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Mitochondria cAMP

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https://www.readbyqxmd.com/read/28928268/mild-acidosis-delays-neutrophil-apoptosis-via-multiple-signaling-pathways-and-acts-in-concert-with-inflammatory-mediators
#1
Driss El Kebir, Everton de Oliveira Lima Dos Santos, Soukaina Mansouri, Meriem Sekheri, János G Filep
Accumulating evidence indicates development of local extracellular acidosis in inflamed tissues in response to infection and tissue injury. Activation of infiltrating neutrophils contributes to a transient decrease in pH, which, in turn, triggers innate immunity. In this study, we investigated the impact of extracellular acidosis on neutrophil apoptosis, a critical determinant of the outcome of the inflammatory response and analyzed the underlying signaling pathways. Culture of human isolated neutrophils in mildly acidotic conditions (pH 6...
September 19, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28923495/crispr-cas9-engineering-of-adult-mouse-liver-demonstrates-that-the-dnajb1-prkaca-gene-fusion-is-sufficient-to-induce-tumors-resembling-fibrolamellar-hepatocellular-carcinoma
#2
Lars H Engelholm, Anjum Riaz, Denise Serra, Frederik Dagnæs-Hansen, Jens V Johansen, Eric Santoni-Rugiu, Steen H Hansen, Francesco Niola, Morten Frödin
BACKGROUND & AIMS: Fibrolamellar hepatocellular carcinoma (FL-HCC) is a primary liver cancer that predominantly affects young adults with no underlying liver disease. A somatic, 400 Kb deletion on chromosome 19 that fuses part of the DnaJ heat shock protein family (Hsp40) member B1 gene (DNAJB1) to the protein kinase cAMP-activated catalytic subunit alpha gene (PRKACA) has been repeatedly identified in patients with FL-HCC. However, the DNAJB1-PRKACA gene fusion has not been shown to induce liver tumorigenesis...
September 15, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28864766/distinct-intracellular-sac-camp-domains-regulate-er-calcium-signaling-and-oxphos-function
#3
Federica Valsecchi, Csaba Konrad, Marilena D'Aurelio, Lavoisier S Ramos-Espiritu, Anna Stepanova, Suzanne R Burstein, Alexander Galkin, Jordi Magranè, Anatoly Starkov, Jochen Buck, Lonny R Levin, Giovanni Manfredi
cAMP regulates a wide variety of physiological functions in mammals. This single second messenger can regulate multiple, seemingly disparate functions within independently regulated cell compartments. We previously identified one such compartment inside the matrix of the mitochondria, where soluble adenylyl cyclase (sAC) regulates oxidative phosphorylation (OXPHOS). We now show that sAC KO fibroblasts have a defect in OXPHOS activity and attempt to compensate for this defect by increasing OXPHOS proteins. Importantly, sAC KO cells also exhibit decreased probability of endoplasmic reticulum (ER) Ca(2+) release associated with diminished phosphorylation of the inositol 3-phosphate receptor...
September 1, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28820402/does-signaling-of-estrogen-related-receptors-affect-structure-and-function-of-bank-vole-leydig-cells
#4
P Pawlicki, A Milon, M Zarzycka, J Galas, W Tworzydlo, A Kaminska, L Pardyak, K Lesniak, A Pacwa, B Bilinska, E Gorowska-Wojtowicz, M Kotula-Balak
To get a deeper insight into the function of estrogen-related receptors (ERRs) and dissect underlying mechanism in Leydig cells, ERRs (type α, β and γ) were blocked or activated in testes of adult bank voles (Myodes glareolus) which show seasonal changes in the intratesticular sex hormones level. Both actively reproducing animals (long day conditions; LD) and those with regression of the reproductive system (short day conditions; SD) received intraperitoneal injections of selective ERRα antagonist 3-[4-(2,4-Bis-trifluoromethylbenzyloxy)-3-methoxyphenyl]-2-cyano-N-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)acrylamide (XCT 790) or selective ERRβ/ERRγ agonist N-(4-(Diethylaminobenzylidenyl)-N'-(4-hydroxybenzoyl)-hydrazine (DY131) (50 μ/kg bw; six doses every other day)...
June 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28761415/dual-and-multi-drug-delivery-nanoparticles-towards-neuronal-survival-and-synaptic-repair
#5
REVIEW
Angelina Angelova, Borislav Angelov
Among the macromolecular drug targets in neurodegenerative disorders, the neurotrophin brain-derived neurotrophic factor (BDNF) and its high-affinity tropomyosin-related kinase receptor (TrkB) present strong interest for nanomedicine development aiming at neuronal and synaptic repair. Currently, BDNF is regarded as the neurotrophic factor of highest therapeutic significance. However, BDNF has delivery problems as a protein drug. The enhanced activation of the transcription factor CREB (cAMP response element-binding protein) has been evidenced to increase the BDNF gene expression and hence the production of endogenous BDNF...
