Leptin Modifies the Rat Heart Performance Associated with Mitochondrial Dysfunction Independently of Its Prohypertrophic Effects

Background. Functional receptors for leptin were described on the surface of cardiomyocytes, and there was a prohypertrophic effect with high concentrations of the cytokine. Therefore, leptin could be a link between obesity and the prevalence of cardiovascular diseases. On the other hand, a deleterious effect of leptin on mitochondrial performance was described, which was also associated with the evolution of cardiac hypertrophy to heart failure. The goal of our study was to analyze the effect of the exposure of rat hearts to a high concentration of leptin on cardiac and mitochondrial function. Methods. Rat hearts were perfused continuously with or without 3.1 nM leptin for 1, 2, 3, or 4 hours. Homogenates and mitochondria were prepared by centrifugation and analyzed for cardiac actin, STAT3, and pSTAT3 by Western blotting, as well as for mitochondrial oxidative phosphorylation, membrane potential, swelling, calcium transport, and content of oxidized lipids. Results. In our results, leptin induced an increased rate-pressure product as a result of increased heart rate and contraction force, as well oxidative stress. In addition, mitochondrial dysfunction expressed as a loss of membrane potential, decreased ability for calcium transport and retention, faster swelling, and less respiratory control was observed. Conclusions. Our results support the role of leptin as a deleterious factor for cardiac function and indicates that mitochondrial dysfunction could be a trigger for cardiac hypertrophy and failure.

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Freezing survival by isolated Malpighian tubules of the New Zealand alpine weta Hemideina maori.

Journal of Experimental Biology ◽

10.1242/jeb.201.2.227 ◽

1998 ◽

Vol 201 (2) ◽

pp. 227-236 ◽

Cited By ~ 3

Author(s):

D S Neufeld ◽

L P Leader

Keyword(s):

New Zealand ◽

Membrane Potential ◽

Basolateral Membrane ◽

Fluid Secretion ◽

Malpighian Tubules ◽

High Concentration ◽

Freeze Thaw ◽

Thaw Cycle ◽

Freeze Thaw Cycle ◽

High Concentrations

The ability of isolated Malpighian tubules from a freeze-tolerant insect, the New Zealand alpine weta (Hemideina maori), to withstand freezing was assessed by measuring post-freeze membrane potentials and rates of fluid secretion. The hemolymph of cold-acclimated Hemideina maori was found to contain relatively high concentrations of the cryoprotectants trehalose (>300 mmol l-1) and proline (41 mmol l-1). Survival of isolated Malpighian tubules was correspondingly high when a high concentration of trehalose was present in the bathing saline. Tubules allowed to recover for 20 min from a 1 h freeze to -5 degrees C in saline containing 400 mmol l-1 trehalose had a basolateral membrane potential of -53 mV compared with a potential of -63 mV in tubules not exposed to a freeze/thaw cycle. Fluid secretion in tubules that had experienced a freeze/thaw cycle in saline containing 400 mmol l-1 trehalose was 9.9+/-2.6 nl h-1 compared with 18.7+/-5.0 nl h-1 (means +/- s.e.m., N=18) in tubules that had not been frozen. Tubules frozen in saline containing a lower concentration of trehalose (200 mmol l-1) or in glucose (400 mmol l-1) showed a similar ability to survive freezing to -5 degrees C. In contrast, freezing for 1 h at -5 degrees C in saline containing 400 mmol l-1 sucrose produced a 57 % decrease in membrane potential and an 88 % decrease in secretion rate. Tubules held in saline lacking high concentrations of sugars showed no survival after freezing to -5 degrees C for 1 h. When frozen to -15 degrees C, tubules appeared to survive best in saline with the highest trehalose concentration (400 mmol l-1). Freezing damage was not simply the result of exposure to cold, since tubules chilled (unfrozen) to -5 degrees C for 1 h were not compromised even when the bathing saline lacked a high sugar concentration. Exposure of tubules to a combination of low temperature and high osmolality mimicked damage caused by actual freezing: the membrane potential showed a 60 % recovery when the test was performed in saline containing trehalose, but showed no recovery in saline containing sucrose.

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Lipid-II Independent Antimicrobial Mechanism of Nisin Depends On Its Crowding And Degree Of Oligomerization

Scientific Reports ◽

10.1038/srep37908 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 34

Author(s):

Ashutosh Prince ◽

Padmani Sandhu ◽

Pankaj Ror ◽

Eva Dash ◽

Shingarika Sharma ◽

...

