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Mitochondria cAMP

Francesco Bellomo, Anna Signorile, Grazia Tamma, Marianna Ranieri, Francesco Emma, Domenico De Rasmo
Nephropathic cystinosis (NC) is a rare disease caused by mutations in the CTNS gene encoding for cystinosin, a lysosomal transmembrane cystine/H+ symporter, which promotes the efflux of cystine from lysosomes to cytosol. NC is the most frequent cause of Fanconi syndrome (FS) in young children, the molecular basis of which is not well established. Proximal tubular cells have very high metabolic rate due to the active transport of many solutes. Not surprisingly, mitochondrial disorders are often characterized by FS...
March 16, 2018: Cellular and Molecular Life Sciences: CMLS
Jérôme Salignon, Magali Richard, Etienne Fulcrand, Hélène Duplus-Bottin, Gaël Yvert
Living systems control cell growth dynamically by processing information from their environment. Although responses to a single environmental change have been intensively studied, little is known about how cells react to fluctuating conditions. Here, we address this question at the genomic scale by measuring the relative proliferation rate (fitness) of 3,568 yeast gene deletion mutants in out-of-equilibrium conditions: periodic oscillations between two environmental conditions. In periodic salt stress, fitness and its genetic variance largely depended on the oscillating period...
March 5, 2018: Molecular Systems Biology
Jiaqi Gu, Lingchun Luo, Qian Wang, Songfan Yan, Jing Lin, Dan Li, Bingbing Cao, Hongxia Mei, Binyu Ying, Lu Bin, Fang Gao Smith, Sheng-Wei Jin
Inflammation always accompanies infection during sepsis. Mitochondrial dysfunction and the role of reactive oxygen species (ROS) produced by mitochondria have been proposed in the pathogenesis of sepsis. Maresins have protective and resolving effects in experimental models of infection. In the present study, we investigated the effects of maresin 1 (MaR1) on mitochondrial function in cecal ligation and puncture (CLP)-induced sepsis and sepsis patients to identify mechanisms underlying maresin 1-mediated stimulation of ROS in mitochondria...
February 21, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Jinjiang Fan, Kevin Wang, Barry Zirkin, Vassilios Papadopoulos
The outer mitochondrial membrane translocator protein (TSPO) binds cholesterol with high affinity and is involved in mediating its delivery into mitochondria, the rate-limiting step in hormone-induced steroidogenesis. Specific ligand binding to TSPO has been shown to initiate steroid formation. However, recent studies of the genetic deletion of Tspo have provided conflicting results. Here we address and extend previous studies by examining the effects of Tspo - specific mutations on steroid formation in the hormone- and cAMP-responsive MA-10 cells, using the CRISPR/Cas9 system...
December 28, 2017: Endocrinology
Guanglei Chang, Jian Liu, Shu Qin, Youqin Jiang, Peng Zhang, Hui Yu, Kai Lu, Nan Zhang, Li Cao, Ying Wang, Yong Li, Dongying Zhang
Accumulating evidence suggests that glucagon-like peptide-1 (GLP-1) and its analogues exert cardioprotective effects via modulating cardiomyocyte metabolism. Mitochondria play a pivotal role in the regulation of cell metabolism. It was hypothesized that treatment with exenatide, a GLP-1 analogue, may exert cardioprotective effects by improving mitochondrial function in an in vitro model of hypoxia/reoxygenation (H/R). H9c2 cells were employed to establish an in vitro model of H/R. Exenatide was added to the cells for 30 min prior to exposure to hypoxia...
December 12, 2017: International Journal of Molecular Medicine
Hao Ding, Feng Bai, Hongdi Cao, Jing Xu, Li Fang, Jining Wu, Qi Yuan, Yang Zhou, Qi Sun, Weichun He, Chunsun Dai, Ke Zen, Lei Jiang, Junwei Yang
AIMS: Cyclic adenosine 3'5'-monophosphate (cAMP) is a universal second messenger that plays an important role in intracellular signal transduction. cAMP is synthesized by adenylate cyclases from adenosine triphosphate and terminated by the phosphodiesterases (PDEs). In the present study, we investigated the role of the cAMP pathway in tubular epithelial cell mitochondrial biogenesis in the pathogenesis of renal fibrosis. RESULTS: We found that the cAMP levels were decreased in fibrotic kidney tissues, and replenishing cAMP could ameliorate tubular atrophy and extracellular matrix deposition...
February 22, 2018: Antioxidants & Redox Signaling
Jinwoo Lee, Colin Jefcoate
Recent advances in fluorescence microscopy, coupled with CRISPR/Cas9 gene editing technology, provide opportunities for understanding gene regulation at the single-cell level. The application of direct imaging shown here provides an in situ side-by-side comparison of CRISPR/Cas9-edited cells and adjacent unedited cells. We apply this methodology to the steroidogenic acute regulatory protein (StAR) gene in Y-1 adrenal cells and MA-10 testis cells. StAR is a gatekeeper protein that controls the access of cholesterol from the cytoplasm to the inner mitochondria...
2017: Frontiers in Endocrinology
Alexander M Firsov, Irina G Rybalkina, Elena A Kotova, Tatyana I Rokitskaya, Vadim N Tashlitsky, Galina A Korshunova, Sergei D Rybalkin, Yuri N Antonenko
The present study demonstrated for the first time the interaction between adenosine 3',5'-cyclic monophosphate (cAMP), one of the most important signaling compounds in living organisms, and the mitochondria-targeted antioxidant plastoquinonyl-decyltriphenylphosphonium (SkQ1). The data obtained on model liquid membranes and human platelets revealed the ability of SkQ1 to selectively transport cAMP, but not guanosine 3',5'-cyclic monophosphate (cGMP), across both artificial and natural membranes. In particular, SkQ1 elicited translocation of cAMP from the source to the receiving phase of a Pressman-type cell, while showing low activity with cGMP...
February 2018: Biochimica et Biophysica Acta
Fubiao Shi, Sheila Collins
β-adrenergic receptors (βARs) are well established for conveying the signal from catecholamines to adipocytes. Acting through the second messenger cyclic adenosine monophosphate (cAMP) they stimulate lipolysis and also increase the activity of brown adipocytes and the 'browning' of adipocytes within white fat depots (so-called 'brite' or 'beige' adipocytes). Brown adipose tissue mitochondria are enriched with uncoupling protein 1 (UCP1), which is a regulated proton channel that allows the dissipation of chemical energy in the form of heat...
September 26, 2017: Hormone Molecular Biology and Clinical Investigation
Shengnan Wu, Qiulun Lu, Qilong Wang, Ye Ding, Zejun Ma, Xiaoxiang Mao, Kai Huang, Zhonglin Xie, Ming-Hui Zou
BACKGROUND: FUN14 domain containing 1 (FUNDC1) is a highly conserved outer mitochondrial membrane protein. The aim of this study is to examine whether FUNDC1 modulates the mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs), mitochondrial morphology, and function in cardiomyocytes and intact hearts. METHODS: The impacts of FUNDC1 on MAMs formation and cardiac functions were studied in mouse neonatal cardiomyocytes, in mice with cardiomyocyte-specific Fundc1 gene knockout ( Fundc1 f/Y /Cre αMyHC+/- ), and in the cardiac tissues of the patients with heart failure...
December 5, 2017: Circulation
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...
December 2017: Journal of Leukocyte Biology
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 children and 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...
December 2017: Gastroenterology
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 have 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 knockout fibroblasts have a defect in OXPHOS activity and attempt to compensate for this defect by increasing OXPHOS proteins...
November 1, 2017: Journal of Cell Science
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
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
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
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
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
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
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
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