for example), and glioblastomas, are exacerbated by the difficulty of gaining therapeutic access to the brain. Great inconvenience and expense is added to numerous other therapeutic scenarios in which biological barriers have to be crossed before drugs can act. Nanomedicine, were it to allow us to address these challenges, would by this achievement alone change the face of medicine, and justify the endeavour. However, a survey of recent efforts suggests that nanoparticles, while they offer important developmental directions, do not automatically, and, naively applied, will not lead to immediate simplistic solutions, based on size alone. Certainly nanoparticles are exceptional in that, due to their

Leptin Metabolically Licenses T Cells for Activation To Link Nutrition and Immunity

Immune responses are highly energy-dependent processes. Activated T cells increase glucose uptake and aerobic glycolysis to survive and function. Malnutrition and starvation limit nutrients and are associated with immune deficiency and increased susceptibility to infection. Although it is clear that immunity is suppressed in times of nutrient stress, mechanisms that link systemic nutrition to T cell function are poorly understood. We show in this study that fasting leads to persistent defects in T cell activation and metabolism, as T cells from fasted animals had low glucose uptake and decreased ability to produce inflammatory cytokines, even when stimulated in nutrient-rich media. To explore the mechanism of this long-lasting T cell metabolic defect, we examined leptin, an adipokine reduced in fasting that regulates systemic metabolism and promotes effector T cell function. We show that leptin is essential for activated T cells to upregulate glucose uptake and metabolism. This effect was cell intrinsic and specific to activated effector T cells, as naive T cells and regulatory T cells did not require leptin for metabolic regulation. Importantly, either leptin addition to cultured T cells from fasted animals or leptin injections to fasting animals was sufficient to rescue both T cell metabolic and functional defects. Leptin-mediated metabolic regulation was critical, as transgenic expression of the glucose transporter Glut1 rescued cytokine production of T cells from fasted mice. Together, these data demonstrate that induction of T cell metabolism upon activation is dependent on systemic nutritional status, and leptin links adipocytes to metabolically license activated T cells in states of nutritional sufficiency.

Micromechanics of quartz sand breakage in a fractal context

From a Quaternary science perspective, sand-sized quartz as well as silt-sized quartz is often acknowledged as final products of glacial abrasion through different evolution mechanisms. This view challenges the existence of any universal comminution process, which may relate the formation of detrital quartz sand and silt. The contribution of grain size, energy input, and crystalline integrity in the scale of quartz crushability has long been the matter of much debate. The present empirical work examines the micromechanics of sand-to-silt size reduction in the quartz material. A series of grinding experiments was performed on Leighton Buzzard Lower Greensand using a high-energy agate disc mill. Analogous conditions to glacial abrasion are provided due to the combined abrasion between grains' asperity tips, and also between grains and rotating smooth tungsten carbide pestle. Simulation of discontinuous grain breakage allowed the examination of grains' crystalline defects. To enable an objective assessment of micromechanics of size reduction, measurements of particle and mode size distribution, fractal indexes and micro-morphological signatures were made. The crushing approach was probed through varied grinding times at a constant energy input, as well as varied energy inputs at constant grinding time. Breakage pathway was inspected via laser diffraction spectroscopy and transmission light microscopy. Results suggested that the grain breakdown is not necessarily an energy-dependent process. Non-crystallographically pure (amorphous) quartz sand and silt are inherently breakable materials through a fractal breakdown process. Results also revealed that the internal defects in quartz are independent from size and energy input.