Keyword(s):

Escherichia Coli ◽

Bacillus Subtilis ◽

Membrane Potential ◽

Cell Viability ◽

Lag Phase ◽

High Concentration ◽

Lipid Ii ◽

C Terminus ◽

High Concentrations ◽

Dynamics Simulations

Abstract Nisin inhibits bacterial growth by generating pores in cell membrane and interrupting cell-wall biosynthesis through specific lipid II interaction. However, the role of the hinge region and C-terminus residues of the peptide in antibacterial action of nisin is largely unknown. Here, using molecular dynamics simulations and experimental approach, we report that at high concentration regimes of nisin, interaction with phospholipids may equally deform the bacterial cell membranes even under significantly varying amounts of lipid-II. Membrane thinning, destabilization and decrease in lipid density depend on the degree of oligomerization of nisin. Growth kinetics of Bacillus subtilis and Escherichia coli interestingly show recovery by extended lag phase under low concentrations of nisin treatment while high concentrations of nisin caused decrease in cell viability as recorded by striking reduction in membrane potential and surface area. The significant changes in the dipole potential and fluorescence anisotropy were observed in negatively charged membranes in the absence of lipid-II with increasing concentration of nisin. The identical correlation of cell viability, membrane potential dissipation and morphology with the concentration regime of nisin, in both Bacillus subtilis (lipid II rich) and Escherichia coli (lipid II impoverished), hints at a non-specific physical mechanism where degree of membrane deformation depends on degree of crowding and oligomerization of nisin.

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The Toxicity of Castor Beans and its Treatment with Doxycycline in Local Rabbits

International Journal of Pharmaceutical Quality Assurance ◽

10.25258/ijpqa.v9i2.13649 ◽

2018 ◽

Vol 9 (2) ◽

Cited By ~ 1

Author(s):

Nael Mohammed Sarheed ◽

Osamah Faisal Kokas ◽

Doaa Abd Alabas Muhammed Ridh

Keyword(s):

Castor Bean ◽

The Body ◽

Control Group ◽

High Concentration ◽

Biochemical Tests ◽

Doxycycline Treatment ◽

High Concentrations ◽

Physiological Tests ◽

Animal House ◽

Physiological And Biochemical

The plant of castor is widely spread in the Iraqi land, and characterized with containing ricin toxin, which has a very serious effects, and because the seeds of this plant scattered in the agricultural soil and rivers water, which increases the exposure of humans and animals to these beans. Objective: This experiment was designed to study the effect of high concentration of castor bean powder in some physiological and biochemical parameters and changes in some tissues of the body, as well as trying to use doxycycline to reduce the effects of ingestion of these seeds. Materials and Methods: In the experiment, 24 local rabbits were raised and fed in the Animal House of the Faculty of Medicine / Al-Muthanna University, then divided into four groups and treated for three weeks (21 days), Control group: treated with normal saline solution (0.9) orally throughout the experiment, G1: was treated orally with a concentration of 25 mg / kg of castor bean powder daily during the experiment, G2 : orally treated 25 mg / kg of castor bean and 25 mg / kg of doxycycline, G3: orally treated 25 mg / kg of castor powder with 50 mg / kg of doxycycline daily throughout the trial period. Results: The results of the experiment showed significant changes (P less than 0.05) in all physiological and biochemical blood tests when compared with control group. There was a significant decrease in PCV, Hb, RBC, T.protein and body weights, while demonstrated a significant increase in WBC, Urea, Creatinine, ALT, AST and ALP, with distortions in liver and kidney of animals that treated with Castor beans. In contrast, the treatment with doxycycline and caster beans showed significant improvement reflected by a normal proportion in physiological tests and biochemical tests with improvement in the tissues when compared to control group. Conclusions: It can be concluded from this study that castor bean has high toxic and pathogenic effects that may be dangerous to the life of the organism. Therefore, it is advisable to be cautious of these pills and avoid exposure to them, also recommended to take high concentrations of doxycycline treatment when infected with castor bean poisoning.

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The Effects of Shock Vancomycin Concentrations on the Formation of Heteroresistance in Staphylococcus aureus

Antibiotics and Chemotherapy ◽

10.37489/0235-2990-2020-65-9-10-3-7 ◽

2020 ◽

Vol 65 (9-10) ◽

pp. 3-7

Author(s):

V. V. Gostev ◽

Yu. V. Sopova ◽

O. S. Kalinogorskaya ◽

M. E. Velizhanina ◽

I. V. Lazareva ◽

...

