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https://www.readbyqxmd.com/read/28292875/in-vivo-ca-2-dynamics-induced-by-ca-2-injection-in-individual-rat-skeletal-muscle-fibers
#1
Mario Wakizaka, Hiroaki Eshima, Yoshinori Tanaka, Hideki Shirakawa, David C Poole, Yutaka Kano
In contrast to cardiomyocytes, store overload-induced calcium ion (Ca(2+)) release (SOICR) is not considered to constitute a primary Ca(2+) releasing system from the sarcoplasmic reticulum (SR) in skeletal muscle myocytes. In the latter, voltage-induced Ca(2+) release (VICR) is regarded as the dominant mechanism facilitating contractions. Any role of the SOICR in the regulation of cytoplasmic Ca(2+) concentration ([Ca(2+)]i) and its dynamics in skeletal muscle in vivo remains poorly understood. By means of in vivo single fiber Ca(2+) microinjections combined with bioimaging techniques, we tested the hypothesis that the [Ca(2+)]i dynamics following Ca(2+) injection would be amplified and fiber contraction facilitated by SOICR...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28290590/the-ca-2-atpase-pump-facilitates-bidirectional-proton-transport-across-the-sarco-endoplasmic-reticulum
#2
L Michel Espinoza-Fonseca
Ca(2+) transport across the sarco/endoplasmic reticulum (SR) plays an essential role in intracellular Ca(2+) homeostasis, signalling, cell differentiation and muscle contractility. During SR Ca(2+) uptake and release, proton fluxes are required to balance the charge deficit generated by the exchange of Ca(2+) and other ions across the SR. During Ca(2+) uptake by the SR Ca(2+)-ATPase (SERCA), two protons are countertransported from the SR lumen to the cytosol, thus partially compensating for the charge moved by Ca(2+) transport...
March 14, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28287621/restoring-the-impaired-cardiac-calcium-homeostasis-and-cardiac-function-in-iron-overload-rats-by-the-combined-deferiprone-and-n-acetyl-cysteine
#3
Suwakon Wongjaikam, Sirinart Kumfu, Juthamas Khamseekaew, Siriporn C Chattipakorn, Nipon Chattipakorn
Intracellular calcium [Ca(2+)]i dysregulation plays an important role in the pathophysiology of iron overload cardiomyopathy. Although either iron chelators or antioxidants provide cardioprotection, a comparison of the efficacy of deferoxamine (DFO), deferiprone (DFP), deferasirox (DFX), N-acetyl cysteine (NAC) or a combination of DFP plus NAC on cardiac [Ca(2+)]i homeostasis in chronic iron overload has never been investigated. Male Wistar rats were fed with either a normal diet or a high iron (HFe) diet for 4 months...
March 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28278204/sarcolipin-deletion-exacerbates-soleus-muscle-atrophy-and-weakness-in-phospholamban-overexpressing-mice
#4
Val A Fajardo, Daniel Gamu, Andrew Mitchell, Darin Bloemberg, Eric Bombardier, Paige J Chambers, Catherine Bellissimo, Joe Quadrilatero, A Russell Tupling
Sarcolipin (SLN) and phospholamban (PLN) are two small proteins that regulate the sarco(endo)plasmic reticulum Ca2+-ATPase pumps. In a recent study, we discovered that Pln overexpression (PlnOE) in slow-twitch type I skeletal muscle fibers drastically impaired SERCA function and caused a centronuclear myopathy-like phenotype, severe muscle atrophy and weakness, and an 8 to 9-fold upregulation of SLN protein in the soleus muscles. Here, we sought to determine the physiological role of SLN upregulation, and based on its role as a SERCA inhibitor, we hypothesized that it would represent a maladaptive response that contributes to the SERCA dysfunction and the overall myopathy observed in the PlnOE mice...