Genome-wide probing of RNA structure reveals active unfolding of mRNA structures in vivo

RNA plays a dual role as an informational molecule and a direct effector of biological tasks. The latter function is enabled by RNA’s ability to adopt complex secondary and tertiary folds and thus has motivated extensive computational1–2 and experimental3–8 efforts for determining RNA structures. Existing approaches for evaluating RNA structure have been largely limited to in vitro systems, yet the thermodynamic forces which drive RNA folding in vitro may not be sufficient to predict stable RNA structures in vivo5. Indeed, the presence of RNA binding proteins and ATP-dependent helicases can influence which structures are present inside cells. Here we present an approach for globally monitoring RNA structure in native conditions in vivo with single nucleotide precision. This method is based on in vivo modification with dimethyl sulfate (DMS), which reacts with unpaired adenine and cytosine residues9, followed by deep sequencing to monitor modifications. Our data from yeast and mammalian cells are in excellent agreement with known mRNA structures and with the high-resolution crystal structure of the Saccharomyces cerevisiae ribosome10. Comparison between in vivo and in vitro data reveals that in rapidly dividing cells there are vastly fewer structured mRNA regions in vivo than in vitro. Even thermostable RNA structures are often denatured in cells, highlighting the importance of cellular processes in regulating RNA structure. Indeed, analysis of mRNA structure under ATP-depleted conditions in yeast reveals that energy-dependent processes strongly contribute to the predominantly unfolded state of mRNAs inside cells. Our studies broadly enable the functional analysis of physiological RNA structures and reveal that, in contrast to the Anfinsen view of protein folding, thermodynamics play an incomplete role in determining mRNA structure in vivo.

Trans-membrane transport of n-octadecane by Pseudomonas sp. DG17

The trans-membrane transport of hydrocarbons is an important and complex aspect of the process of biodegradation of hydrocarbons by microorganisms. The mechanism of transport of (14)C n-octadecane by Pseudomonas sp. DG17, an alkane-degrading bacterium, was studied by the addition of ATP inhibitors and different substrate concentrations. When the concentration of n-octadecane was higher than 4.54 μmol/L, the transport of (14)C n-octadecane was driven by a facilitated passive mechanism following the intra/extra substrate concentration gradient. However, when the cells were grown with a low concentration of the substrate, the cellular accumulation of n-octadecane, an energy-dependent process, was dramatically decreased by the presence of ATP inhibitors, and n-octadecane accumulation continually increased against its concentration gradient. Furthermore, the presence of non-labeled alkanes blocked (14)C n-octadecane transport only in the induced cells, and the trans-membrane transport of n-octadecane was specific with an apparent dissociation constant K t of 11.27 μmol/L and V max of 0.96 μmol/min/mg protein. The results indicated that the trans-membrane transport of n-octadecane by Pseudomonas sp. DG17 was related to the substrate concentration and ATP.

Identification of glucose transporters in Aspergillus nidulans.

To characterize the mechanisms involved in glucose transport, in the filamentous fungus Aspergillus nidulans, we have identified four glucose transporter encoding genes hxtB-E. We evaluated the ability of hxtB-E to functionally complement the Saccharomyces cerevisiae EBY.VW4000 strain that is unable to grow on glucose, fructose, mannose or galactose as single carbon source. In S. cerevisiae HxtB-E were targeted to the plasma membrane. The expression of HxtB, HxtC and HxtE was able to restore growth on glucose, fructose, mannose or galactose, indicating that these transporters accept multiple sugars as a substrate through an energy dependent process. A tenfold excess of unlabeled maltose, galactose, fructose, and mannose were able to inhibit glucose uptake to different levels (50 to 80 %) in these s. cerevisiae complemented strains. Moreover, experiments with cyanide-m-chlorophenylhydrazone (CCCP), strongly suggest that hxtB, -C, and –E mediate glucose transport via active proton symport. The A. nidulans ΔhxtB, ΔhxtC or ΔhxtE null mutants showed ~2.5-fold reduction in the affinity for glucose, while ΔhxtB and -C also showed a 2-fold reduction in the capacity for glucose uptake. The ΔhxtD mutant had a 7.8-fold reduction in affinity, but a 3-fold increase in the capacity for glucose uptake. However, only the ΔhxtB mutant strain showed a detectable decreased rate of glucose consumption at low concentrations and an increased resistance to 2-deoxyglucose.

Low temperature inhibits pollen tube growth by disruption of both tip-localized reactive oxygen species and endocytosis in Pyrus bretschneideri Rehd.

