Abstract 438: Hydrogen Sulfide Promotes Mitochondrial Biogenesis Through the Regulation of AMP-activated Protein Kinase

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Yuuki Shimizu ◽  
Rohini Polavarapu ◽  
John Calvert
Keyword(s):  
Hydrogen Sulfide ◽  
Mitochondrial Biogenesis ◽  
Target Genes ◽  
Nuclear Dna ◽  
Citrate Synthase ◽  
Serine Phosphorylation ◽  
Signaling Cascade ◽  
Disease States ◽  
Upstream Kinase ◽  
High Concentrations

Background: Hydrogen sulfide (H 2 S) possesses numerous cellular actions that account for its cardioprotective effects. A mechanism of particular interest is its effects on the mitochondria. At low concentrations, H 2 S donates electrons to the electron transport chain, whereas at high concentrations it inhibits mitochondrial respiration. H 2 S therapy improves mitochondrial function and prevents the loss of mitochondria following the onset of myocardial ischemia. However, it is not known if these improvements are associated with simply a reduction in injury or if mitochondrial biogenesis is involved. Therefore, the purpose of this study was to determine if H 2 S regulates/induces mitochondrial biogenesis in the heart. Methods and Results: C57BL/6J mice (8 weeks of age) were given an orally active H 2 S donor (SG-1002; 20 mg/kg/day) in their chow for 4 weeks. For these studies we focused our analysis on an AMPK-PGC1α signaling cascade. SG-1002 significantly increased the phosphorylation of AMPK, the serine phosphorylation of PGC1α, and increased the nuclear localization of PGC1α. This was associated with an increase in the gene expression of PGC1α target genes associated with mitochondrial biogenesis, an increase in mitochondrial to nuclear DNA ratios and an increase in citrate synthase activity. SG-1002 failed to elicit these changes in AMPK deficient mice. Therefore, we sought to determine how SG-1002 activated AMPK. SG-1002 did not alter the phosphorylation of LKB1, an upstream kinase of AMPK, and did not alter the levels of AMP (activator of AMPK). SG-1002 did not alter the expression of protein phosphatase 2A (PP2A; dephosphorylates AMPK), but it did significantly decrease the activity of PP2A). This decrease was accompanied by an increase in the sulfhydration of PP2A, suggesting that this modification is inhibitory. Conclusion: These data suggest that H 2 S augments mitochondrial biogenesis in the heart via an AMPK-PGC1α signaling cascade. This is important because mitochondrial abnormalities are associated with a number of disease states (diabetes and heart failure) where H 2 S levels are decreased. Therefore, strategies aimed at increasing H 2 S levels could potentially induce the generation of new, healthy mitochondria.

Schisandrin Restores the Amyloid β-Induced Impairments on Mitochondrial Function, Energy Metabolism, Biogenesis, and Dynamics in Rat Primary Hippocampal Neurons

Pharmacology ◽  
2021 ◽  
pp. 1-11
Author(s):  
Zhongyuan Piao ◽  
Lin Song ◽  
Lifen Yao ◽  
Limei Zhang ◽  
Yichan Lu
Keyword(s):  
Energy Metabolism ◽  
Cytochrome C ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Function ◽  
Hippocampal Neurons ◽  
Citrate Synthase ◽  
Mitochondrial Permeability Transition ◽  
Amyloid Β ◽  
Mitochondrial Functions ◽  
Primary Hippocampal Neurons