June 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28747539/steroidogenesis-in-leydig-cells-effects-of-aging-and-environmental-factors
#6
Yiyan Wang, Fenfen Chen, Leping Ye, B R Zirkin, H Chen
Serum testosterone (T) levels decrease with aging in both humans and rodents. Using the rat as a model system, it was found that age-related reductions in serum T were not due to loss of Leydig cells, but rather to the reduced ability of the Leydig cells to produce T in response to luteinizing hormone (LH). Detailed analyses of the steroidogenic pathway have suggested that two defects along the pathway, LH stimulated cAMP production and cholesterol transport to and into the mitochondria, are of particular importance in age-related reductions in T production...
July 26, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28669047/melatonin-protected-cardiac-microvascular-endothelial-cells-against-oxidative-stress-injury-via-suppression-of-ip3r-ca-2-c-vdac-ca-2-m-axis-by-activation-of-mapk-erk-signaling-pathway
#7
Hang Zhu, Qinhua Jin, Yang Li, Qiang Ma, Jing Wang, Dandan Li, Hao Zhou, Yundai Chen
The cardiac microvascular reperfusion injury is characterized by the microvascular endothelial cells (CMECs) oxidative damage which is responsible for the progression of cardiac dysfunction. However, few strategies are available to reverse such pathologies. This study aimed to explore the mechanism by which oxidative stress induced CMECs death and the beneficial actions of melatonin on CMECs survival, with a special focused on IP3R-[Ca(2+)]c/VDAC-[Ca(2+)]m damage axis and the MAPK/ERK survival signaling. We found that oxidative stress induced by H2O2 significantly activated cAMP response element binding protein (CREB) that enhanced IP3R and VDAC transcription and expression, leading to [Ca(2+)]c and [Ca(2+)]m overload...
July 1, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28668616/influence-of-flavonols-and-quercetin-derivative-compounds-on-ma-10-leydig-cells-steroidogenic-genes-expressions
#8
Michelle Cormier, Firas Ghouili, Pauline Roumaud, Luc J Martin, Mohamed Touaibia
Androgen are mainly synthesized and secreted from testicular Leydig cells and play critical roles in testis development, normal masculinization, spermatogenesis, and male fertility. The rate-limiting step in testosterone biosynthesis involves the import of cholesterol inside mitochondria by the steroidogenic acute regulatory (Star) protein. Cholesterol is then converted to pregnenolone by the steroidogenic enzyme Cyp11a1, followed by a chemical transformation to testosterone using other steroidogenic enzymes...
October 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28619991/evidence-that-differentiation-inducing-factor-1-controls-chemotaxis-and-cell-differentiation-at-least-in-part-via-mitochondria-in-d-discoideum
#9
Yuzuru Kubohara, Haruhisa Kikuchi, Van Hai Nguyen, Hidekazu Kuwayama, Yoshiteru Oshima
Differentiation-inducing factor-1 [1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl)hexan-1-one (DIF-1)] is an important regulator of cell differentiation and chemotaxis in the development of the cellular slime mold Dictyostelium discoideum However, the entire signaling pathways downstream of DIF-1 remain to be elucidated. To characterize DIF-1 and its potential receptor(s), we synthesized two fluorescent derivatives of DIF-1, boron-dipyrromethene (BODIPY)-conjugated DIF-1 (DIF-1-BODIPY) and nitrobenzoxadiazole (NBD)-conjugated DIF-1 (DIF-1-NBD), and investigated their biological activities and cellular localization...
June 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28569781/mitochondrial-akap1-supports-mtor-pathway-and-tumor-growth
#10
Laura Rinaldi, Maria Sepe, Rossella Delle Donne, Kristel Conte, Antonietta Arcella, Domenica Borzacchiello, Stefano Amente, Fernanda De Vita, Monia Porpora, Corrado Garbi, Maria A Oliva, Claudio Procaccini, Deriggio Faicchia, Giuseppe Matarese, Federica Zito Marino, Gaetano Rocco, Sara Pignatiello, Renato Franco, Luigi Insabato, Barbara Majello, Antonio Feliciello
Mitochondria are the powerhouses of energy production and the sites where metabolic pathway and survival signals integrate and focus, promoting adaptive responses to hormone stimulation and nutrient availability. Increasing evidence suggests that mitochondrial bioenergetics, metabolism and signaling are linked to tumorigenesis. AKAP1 scaffolding protein integrates cAMP and src signaling on mitochondria, regulating organelle biogenesis, oxidative metabolism and cell survival. Here, we provide evidence that AKAP1 is a transcriptional target of Myc and supports the growth of cancer cells...