Low temperature (LT) negatively affects fertilization processes of flowering plants. Pollen tube growth is generally inhibited under LT stress; however, the mechanism(s) underlying this inhibition remain(s) largely unknown. Pollen tubes are tip-growing and the presence of tip-localized reactive oxygen species (ROS) is necessary for cellular functioning. Disruption of tip-localized ROS was observed in pear pollen tubes in vitro under low temperature of 4 °C (LT4). Diphenylene iodonium chloride, an NADPH oxidase (NOX) inhibitor, suppressed hydrogen peroxide formation in the cell walls of the subapical region in pear pollen tubes. Under LT4 stress, ROS disruption in pear pollen tubes mainly resulted from decreased NOX activity in the plasma membrane, indicating that NOX was the main source of ROS in this process. Moreover, LT4 remarkably decreased mitochondrial oxygen consumption and intracellular ATP production. The endocytosis, an energy-dependent process, disruption in pear pollen tubes under LT4 may be mediated by mitochondrial metabolic dysfunctions. Our data showed ROS and endocytosis events in pear pollen tubes responding to LT4 stress.

Identification and Molecular Characterization of YsaL (Ye3555): A Novel Negative Regulator of YsaN ATPase in Type Three Secretion System of Enteropathogenic Bacteria Yersinia enterocolitica

Type Three Secretion (T3S) ATPases are involved in delivery of virulent factors from bacteria to their hosts (through injectisome) in an energy (ATP) dependent manner during pathogenesis. The activities of these ATPases are tightly controlled by their specific regulators. In Yersinia enterocolitica, YsaN was predicted as a putative ATPase of the Ysa-Ysp Type Three Secretion System (T3SS) based on sequence similarity with other T3S ATPases. However detailed study and characterization of YsaN and its regulation remains largely obscure. Here, in this study, we have successfully cloned, over-expressed, purified and characterized the molecular properties of YsaN from Yersinia enterocolitica. YsaN acts as a Mg2+ dependent ATPase and exists in solution as higher order oligomer (dodecamer). The ATPase activity of oligomeric YsaN is several fold higher than the monomeric form. Furthermore, by employing in silico studies we have identified the existence of a negative regulator of YsaN- a hypothetical protein YE3555 (termed ‘YsaL’). To verify the functionality of YsaL, we have evaluated the biochemical and biophysical properties of YsaL. Purified YsaL is dimeric in solution and strongly associates with YsaN to form a stable heterotrimeric YsaL-YsaN complex (stoichiometry- 2∶1). The N terminal 6–20 residues of YsaN are invariably required for stable YsaL-YsaN complex formation. YsaL inhibited the ATPase activity of YsaN with a maximum inhibition at the molar ratio 2∶1 (YsaL: YsaN). In short, our studies provide an insight into the presence of YsaN ATPase in Yersinia enterocolitica and its regulator YsaL. Our studies also correlate the functionality of one of the existing protein interaction networks that possibly is indispensable for the energy dependent process of Ysa-Ysp T3SS in pathogenic Yersinia enterocolitica.

Transferrin Receptor Mediated Brain Uptake During Ischemia and Reperfusion

Drug delivery by transferrin receptor-mediated transport at the blood-brain barrier has shown beneficial effects in animal models of stroke, but it is unclear whether receptor mediated uptake remains functional in the ischemic tissue. The present study addressed that question in a mouse model of brain focal ischemia, permanent or transient middle cerebral artery occlusion (MCAO). Brain accumulation of 125I-labeled 8D3, a mouse-specific transferrin receptor antibody, or of the isotype control UPC-10 used as vascular marker, was measured autoradiographically by phosphorimaging in the core ischemic region on cryostat brain sections up to 24h after ischemia or reperfusion. Cerebral blood flow was quantitatively determined in the same animals after administration of 99mTc-ECD (Neurolite). Apparent volume of distribution obtained with UPC-10 indicated no significant nonspecific leakage of the blood-brain barrier at any time point. Although brain uptake of 8D3 gradually declined compared to healthy tissue under MCAO, VD remained significantly higher than VD of UPC-10 up to 5h. In transient MCAO the brain uptake recovered to levels as in healthy tissue immediately after reperfusion. Transferrin receptor-mediated brain uptake, which is an energy dependent vesicular transport process, is sensitive to reduction in blood supply but remains partially functional for several hours after onset of ischemia. The uptake shows complete recovery after reperfusion. These results support the use of transferrin receptor-mediated brain drug delivery in the early phase of ischemia and in the phase when blood flow is restored. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Cellular Uptake and Transport of Zein Nanoparticles: Effects of Sodium Caseinate