Introduction: Schisandrin which is derived from Schisandra chinensis has shown multiple pharmacological effects on various diseases including Alzheimer’s disease (AD). It is demonstrated that mitochondrial dysfunction plays an essential role in the pathogenesis of neurodegenerative disorders. Objective: Our study aims to investigate the effects of schisandrin on mitochondrial functions and metabolisms in primary hippocampal neurons. Methods: In our study, rat primary hippocampal neurons were isolated and treated with indicated dose of amyloid β1–42 (Aβ1–42) oligomer to establish a cell model of AD in vitro. Schisandrin (2 μg/mL) was further subjected to test its effects on mitochondrial function, energy metabolism, mitochondrial biogenesis, and dynamics in the Aβ1–42 oligomer-treated neurons. Results and Conclusions: Our findings indicated that schisandrin significantly alleviated the Aβ1–42 oligomer-induced loss of mitochondrial membrane potential and impaired cytochrome c oxidase activity. Additionally, the opening of mitochondrial permeability transition pore and release of cytochrome c were highly restricted with schisandrin treatment. Alterations in cell viability, ATP production, citrate synthase activity, and the expressions of glycolysis-related enzymes demonstrated the relief of defective energy metabolism in Aβ-treated neurons after the treatment of schisandrin. For mitochondrial biogenesis, elevated expression of peroxisome proliferator-activated receptor γ coactivator along with promoted mitochondrial mass was found in schisandrin-treated cells. The imbalance in the cycle of fusion and fission was also remarkably restored by schisandrin. In summary, this study provides novel mechanisms for the protective effect of schisandrin on mitochondria-related functions.

scholarly journals 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 ◽  
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.

scholarly journals An exploratory assessment of the applicability of direct-to-consumer genetic testing to translational research in Japan

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Masahiro Inoue ◽  
Shota Arichi ◽  
Tsuyoshi Hachiya ◽  
Anna Ohtera ◽  
Seok-Won Kim ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Translational Research ◽  
Drug Target ◽  
Target Genes ◽  
Healthy Individuals ◽  
Alcohol Sensitivity ◽  
Direct To Consumer ◽  
Disease States ◽  
Multiple Phenotypes ◽  
Related Phenotype

Abstract Objective In order to assess the applicability of a direct-to-consumer (DTC) genetic testing to translational research for obtaining new knowledge on relationships between drug target genes and diseases, we examined possibility of these data by associating SNPs and disease related phenotype information collected from healthy individuals. Results A total of 12,598 saliva samples were collected from the customers of commercial service for SNPs analysis and web survey were conducted to collect phenotype information. The collected dataset revealed similarity to the Japanese data but distinguished differences to other populations of all dataset of the 1000 Genomes Project. After confirmation of a well-known relationship between ALDH2 and alcohol-sensitivity, Phenome-Wide Association Study (PheWAS) was performed to find association between pre-selected drug target genes and all the phenotypes. Association was found between GRIN2B and multiple phenotypes related to depression, which is considered reliable based on previous reports on the biological function of GRIN2B protein and its relationship with depression. These results suggest possibility of using SNPs and phenotype information collected from healthy individuals as a translational research tool for drug discovery to find relationship between a gene and a disease if it is possible to extract individuals in pre-disease states by properly designed questionnaire.

Curcumin induces mitochondrial biogenesis by increasing cAMP levels via PDE4A inhibition in skeletal muscle

2021 ◽  
pp. 1-34
Author(s):  
Hamidie Ronald D Ray ◽  
Tsubasa Shibaguchi ◽  
Tatsuya Yamada ◽  
Rikuhide Koma ◽  
Rie Ishizawa ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Expression ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Respiration ◽  
Citrate Synthase ◽  
Signalling Pathway ◽  
Curcumin Treatment ◽  
Camp Content ◽  
Signalling Molecules ◽  
Camp Levels

Abstract Background: Previous research has suggested that curcumin potentially induces mitochondrial biogenesis in skeletal muscle via increasing cAMP levels. However, the regulatory mechanisms for this phenomenon remain unknown. The purpose of the present study was to clarify the mechanism by which curcumin activates cAMP-related signalling pathways that upregulate mitochondrial biogenesis and respiration in skeletal muscle. Methods: The effect of curcumin treatment (i.p., 100 mg/kg-BW/day for 28 days) on mitochondrial biogenesis was determined in rats. The effects of curcumin and exercise (swimming for 2 h/day for 3 days) on the cAMP signalling pathway were determined in the absence and presence of phosphodiesterase (PDE) or protein kinase A (PKA) inhibitors. Mitochondrial respiration, citrate synthase (CS) activity, cAMP content, and protein expression of cAMP/PKA signalling molecules were analysed. Results: Curcumin administration increased COX-IV protein expression, and CS and complex I activity, consistent with the induction of mitochondrial biogenesis by curcumin. Mitochondrial respiration was not altered by curcumin treatment. Curcumin and PDE inhibition tended to increase cAMP levels with or without exercise. In addition, exercise increased the phosphorylation of PDE4A, whereas curcumin treatment strongly inhibited PDE4A phosphorylation regardless of exercise. Furthermore, curcumin promoted AMPK phosphorylation and PGC-1α deacetylation. Inhibition of PKA abolished the phosphorylation of AMPK. Conclusion: The present results suggest that curcumin increases cAMP levels via inhibition of PDE4A phosphorylation, which induces mitochondrial biogenesis through a cAMP/PKA/AMPK signalling pathway. Our data also suggest the possibility that curcumin utilizes a regulatory mechanism for mitochondrial biogenesis that is distinct from the exercise-induced mechanism in skeletal muscle.

