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https://www.readbyqxmd.com/read/28747539/steroidogenesis-in-leydig-cells-effects-of-aging-and-environmental-factors
#1
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
#2
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
#3
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...
June 28, 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
#4
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
#5
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
#6
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...
May 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28501614/shaping-mitochondrial-dynamics-the-role-of-camp-signalling
#7
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
#8
Pablo S Villar, Ricardo Delgado, Cecilia Vergara, Juan G Reyes, Juan Bacigalupo
The mechanisms that power the physiological events occuring in cilia, flagella and microvilli are of fundamental importance for the functions of these important and ubicuous organelles. The olfactory epithelium (OE) 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 approximately 50 x 0.2 μm, devoid of inner membranes embedded in a mucus layer...
May 12, 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
#9
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
#10
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...
May 4, 2017: Gene
https://www.readbyqxmd.com/read/28463107/pde2a2-regulates-mitochondria-morphology-and-apoptotic-cell-death-via-local-modulation-of-camp-pka-signalling
#11
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
#12
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
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/28351484/hypocapnic-hypothesis-of-leigh-disease
#16
Ewa Pronicka
Leigh syndrome (LS) is a neurogenetic disorder of children caused by mutations in at least 75 genes which impair mitochondrial bioenergetics. The changes have typical localization in basal ganglia and brainstem, and typical histological picture of spongiform appearance, vascular proliferation and gliosis. ATP deprivation, free radicals and lactate accumulation are suspected to be the causes. Hypocapnic hypothesis proposed in the paper questions the energy deprivation as the mechanism of LS. We assume that the primary harmful factor is hypocapnia (decrease in pCO2) and respiratory alkalosis (increase in pH) due to hyperventilation, permanent or in response to stress...
April 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28336949/induction-of-apoptosis-and-ganoderic-acid-biosynthesis-by-camp-signaling-in-ganoderma-lucidum
#17
Bang-Jau You, Ni Tien, Miin-Huey Lee, Bo-Ying Bao, Yih-Shyuan Wu, Tsung-Chi Hu, Hong-Zin Lee
Apoptosis is an essential physiological process that controls many important biological functions. However, apoptosis signaling in relation to secondary metabolite biosynthesis in plants and fungi remains a mystery. The fungus Ganoderma lucidum is a popular herbal medicine worldwide, but the biosynthetic regulation of its active ingredients (ganoderic acids, GAs) is poorly understood. We investigated the role of 3',5'-cyclic adenosine monophosphate (cAMP) signaling in fungal apoptosis and GA biosynthesis in G...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28254846/rhoa-inhibits-the-hypoxia-induced-apoptosis-and-mitochondrial-dysfunction-in-chondrocytes-via-positively-regulating-the-creb-phosphorylation
#18
Kai Zhang, Dianming Jiang
Chondrocytes that are embedded within the growth plate or the intervertebral disc are sensitive to environmental stresses, such as inflammation and hypoxia. However, little is known about the molecular signalling pathways underlining the hypoxia-induced mitochondrial dysfunction and apoptosis in chondrocytes. In the present study, we firstly examined the hypoxia-induced apoptosis, mitochondrial dysfunction and the activation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) signalling in human chondrocyte cell line, C28/I2 and then investigated the regulatory role of RhoA, a well-recognized apoptosis suppressor, in such process, with gain-of-function strategy...
April 30, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28202681/components-of-the-mitochondrial-camp-signalosome
#19
REVIEW
Stefania Monterisi, Manuela Zaccolo
3'-5'-Cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) signalling is activated by different extracellular stimuli and mediates many diverse processes within the same cell. It is now well established that in order to translate into the appropriate cellular function multiple extracellular inputs, which may act simultaneously on the same cell, the cAMP/PKA signalling pathway is compartmentalised. Multimolecular complexes are organised at specific subcellular sites to generate spatially confined signalosomes, which include effectors, modulators and targets of the pathway...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28096195/multifunctional-mitochondrial-epac1-controls-myocardial-cell-death
#20
Loubina Fazal, Marion Laudette, Sílvia Paula-Gomes, Sandrine Pons, Caroline Conte, Florence Tortosa, Pierre Sicard, Yannis Sainte-Marie, Malik Bisserier, Olivier Lairez, Alexandre Lucas, Jérôme Roy, Bijan Ghaleh, Jérémy Fauconnier, Jeanne Mialet-Perez, Frank Lezoualc'h
RATIONALE: Although the second messenger cyclic AMP (cAMP) is physiologically beneficial in the heart, it largely contributes to cardiac disease progression when dysregulated. Current evidence suggests that cAMP is produced within mitochondria. However, mitochondrial cAMP signaling and its involvement in cardiac pathophysiology are far from being understood. OBJECTIVE: To investigate the role of MitEpac1 (mitochondrial exchange protein directly activated by cAMP 1) in ischemia/reperfusion injury...
February 17, 2017: Circulation Research
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