2017: PloS One
https://www.readbyqxmd.com/read/28275147/localization-and-characterization-of-cyp76ae2-part-of-thapsigargin-biosynthesis-in-thapsia-garganica
#5
Trine Bundgaard Andersen, Karen Agatha Martinez-Swatson, Silas Anselm Rasmussen, Berin Alain Boughton, Kirsten Jørgensen, Johan Andersen-Ranberg, Nils Nyberg, Søren Brøgger Christensen, Henrik Toft Simonsen
The Mediterranean plant Thapsia garganica (dicot, Apiaceae), also known as Deadly carrot, produces the highly toxic compound thapsigargin. This compound is a potent inhibitor of the SERCA calcium pump in mammals, and is of industrial importance as the active moiety of the anticancer drug Mipsagargin, currently in clinical trials. Knowledge of thapsigargin in planta storage and biosynthesis has so far been limited. Here we present the putative second step in thapsigargin biosynthesis, by showing that the cytochrome P450 TgCYP76AE2, transiently expressed in Nicotiana benthamiana, converts epikunzeaol into epidihydrocostunolide...
March 8, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28261092/screening-for-small-molecule-inhibitors-of-statin-induced-app-c-terminal-toxic-fragment-production
#6
Karen S Poksay, Douglas J Sheffler, Patricia Spilman, Jesus Campagna, Barbara Jagodzinska, Olivier Descamps, Olivia Gorostiza, Alex Matalis, Michael Mullenix, Dale E Bredesen, Nicholas D P Cosford, Varghese John
Alzheimer's disease (AD) is characterized by neuronal and synaptic loss. One process that could contribute to this loss is the intracellular caspase cleavage of the amyloid precursor protein (APP) resulting in release of the toxic C-terminal 31-amino acid peptide APP-C31 along with the production of APPΔC31, full-length APP minus the C-terminal 31 amino acids. We previously found that a mutation in APP that prevents this caspase cleavage ameliorated synaptic loss and cognitive impairment in a murine AD model...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28254579/resveratrol-induced-autophagy-is-dependent-on-ip3rs-and-on-cytosolic-ca-2
#7
Tomas Luyten, Kirsten Welkenhuyzen, Gemma Roest, Elzbieta Kania, Liwei Wang, Mart Bittremieux, David I Yule, Jan B Parys, Geert Bultynck
Previous work revealed that intracellular Ca(2+) signals and the inositol 1,4,5-trisphosphate (IP3) receptors (IP3R) are essential to increase autophagic flux in response to mTOR inhibition, induced by either nutrient starvation or rapamycin treatment. Here, we investigated whether autophagy induced by resveratrol, a polyphenolic phytochemical reported to trigger autophagy in a non-canonical way, also requires IP3Rs and Ca(2+) signaling. Resveratrol augmented autophagic flux in a time-dependent manner in HeLa cells...
February 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28249687/activation-of-endoplasmic-reticulum-calcium-leak-by-2-apb-depends-on-the-luminal-calcium-concentration
#8
Daniel Leon-Aparicio, Jesus Chavez-Reyes, Agustin Guerrero-Hernandez
It has been shown that 2-APB is a nonspecific modulator of ion channel activity, while most of the channels are inhibited by this compound, there are few examples of channels that are activated by 2-APB. Additionally, it has been shown that, 2-APB leads to a reduction in the luminal endoplasmic reticulum Ca(2+) level ([Ca(2+)]ER) and we have carried out simultaneous recordings of both [Ca(2+)]i and the [Ca(2+)]ER in HeLa cell suspensions to assess the mechanism involved in this effect. This approach allowed us to determine that 2-APB induces a reduction in the [Ca(2+)]ER by activating an ER-resident Ca(2+) permeable channel more than by inhibiting the activity of SERCA pumps...
February 8, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28237334/functional-involvement-of-protein-kinase-c-rho-kinase-and-trpc3-decreases-while-plc-increases-with-advancement-of-pregnancy-in-mediating-oxytocin-induced-myometrial-contractions-in-water-buffaloes-bubalus-bubalis
#9
Abhishek Sharma, Udayraj P Nakade, Soumen Choudhury, Satish Kumar Garg
Present study unravels the involvement of different calcium signaling pathways in oxytocin-induced contractions in myometrium of non-pregnant and pregnant buffaloes during early and mid-pregnancy stages. Uteri of pregnant animals were more sensitive than of non-pregnant buffaloes. Phasic contractions and frequency of contraction significantly increased with advancement of pregnancy, while tonic contractions non-significantly and amplitude significantly decreased from six months pregnancy onward. Oxytocin produced concentration-dependent-contraction on isolated myometrial strips of pregnant and non-pregnant buffaloes and the dose response curves (DRCs) of oxytocin were significantly (P < 0...