The Pleiotropic Intricacies of Hedgehog Signaling: From Craniofacial Patterning to Carcinogenesis

FACE ◽  
2021 ◽  
pp. 273250162110243
Author(s):  
Mikhail Pakvasa ◽  
Andrew B. Tucker ◽  
Timothy Shen ◽  
Tong-Chuan He ◽  
Russell R. Reid
Keyword(s):  
Intracellular Signaling ◽  
Limb Development ◽  
Hedgehog Signaling ◽  
Target Genes ◽  
Craniofacial Development ◽  
Signaling Cascade ◽  
Signaling Mechanisms ◽  
Intracellular Signaling Cascade ◽  
And Function

Hedgehog signaling was discovered more than 40 years ago in experiments demonstrating that it is a fundamental mediator of limb development. Since that time, it has been shown to be important in development, homeostasis, and disease. The hedgehog pathway proceeds through a pathway highly conserved throughout animals beginning with the extracellular diffusion of hedgehog ligands, proceeding through an intracellular signaling cascade, and ending with the activation of specific target genes. A vast amount of research has been done elucidating hedgehog signaling mechanisms and regulation. This research has found a complex system of genetics and signaling that helps determine how organisms develop and function. This review provides an overview of what is known about hedgehog genetics and signaling, followed by an in-depth discussion of the role of hedgehog signaling in craniofacial development and carcinogenesis.

scholarly journals Preconditioning Mediated by Sublethal Oxygen—Glucose Deprivation-Induced Cyclooxygenase-2 Expression via the Signal Transducers and Activators of Transcription 3 Phosphorylation

2008 ◽  
Vol 28 (7) ◽  
pp. 1329-1340 ◽  
Author(s):  
Eun J Kim ◽  
Ami P Raval ◽  
Miguel A Perez-Pinzon
Keyword(s):  
Glucose Deprivation ◽  
Cyclooxygenase 2 ◽  
Serine Phosphorylation ◽  
Signaling Cascade ◽  
Oxygen Glucose Deprivation ◽  
Signal Transducers ◽  
Extracellular Signal ◽  
Cox 2 ◽  
Transcription 3 ◽  
Signal Transducers And Activators

The signal transducers and activators of transcription (STATs) were found to be essential for cardioprotection. However, their role in preconditioning (PC) neuroprotection remains undefined. Previously, our studies showed that PC mediated a signaling cascade that involves activation of epsilon protein kinase C (εPKC), extracellular signal-regulated kinase (ERK1/2), and cyclooxygenase-2 (COX-2) pathways. However, the intermediate pathway by which ERK1/2 activates COX-2 was not defined. In this study, we investigated whether the PC-induced signaling pathway requires phosphorylation of STAT isoforms for COX-2 expression. To mimic PC or lethal ischemia, mixed cortical neuron/astrocyte cell cultures were subjected to 1 and/or 4 h of oxygen—glucose deprivation (OGD), respectively. The results indicated serine phosphorylation of STAT3 after PC or εPKC activation. Inhibition of either εPKC or ERK1/2 activation abolished PC-induced serine phosphorylation of STAT3. Additionally, inhibition of STAT3 prevented PC-induced COX-2 expression and neuroprotection against OGD. Therefore, our findings suggest that PC signaling cascade involves STAT3 activation after εPKC and ERK1/2 activation. Finally, we show that STAT3 activation mediates COX-2 expression and ischemic tolerance.

scholarly journals Exercise training enhances white adipose tissue metabolism in rats selectively bred for low- or high-endurance running capacity