Keyword(s):

Staphylococcus Aureus ◽

In Vitro Selection ◽

Methicillin Resistant Staphylococcus Aureus ◽

High Concentration ◽

Short Term ◽

High Concentrations ◽

Selection Of ◽

Selection Of Resistance ◽

Test Cultures

Glycopeptides are the basis of the treatment of infections caused by MRSA (Methicillin-Resistant Staphylococcus aureus). Previously, it was demonstrated that antibiotic tolerant phenotypes are formed during selection of resistance under the influence of high concentrations of antibiotics. The present study uses a similar in vitro selection model with vancomycin. Clinical isolates of MRSA belonging to genetic lines ST8 and ST239, as well as the MSSA (ATCC29213) strain, were included in the experiment. Test isolates were incubated for five hours in a medium with a high concentration of vancomycin (50 μg/ml). Test cultures were grown on the medium without antibiotic for 18 hours after each exposure. A total of ten exposure cycles were performed. Vancomycin was characterized by bacteriostatic action; the proportion of surviving cells after exposure was 70–100%. After selection, there was a slight increase in the MIC to vancomycin (MIC 2 μg/ml), teicoplanin (MIC 1.5–3 μg/ml) and daptomycin (MIC 0.25–2 μg/ml). According to the results of PAP analysis, all strains showed an increase in the area under curve depending on the concentration of vancomycin after selection, while a heteroresistant phenotype (with PAP/AUC 0.9) was detected in three isolates. All isolates showed walK mutations (T188S, D235N, E261V, V380I, and G223D). Exposure to short-term shock concentrations of vancomycin promotes the formation of heteroresistance in both MRSA and MSSA. Formation of VISA phenotypes is possible during therapy with vancomycin.

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Growth responses of periphyton and chironomids exposed to biologically treated bleached kraft pulp mill effluent

Water Science & Technology ◽

10.2166/wst.1997.0553 ◽

1997 ◽

Vol 35 (2-3) ◽

pp. 339-345 ◽

Cited By ~ 1

Author(s):

M. G. Dubé ◽

J. M. Culp

Keyword(s):

Kraft Pulp ◽

Pulp Mill ◽

Pulp Mill Effluent ◽

Growth Responses ◽

High Concentration ◽

Wood Extractives ◽

Kraft Pulp Mill ◽

Bleached Kraft Pulp ◽

Low Levels ◽

High Concentrations

Experiments were conducted in artificial streams to determine the effects of increasing concentrations of biologically treated bleached kraft pulp mill effluent (BKPME) on periphyton and chironomid growth in the Thompson River, British Columbia. Periphyton growth, as determined by increases in chlorophyll a, was significantly stimulated at all effluent concentrations tested (0.25%, 0.5%, 1.0%, 5.0% and, 10.0%). Chironomid growth (individual weight) was also significantly stimulated at low effluent concentrations (≤1.0%). At higher concentrations (5.0% and 10.0%), chironomid growth was inhibited relative to the 1.0% treatment streams. Increases in growth were attributed to the effects of nutrient and organic enrichment from BKPME. The effluent contained high concentrations of phosphorus and appears to be an important source of carbon for benthic insects grazing on the biofilm. In high concentration effluent streams, chironomid growth decreased despite low levels of typical pulp mill contaminants. This suggests that other compounds in the effluent, such as wood extractives, may be inhibiting chironomid growth. These results support findings of field monitoring studies conducted in the Thompson River where changes in periphyton and chironomid abundance occurred downstream of the bleached kraft pulp mill.

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Spatial Analysis (Measurements at Heights of 10 m and 20 m above Ground Level) of the Concentrations of Particulate Matter (PM10, PM2.5, and PM1.0) and Gaseous Pollutants (H2S) on the University Campus: A Case Study

Atmosphere ◽

10.3390/atmos12010062 ◽

2021 ◽

Vol 12 (1) ◽

pp. 62

Author(s):

Robert Cichowicz ◽

Maciej Dobrzański

Keyword(s):