April 1, 2017: Theriogenology
https://www.readbyqxmd.com/read/28223472/overexpression-of-sarcoendoplasmic-reticulum-calcium-atpase-2a-promotes-cardiac-sympathetic-neurotransmission-via-abnormal-endoplasmic-reticulum-and-mitochondria-ca-2-regulation
#10
Julia Shanks, Neil Herring, Errin Johnson, Kun Liu, Dan Li, David J Paterson
Reduced cardiomyocyte excitation-contraction coupling and downregulation of the SERCA2a (sarcoendoplasmic reticulum calcium ATPase 2a) is associated with heart failure. This has led to viral transgene upregulation of SERCA2a in cardiomyocytes as a treatment. We hypothesized that SERCA2a gene therapy expressed under a similar promiscuous cytomegalovirus promoter could also affect the cardiac sympathetic neural axis and promote sympathoexcitation. Stellate neurons were isolated from 90 to 120 g male, Sprague-Dawley, Wistar Kyoto, and spontaneously hypertensive rats...
April 2017: Hypertension
https://www.readbyqxmd.com/read/28213819/conditional-knockout-of-activin-like-kinase-1-alk-1-leads-to-heart-failure-without-maladaptive-remodeling
#11
Kevin J Morine, Xiaoying Qiao, Vikram Paruchuri, Mark J Aronovitz, Emily E Mackey, Lyanne Buiten, Jonathan Levine, Keshan Ughreja, Prerna Nepali, Robert M Blanton, Richard H Karas, S Paul Oh, Navin K Kapur
Activin like kinase-1 (AlK-1) mediates signaling via the transforming growth factor beta (TGFβ) family of ligands. AlK-1 activity promotes endothelial proliferation and migration. Reduced AlK-1 activity is associated with arteriovenous malformations. No studies have examined the effect of global AlK-1 deletion on indices of cardiac remodeling. We hypothesized that reduced levels of AlK-1 promote maladaptive cardiac remodeling. To test this hypothesis, we employed AlK-1 conditional knockout mice (cKO) harboring the ROSA26-CreER knock-in allele, whereby a single dose of intraperitoneal tamoxifen triggered ubiquitous Cre recombinase-mediated excision of floxed AlK-1 alleles...
February 17, 2017: Heart and Vessels
https://www.readbyqxmd.com/read/28212796/sodium-calcium-exchanger-in-pig-coronary-artery
#12
A K Grover
This review focuses on the sodium-calcium exchangers (NCX) in the left anterior descending coronary artery smooth muscle. Bathing tissues in Na(+)-substituted solutions caused them to contract. In cultured smooth muscle cells, it increased the cytosolic Ca(2+) concentration and extracellular entry of (45)Ca(2+). All three activities were attributed to NCX since they were inhibited by NCX inhibitors. The tissues also expressed the sarco/endoplasmic reticulum (SER) Ca(2+) pump SERCA2b whose activity was much greater than that of NCX...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28196740/dpb162-ae-an-inhibitor-of-store-operated-ca-2-entry-can-deplete-the-endoplasmic-reticulum-ca-2-store
#13
Mart Bittremieux, Julia V Gerasimenko, Marleen Schuermans, Tomas Luyten, Eloise Stapleton, Kamil J Alzayady, Humbert De Smedt, David I Yule, Katsuhiko Mikoshiba, Peter Vangheluwe, Oleg V Gerasimenko, Jan B Parys, Geert Bultynck
Store-operated Ca(2+) entry (SOCE), an important Ca(2+) signaling pathway in non-excitable cells, regulates a variety of cellular functions. To study its physiological role, pharmacological tools, like 2-aminoethyl diphenylborinate (2-APB), are used to impact SOCE. 2-APB is one of the best characterized SOCE inhibitors. However, 2-APB also activates SOCE at lower concentrations, while it inhibits inositol 1,4,5-trisphosphate receptors (IP3Rs), sarco/endoplasmic reticulum Ca(2+)-ATPases (SERCAs) and other ion channels, like TRP channels...