2013 ◽  
Vol 305 (3) ◽  
pp. E429-E438 ◽  
Author(s):  
Erin J. Stephenson ◽  
Sarah J. Lessard ◽  
Donato A. Rivas ◽  
Matthew J. Watt ◽  
Ben B. Yaspelkis ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Exercise Training ◽  
White Adipose Tissue ◽  
Citrate Synthase ◽  
Mitochondrial Protein ◽  
Treadmill Running ◽  
Endurance Running ◽  
Insulin Resistant ◽  
Disease States ◽  
Hcr Model

Impaired visceral white adipose tissue (WAT) metabolism has been implicated in the pathogenesis of several lifestyle-related disease states, with diminished expression of several WAT mitochondrial genes reported in both insulin-resistant humans and rodents. We have used rat models selectively bred for low- (LCR) or high-intrinsic running capacity (HCR) that present simultaneously with divergent metabolic phenotypes to test the hypothesis that oxidative enzyme expression is reduced in epididymal WAT from LCR animals. Based on this assumption, we further hypothesized that short-term exercise training (6 wk of treadmill running) would ameliorate this deficit. Approximately 22-wk-old rats (generation 22) were studied. In untrained rats, the abundance of mitochondrial respiratory complexes I–V, citrate synthase (CS), and PGC-1 was similar for both phenotypes, although CS activity was greater than 50% in HCR ( P = 0.09). Exercise training increased CS activity in both phenotypes but did not alter mitochondrial protein content. Training increased the expression and phosphorylation of proteins with roles in β-adrenergic signaling, including β3-adrenergic receptor (16% increase in LCR; P < 0.05), NOR1 (24% decrease in LCR, 21% decrease in HCR; P < 0.05), phospho-ATGL (25% increase in HCR; P < 0.05), perilipin (25% increase in HCR; P < 0.05), CGI-58 (15% increase in LCR; P < 0.05), and GLUT4 (16% increase in HCR; P < 0.0001). A training effect was also observed for phospho-p38 MAPK (12% decrease in LCR, 20% decrease in HCR; P < 0.05) and phospho-JNK (29% increase in LCR, 20% increase in HCR; P < 0.05). We conclude that in the LCR-HCR model system, mitochondrial protein expression in WAT is not affected by intrinsic running capacity or exercise training. However, training does induce alterations in the activity and expression of several proteins that are essential to the intracellular regulation of WAT metabolism.

Abstract 206: Accumulation of Mitochondrial DNA Mutations Impairs Survival, Proliferation, and Differentiation of Cardiac Progenitor Cells

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Amabel M Orogo ◽  
Dieter A Kubli ◽  
Anne N Murphy ◽  
Åsa B Gustafsson
Keyword(s):  
Mitochondrial Dna ◽  
Progenitor Cells ◽  
Mitochondrial Biogenesis ◽  
Nuclear Dna ◽  
Critical Role ◽  
Chemotherapeutic Agents ◽  
Cardiac Progenitor Cells ◽  
Mtdna Mutations ◽  
Differentiation Medium ◽  
Proliferation And Differentiation

Activation and participation of cardiac progenitor cells (CPCs) in regeneration are critical for effective repair in the wake of pathologic injury. Stem cell activation and commitment involve increased energy demand and mitochondrial biogenesis. To date, little attention has been paid to the importance of mitochondria in CPC survival, proliferation and differentiation. CPC function is reduced with age but the underlying mechanism is still unclear. Mitochondrial DNA (mtDNA) is more susceptible to oxidative attacks than nuclear DNA due to its proximity to the mitochondrial respiratory chain and lack of protective histone-like proteins. With age, mtDNA accumulates mutations that can impair mitochondrial respiration and increase ROS production. In this study, we examined the effects of accumulating mtDNA mutations on CPC proliferation and survival. We have found that incubation of uncommitted c-kit+ CPCs in differentiation medium increased mitochondrial mass and expansion of the mitochondrial network, which correlated with increased cell size and expression of cardiac lineage commitment markers. Differentiation activated mitochondrial biogenesis, increased mtDNA copy number, and enhanced oxidative capacity and cellular ATP levels in CPCs. To investigate the effect of mtDNA mutations and aging on CPC survival and function, we utilized a mouse model in which a mutation in the mtDNA polymerase γ (POLG m/m ) leads to accumulation of mtDNA mutations, mitochondrial dysfunction, and accelerated aging. Isolated CPCs from hearts of 2-month old POLG m/m mice had reduced proliferation and were more susceptible to oxidative stress and chemotherapeutic agents compared to WT CPCs. The majority of POLG m/m CPCs contained fragmented mitochondria as shown by immunostaining. Incubation in differentiation medium resulted in fewer GATA-4 positive POLG m/m CPCs compared to WT CPCs. The reduced differentiation in these POLG m/m CPCs correlated with reduced PGC-1α expression and OXPHOS protein levels, suggesting that mitochondrial biogenesis is impaired. These data demonstrate that mitochondria play a critical role in CPC function, and accumulation of mtDNA mutations impairs CPC function and reduces their repair potential.