Spatial Distribution ◽

Hydrogen Sulfide ◽

Particulate Matter ◽

Air Quality ◽

Spatial Analysis ◽

Ground Level ◽

Leeward Side ◽

High Concentration ◽

Above Ground Level ◽

High Concentrations

Spatial analysis of the distribution of particulate matter PM10, PM2.5, PM1.0, and hydrogen sulfide (H2S) gas pollution was performed in the area around a university library building. The reasons for the subject matter were reports related to the perceptible odor characteristic of hydrogen sulfide and a general poor assessment of air quality by employees and students. Due to the area of analysis, it was decided to perform measurements at two heights, 10 m and 20 m above ground level, using measuring equipment attached to a DJI Matrice 600 unmanned aerial vehicle (UAV). The aim of the measurements was air quality assessment and investigate the convergence of the theory of air flow around the building with the spatial distribution of air pollutants. Considerable differences of up to 63% were observed in the concentrations of pollutants measured around the building, especially between opposite sides, depending on the direction of the wind. To explain these differences, the theory of aerodynamics was applied to visualize the probable airflow in the direction of the wind. A strong convergence was observed between the aerodynamic model and the spatial distribution of pollutants. This was evidenced by the high concentrations of dust in the areas of strong turbulence at the edges of the building and on the leeward side. The accumulation of pollutants was also clearly noticeable in these locations. A high concentration of H2S was recorded around the library building on the side of the car park. On the other hand, the air turbulence around the building dispersed the gas pollution, causing the concentration of H2S to drop on the leeward side. It was confirmed that in some analyzed areas the permissible concentration of H2S was exceeded.

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ApoE4 (Δ272–299) induces mitochondrial‐associated membrane formation and mitochondrial impairment by enhancing GRP75-modulated mitochondrial calcium overload in neuron

Cell & Bioscience ◽

10.1186/s13578-021-00563-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Tao Liang ◽

Weijian Hang ◽

Jiehui Chen ◽

Yue Wu ◽

Bin Wen ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Er Stress ◽

Mitochondrial Dysfunction ◽

Mitochondrial Function ◽

Calcium Transport ◽

Calcium Overload ◽

Mitochondrial Calcium ◽

Mitochondrial Impairment

Abstract Background Apolipoprotein E4 (apoE4) is a major genetic risk factor of Alzheimer’s disease. Its C-terminal-truncated apoE4 (Δ272–299) has neurotoxicity by affecting mitochondrial respiratory function. However, the molecular mechanism(s) underlying the action of apoE4 (Δ272–299) in mitochondrial function remain poorly understood. Methods The impact of neuronal apoE4 (Δ272–299) expression on ER stress, mitochondrial-associated membrane (MAM) formation, GRP75, calcium transport and mitochondrial impairment was determined in vivo and in vitro. Furthermore, the importance of ER stress or GRP75 activity in the apoE4 (Δ272–299)-promoted mitochondrial dysfunction in neuron was investigated. Results Neuronal apoE4 (Δ272–299) expression induced mitochondrial impairment by inducing ER stress and mitochondrial-associated membrane (MAM) formation in vivo and in vitro. Furthermore, apoE4 (Δ272–299) expression promoted GRP75 expression, mitochondrial dysfunction and calcium transport into the mitochondria in neuron, which were significantly mitigated by treatment with PBA (an inhibitor of ER stress), MKT077 (a specific GRP75 inhibitor) or GRP75 silencing. Conclusions ApoE4 (Δ272–299) significantly impaired neuron mitochondrial function by triggering ER stress, up-regulating GRP75 expression to increase MAM formation, and mitochondrial calcium overload. Our findings may provide new insights into the neurotoxicity of apoE4 (Δ272–299) against mitochondrial function and uncover new therapeutic targets for the intervention of Alzheimer’s disease.

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Photocrosslinking and photopatterning of magneto-optical nanocomposite sol–gel thin film under deep-UV irradiation

Scientific Reports ◽

10.1038/s41598-021-84376-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

C. Bidaud ◽

D. Berling ◽

D. Jamon ◽

E. Gamet ◽

S. Neveu ◽

...

Keyword(s):

Uv Irradiation ◽

Cobalt Ferrite ◽

Sol Gel ◽

Optical Devices ◽

High Concentration ◽

Nanocomposite Thin Films ◽

Deep Uv ◽

High Concentrations ◽

193 Nm ◽

The Impact

AbstractThis paper is aimed at investigating the process of photocrosslinking under Deep-UV irradiation of nanocomposite thin films doped with cobalt ferrite magnetic nanoparticles (MNPs). This material is composed of a hybrid sol–gel matrix in which MNP can be introduced with high concentrations up to 20 vol%. Deep-UV (193 nm) is not only interesting for high-resolution patterning but we also show an efficient photopolymerization pathway even in the presence of high concentration of MNPs. In this study, we demonstrate that the photocrosslinking is based on the free radical polymerization of the methacrylate functions of the hybrid precursor. This process is initiated by Titanium-oxo clusters. The impact of the nanoparticles on the photopolymerization kinetic and photopatterning is investigated. We finally show that the photosensitive nanocomposite is suitable to obtain micropatterns with sub-micron resolution, with a simple and versatile process, which opens many opportunities for fabrication of miniaturized magneto-optical devices for photonic applications.