June 1, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28552530/different-roles-of-%C3%AE-arrestin-and-the-pka-pathway-in-mitochondrial-ros-production-induced-by-acute-%C3%AE-adrenergic-receptor-stimulation-in-neonatal-mouse-cardiomyocytes
#11
Jianshu Zhang, Han Xiao, Jing Shen, Nanping Wang, Youyi Zhang
Reactive oxygen species (ROS) play a crucial role in various physiological and pathological processes mediated by β-adrenergic receptors (β-ARs) in cardiomyocytes. However, the sources and signaling pathways involved in ROS production induced by acute β-AR activation have not yet been fully defined. In primary neonatal mouse cardiomyocytes (NMCMs), the β-AR agonist isoproterenol (ISO) induced a rapid increase in mitochondrial ROS and total ROS production. Both the expression and activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2/4 (NOX 2/4) remained unchanged after 2 h of ISO treatment, suggesting that acute ISO stimulation mainly induces mitochondrial ROS production in NMCMs...
August 5, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28501614/shaping-mitochondrial-dynamics-the-role-of-camp-signalling
#12
Giulietta Di Benedetto, Andrea Gerbino, Konstantinos Lefkimmiatis
In recent years, our idea of mitochondria evolved from "mere" energy and metabolite producers to key regulators of many cellular functions. In order to preserve and protect their functional status, these organelles engage a number of dynamic processes that allow them to decrease accumulated burden and maintain their homeostasis. Indeed, mitochondria can unite (fusion), divide (fission), position themselves strategically in the cell (motility/trafficking) and if irreversibly damaged or dysfunctional eliminated (mitophagy)...
May 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28500222/energy-requirements-of-odor-transduction-in-the-chemosensory-cilia-of-olfactory-sensory-neurons-rely-on-oxidative-phosphorylation-and-glycolytic-processing-of-extracellular-glucose
#13
Pablo S Villar, Ricardo Delgado, Cecilia Vergara, Juan G Reyes, Juan Bacigalupo
The mechanisms that power the physiological events occurring in cilia, flagella, and microvilli are of fundamental importance for the functions of these important and ubicuous organelles. The olfactory epithelium is mostly populated by ciliated olfactory sensory neurons (OSNs) and surrounding sustentacular cells (SCs) with apical microvilli. The only OSN dendrite extends to the surface forming a knob projecting several chemosensory cilia of ∼50 × 0.2 μm, devoid of inner membranes embedded in a mucus layer...
June 7, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28493341/design-and-validation-of-the-first-cell-impermeant-melatonin-receptor-agonist
#14
Florence Gbahou, Erika Cecon, Guillaume Viault, Romain Gerbier, Frederic Jean-Alphonse, Angeliki Karamitri, Gérald Guillaumet, Philippe Delagrange, Robert M Friedlander, Jean-Pierre Vilardaga, Franck Suzenet, Ralf Jockers
BACKGROUND AND PURPOSE: The paradigm that GPCRs are able to prolong or initiate cellular signalling through intracellular receptors recently emerged. Melatonin binds to G protein-coupled MT1 and MT2 receptors. In contrast to most other hormones targeting GPCRs, melatonin and its synthetic analogues are amphiphilic molecules easily penetrating into cells, but the existence of intracellular receptors is still unclear mainly due to a lack of appropriate tools. EXPERIMENTAL APPROACH: We therefore designed and synthesized a series of hydrophilic melatonin receptor ligands coupled to the Cy3 cyanin fluorophore to reliably monitor its inability to penetrate cells...
July 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28479382/characterization-and-expression-of-star2a-and-star2b-in-the-olive-flounder-paralichthys-olivaceus
#15
Dongdong Liang, Zhaofei Fan, Shenda Weng, Shuang Jiao, Zhihao Wu, Yuxia Zou, Xungang Tan, Jun Li, Peijun Zhang, Feng You
Steroidogenic acute regulatory protein 2 (StAR2) is a key protein in transporting cholesterol from the outer mitochondria membrane to the inner mitochondria membrane for sex steroid synthesis. In this study, two StAR2 gene isoforms, StAR2a and StAR2b, were isolated from the olive flounder Paralichthys olivaceus gonads. Semi-quantitative RT-PCR results indicated that their expression levels were higher in testis than those in ovary. StAR2a was mainly expressed in the thecal cells and ooplasm of ovary, and Leydig cells and spermatid of testis according to the results of in situ hybridization...