scholarly journals COMPORTAMIENTO DE TORRE DE LAVADO A NIVEL DE ESCALA PARA LA REMOCIÓN DE H2S DE UN REACTOR ANAEROBICO DE FLUJO ASCENDENTE

2018 ◽  
Vol 27 (1) ◽  
pp. 85
Author(s):  
José A. Acaro R ◽  
Jeannie L. Quispe E. ◽  
Mali I. Salas D.
Keyword(s):  
Hydrogen Sulfide ◽  
Dissolved Oxygen ◽  
Coming Out ◽  
Packed Bed ◽  
Uasb Reactor ◽  
Sulfate Concentration ◽  
Hydrogen Sulfide Removal ◽  
Palabras Clave ◽  
Wet Scrubber ◽  
High Concentrations

Nuestro equipo en esta oportunidad hizo una simulación de una torre de lavado, la cual la aplicamos en el reactor UASB, a manera de escala construimos una torre de lavado compuesta por difusores, una cama de sólidos hecha de material de esponja, un tubo de acrílico y todas las conexiones que conducen el biogás con H2S. Los componentes a eliminar y/o remover fueron los gases que salen del reactor, en especial del H2S (gas odorífero y toxico que a grandes concentraciones pude llevar a la muerte y como resultado de sus reacciones con el ambiente puede causar daños en las estructuras con la cual este en contacto) mediante la oxidación con el oxígeno disuelto que proveen las microalgas presentes en el agua de la laguna terciara utilizada. Esta torre de lavado la montamos en las instalaciones de CITRAR‐UNI con el permiso del operador y vimos el comportamiento que tiene esta torre, mediante los monitoreos de oxígeno disuelto, temperatura, pH y sulfatos que realizamos durante tres semanas de monitoreo. Como resultados obtuvimos que la torre de lavado sí oxidaba y removía la contracción de H2S, ya que cuando pasaba el tiempo se consumía el oxígeno disuelto, además de esto también en el monitoreo de sulfatos pudimos observar un aumento de este parámetro es decir la torre si estaba consumiendo en H2S, y por esta razón también disminuyo el olor fétido que produce este gas. Palabras clave.- Torre de lavado, reactor UASB, remoción de sulfuro de hidrógeno. ABSTRACT The present work reports the simulation of a wet scrubber coupled to an UASB reactor. The scrubber consisted of baffles, packed bed of sponge material, an acrylic tube and all the connections necessary to bring the H2S‐ladden biogas. The purpose of the equipment is to eliminate some of the gases coming out of the reactor, through their oxidation by the dissolved oxygen provided by the microalgae present in the water from the tertiary lagoon. Hydrogen sulfide is a foul‐ smelling and toxic gas which can cause death at high concentrations, and can also cause damage to the structures with which it comes into contact. The scrubber was installed on the site of CITRAR‐UNI and the behavior of the equipment was monitored during three weeks by following the temperature, pH and the concentrations of sulfates and dissolved oxygen. The results have shown that the scrubber was effectively an oxidizing environment which was removing H2S, since the dissolved oxygen was actually consumed gradually. It was also observed that the sulfate concentration was increasing, indicating a consumption of H2S, which was also confirmed by a reduction in the odor of the gas. Keywords.- scrubber, UASB reactor, hydrogen sulfide removal .

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