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Effects of hydrogen peroxide and hypochlorite on membrane potential of mitochondria in situ in rat heart cells

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y91-253 ◽

1991 ◽

Vol 69 (11) ◽

pp. 1705-1712 ◽

Cited By ~ 10

Author(s):

Noburu Konno ◽

K. J. Kako

Keyword(s):

Hydrogen Peroxide ◽

Membrane Potential ◽

Mitochondrial Membrane Potential ◽

Rat Heart ◽

Mitochondrial Membrane ◽

Isolated Rat Heart ◽

Heart Mitochondria ◽

High Concentrations ◽

Isolated Rat

Hydrogen peroxide (H2O2) and hypochlorite (HOCl) cause a variety of cellular dysfunctions. In this study we examined the effects of these agents on the electrical potential gradient across the inner membrane of mitochondria in situ in isolated rat heart myocytes. Myocytes were prepared by collagenase digestion and incubated in the presence of H2O2 or HOCl. Transmembrane electrical gradients were measured by distribution of [3H]triphenylmethylphosphonium+, a lipophilic cation. The particulate fraction was separated from the cytosolic compartment first by permeabilization using digitonin, followed by rapid centrifugal sedimentation through a bromododecane layer. We found that the mitochondrial membrane potential (161 ± 7 mV, negative inside) was relatively well maintained under oxidant stress, i.e., the potential was decreased only at high concentrations of HOCl and H2O2 and gradually with time. The membrane potential of isolated rat heart mitochondria was affected similarly by H2O2 and HOCl in a concentration- and time-dependent manner. High concentrations of oxidants also reduced the cellular ATP level but did not significantly change the matrix volume. When the extra-mitochondrial free calcium concentration was increased in permeabilized myocytes, the transmembrane potential was decreased proportionally, and this decrease was potentiated further by H2O2. These results support the view that heart mitochondria are equipped with well-developed defense mechanisms against oxidants, but the action of H2O2 on the transmembrane electrical gradient is exacerbated by an increase in cytosolic calcium. Keywords: ATP, calcium, cardiomyocyte, cell defense, mitochondrial membrane potential, oxidant, triphenylmethylphosphonium.

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Association of beta-cytoplasmic actin with high concentrations of acetylcholine receptor (AChR) in normal and anti-AChR-treated primary rat muscle cultures.

Journal of Histochemistry & Cytochemistry ◽

10.1177/32.9.6379042 ◽

1984 ◽

Vol 32 (9) ◽

pp. 973-981 ◽

Cited By ~ 17

Author(s):

B W Lubit

Keyword(s):

Acetylcholine Receptor ◽

Acetylcholine Receptors ◽

Neuromuscular Junctions ◽

Morphological Changes ◽

Muscle Cells ◽

High Concentration ◽

Rat Muscle ◽

Cytoplasmic Actin ◽

High Concentrations

Previous immunocytochemical studies in which an antibody specific for mammalian cytoplasmic actin was used showed that a high concentration of cytoplasmic actin exists at neuromuscular junctions of rat muscle fibers such that the distribution of actin corresponded exactly to that of the acetylcholine receptors. Although clusters of acetylcholine receptors also are present in noninnervated rat and chick muscle cells grown in vitro, neither the mechanism for the formation and maintenance of these clusters nor the relationship of these clusters to the high density of acetylcholine receptors at the neuromuscular junction in vivo are known. In the present study, a relationship between beta-cytoplasmic actin and acetylcholine receptors in vitro has been demonstrated immunocytochemically using an antibody specific for the beta-form of cytoplasmic actin. Networks of cytoplasmic actin-containing filaments were found in discrete regions of the myotube membrane that also contained high concentrations of acetylcholine receptors; such high concentrations of acetylcholine receptors have been described in regions of membrane-substrate contact. Moreover, when primary rat myotubes were exposed to human myasthenic serum, gross morphological changes, accompanied by an apparent rearrangement of the cytoplasmic actin-containing cytoskeleton, were produced. Although whether the distribution of cytoplasmic actin-containing structures was influenced by the organization of acetylcholine receptor or vice versa cannot be determined from these studies, these findings suggest that in primary rat muscle cells grown in vitro, acetylcholine receptors and beta-cytoplasmic actin-containing structures may be somehow connected.

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