August 30, 2017: Gene
https://www.readbyqxmd.com/read/28463107/pde2a2-regulates-mitochondria-morphology-and-apoptotic-cell-death-via-local-modulation-of-camp-pka-signalling
#16
Stefania Monterisi, Miguel J Lobo, Craig Livie, John C Castle, Michael Weinberger, George Baillie, Nicoletta C Surdo, Nshunge Musheshe, Alessandra Stangherlin, Eyal Gottlieb, Rory Maizels, Mario Bortolozzi, Massimo Micaroni, Manuela Zaccolo
cAMP/PKA signalling is compartmentalised with tight spatial and temporal control of signal propagation underpinning specificity of response. The cAMP-degrading enzymes, phosphodiesterases (PDEs), localise to specific subcellular domains within which they control local cAMP levels and are key regulators of signal compartmentalisation. Several components of the cAMP/PKA cascade are located to different mitochondrial sub-compartments, suggesting the presence of multiple cAMP/PKA signalling domains within the organelle...
May 2, 2017: ELife
https://www.readbyqxmd.com/read/28457938/parp-inhibition-protects-mitochondria-and-reduces-ros-production-via-parp-1-atf4-mkp-1-mapk-retrograde-pathway
#17
Eniko Hocsak, Viktor Szabo, Nikoletta Kalman, Csenge Antus, Anna Cseh, Katalin Sumegi, Krisztian Eros, Zoltan Hegedus, Ferenc Gallyas, Balazs Sumegi, Boglarka Racz
Oxidative stress induces DNA breaks and PARP-1 activation which initiates mitochondrial reactive oxygen species (ROS) production and cell death through pathways not yet identified. Here, we show the mechanism by which PARP-1 influences these processes via PARylation of activating transcription factor-4 (ATF4) responsible for MAP kinase phosphatase-1 (MKP-1) expression and thereby regulates MAP kinases. PARP inhibitor, or silencing, of PARP induced MKP-1 expression by ATF4-dependent way, and inactivated JNK and p38 MAP kinases...
April 27, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28455626/influences-of-flavones-on-cell-viability-and-camp-dependent-steroidogenic-gene-regulation-in-ma-10-leydig-cells
#18
Michelle Cormier, Firas Ghouili, Pauline Roumaud, William Bauer, Mohamed Touaibia, Luc J Martin
Testicular Leydig cells are major contributors of androgen synthesis and secretion, which play an important role in testis development, normal masculinization, maintenance of spermatogenesis, and general male fertility. The rate-limiting step in testosterone biosynthesis involves the transfer of cholesterol to the mitochondrial inner membrane by the steroidogenic acute regulatory (Star) protein, a critical factor in steroid hormone biosynthesis. Once inside the mitochondria, cholesterol is metabolized by the steroidogenic enzyme Cyp11a1 to pregnenolone, which is further converted to testosterone by the action of other steroidogenic enzymes...
April 28, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28395332/acetamiprid-inhibits-testosterone-synthesis-by-affecting-the-mitochondrial-function-and-cytoplasmic-adenosine-triphosphate-production-in-rat-leydig-cells%C3%A2
#19
Deying Kong, Jidong Zhang, Xiaohui Hou, Shibin Zhang, Jun Tan, Yuanshou Chen, Weirong Yang, Junwei Zeng, Yong Han, Xiaohong Liu, Delin Xu, Renlian Cai
The insecticide acetamiprid is used to control noxious agricultural pests. However, it can cause mammalian toxicity. We evaluated the reproductive toxicity of acetamiprid in adult male Sprague Dawley rats. Rats were given oral acetamiprid alone or with vitamin E for 35 days. Rat plasma testosterone concentration and sperm quality decreased significantly as the levels of luteinizing hormone (LH) increased after exposure. At the same time, acetamiprid increased malondialdehyde and nitric oxide (NO) levels of Leydig cells...
January 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28387563/curcumin-upregulates-antioxidant-defense-lon-protease-and-heat-shock-protein-70-under-hyperglycemic-conditions-in-human-hepatoma-cells
#20
Shivona Gounden, Anil Chuturgoon
Sirtuin 3 (SIRT3) regulates mitochondrial antioxidant (AO) defense and improves mitochondrial disorders. Curcumin protects mitochondria; however, the mechanisms need investigation. We postulated that curcumin increases AO defense under hyperglycemic conditions in HepG2 cells through SIRT3-mediated mechanisms. Cell viability was determined in HepG2 cells cultured with 5 mM glucose, 19.9 mM mannitol, vehicle control, 10 mM glucose, and 30 mM glucose in the absence or presence of curcumin for 24 h. SIRT3, nuclear factor-kappa B (NF-κB), heat-shock protein 70 (Hsp70), and Lon protein expressions were determined using western blot...
May 2017: Journal of Medicinal Food
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