Cellular evaluation of zein nanoparticles has not been studied systematically due to their poor redispersibility. Caseinate (CAS)-stabilized zein nanoparticles have been recently developed with better redispersibility in salt solutions. In this study, zein-CAS nanoparticles were prepared with different zein/CAS mass ratios. The prepared nanoparticles demonstrated good stabilities to maintain particle size (120-140 nm) in cell culture medium and HBSS buffer at 37 °C. The nanoparticles showed no cytotoxicity for Caco-2 cells for 72 h. CAS not only significantly enhanced cell uptake of zein nanoparticles in a concentration- and time-dependent manner but also remarkably improved epithelial transport through Caco-2 cell monolayer. The cell uptake of zein-CAS nanoparticles indicated an energy-dependent endocytosis process as evidenced by cell uptake under blocking conditions, that is, 4 °C, sodium azide, and colchicine. Fluorescent microscopy clearly showed the internalization of zein-CAS nanoparticles. This study may shed some light on the cellular evaluations of hydrophobic protein nanoparticles.

Evaluation of the protection exerted by Pisum sativum Ferredoxin-NADP(H) Reductase against injury induced by hypothermia on Cos-7 cells

Hypothermia is employed as a method to diminish metabolism rates and preserve tissues and cells. However, low temperatures constitute a stress that produces biochemical changes whose extension depends on the duration and degree of cold exposure and is manifested when physiological temperature is restored. For many cellular types, cold induces an oxidative stress that is dependent on the elevation of intracellular iron, damages macromolecules, and is prevented by the addition of iron chelators. Pisum sativum Ferredoxin-NADP(H) Reductase (FNR) has been implicated in protection from injury mediated by intracellular iron increase and successfully used to reduce oxidative damage on bacterial, plant and mammalian systems. In this work, FNR was expressed in Cos-7 cells; then, they were submitted to cold incubation and iron overload to ascertain whether this enzyme was capable of diminishing the harm produced by these challenges. Contrary to expected, FNR was not protective and even exacerbated the damage under certain circumstances. It was also found that the injury induced by hypothermia in Cos-7 cells presented both iron-dependent and iron-independent components of damage when cells were actively dividing but only iron-independent component when cells were in an arrested state. This is in agreement with previous findings which showed that iron-dependent damage is also an energy-dependent process.

Introduction: the unfolded protein response’s role in disease pathophysiology

Introduction: the unfolded protein response’s role in disease pathophysiology

Влияние потенциалзависимого транспорта калия на мембранный потенциал митохондрий мозга крыс

The effect of potential-dependent potassium uptake on the transmembrane potential difference (DeltaPsi(m)) in rat brain mitochondria has been studied. It was shown that in potassium concentration range of 0-120 mM the potential-dependent K(+)-uptake into matrix leads to the increase in respiration rate and mitochondrial depolarization. ATP-dependent potassium channel (K+(ATP)-channel) blockers, glibenclamide and 5-hydroxydecanoate, block approximately 35% of potential-dependent potassium uptake in the brain mitochondria. It was shown that K+(ATP)-channel blockage results in membrane repolarization by approximately 20% of control, which is consistent with experimental dependence of DeltaPsi(m) on the rate of potential-dependent potassium uptake. Obtained experimental data give the evidence that functional activity of K+(ATP)-channel is physiologically important in the regulation of membrane potential and energy-dependent processes in brain mitochondria.