February 1, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28188731/design-in-silico-and-in%C3%A2-vitro-evaluation-of-curcumin-analogues-against-plasmodium-falciparum
#14
Chandrajit Dohutia, Dipak Chetia, Kabita Gogoi, Kishore Sarma
The polyphenolic compound curcumin has been reported for its antimalarial properties in various scientific studies. Plasmodium falciparum ATP6, the parasite orthologue of mammalian sarcoplasmic Ca(2+) ATPase (SERCA) has been identified as a key molecular target of both artemisinin and curcumin. The work was thereby undertaken to study the anti-malarial properties of two different series of curcumin analogues based on their docking interactions with PfATP6 and correlating the results with their anti-malarial activity...
April 2017: Experimental Parasitology
https://www.readbyqxmd.com/read/28183802/differential-effects-of-anoctamins-on-intracellular-calcium-signals
#15
Inês Cabrita, Roberta Benedetto, Ana Fonseca, Podchanart Wanitchakool, Lalida Sirianant, Boris V Skryabin, Laura K Schenk, Hermann Pavenstädt, Rainer Schreiber, Karl Kunzelmann
The Ca(2+) activated Cl(-) channel TMEM16A [anoctamin (ANO)1] is homologous to yeast Ist2 and has been shown to tether the cortical endoplasmic reticulum (ER) to the plasma membrane. We therefore examined whether ANO1 and other members of the ANO family affect intracellular Ca(2+) ([Ca(2+)]i) signals. It is shown that expression of ANO1 augments Ca(2+) store release upon stimulation of GPCRs, whereas knockdown of ANO1, or lack of Ano1 expression in Ano1(-/-) animals as shown in an earlier report, inhibits Ca(2+) release...
February 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28179072/orai3-channel-is-the-2-apb-induced-endoplasmic-reticulum-calcium-leak
#16
Daniel Leon-Aparicio, Jonathan Pacheco, Jesus Chavez-Reyes, Jose M Galindo, Jesus Valdes, Luis Vaca, Agustin Guerrero-Hernandez
We have studied in HeLa cells the molecular nature of the 2-APB induced ER Ca(2+) leak using synthetic Ca(2+) indicators that report changes in both the cytoplasmic ([Ca(2+)]i) and the luminal ER ([Ca(2+)]ER) Ca(2+) concentrations. We have tested the hypothesis that Orai channels participate in the 2-APB-induced ER Ca(2+) leak that was characterized in the companion paper. The expression of the dominant negative Orai1 E106A mutant, which has been reported to block the activity of all three types of Orai channels, inhibited the effect of 2-APB on the [Ca(2+)]ER but did not decrease the ER Ca(2+) leak after thapsigargin (TG)...
January 23, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28169003/increased-calcium-leak-associated-with-reduced-calsequestrin-expression-in-hyperthyroid-cardiomyocytes
#17
David R de Alba-Aguayo, Natalia Pavón, Martha Mercado-Morales, Miyamin Miranda-Saturnino, Mavil López-Casamichana, Agustin Guerrero-Hernández, Angelica Rueda
INTRODUCTION: Calcium (Ca(2+)) leak during cardiac diastole is chiefly mediated by intracellular Ca(2+) channel/Ryanodine Receptors. Increased diastolic Ca(2+) leak has been proposed as the mechanism underlying the appearance of hereditary arrhythmias. However, little is known about alterations in diastolic Ca(2+) leak and the specific roles played by key intracellular Ca(2+)-handling proteins in hyperthyroidism, a known arrhythmogenic condition. AIM: We sought to determine whether there were modifications in diastolic Ca(2+) leak, based on the recording of Ca(2+) sparks and Ca(2+) waves; we also investigated changes in the expression and activity of key Ca(2+) handling proteins, including ryanodine receptors, Sarco-Endoplasmic Reticulum Ca(2+) ATPase pump and calsequestrin in isolated left-ventricular cardiomyocytes isolated from hyperthyroid rats...
January 23, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28150875/atp2a3-gene-as-an-important-player-for-resveratrol-anticancer-activity-in-breast-cancer-cells
#18
Eduardo Izquierdo-Torres, Gabriela Rodríguez, Iván Meneses-Morales, Angel Zarain-Herzberg
The Ca(2+) -ATPases from the Sarco/endoplasmic reticulum (SERCA) are fundamental for maintaining intracellular [Ca(2+) ] homeostasis by pumping Ca(2+) into the endoplasmic reticulum (ER) of eukaryotic cells. SERCA enzymes are encoded by three different genes (ATP2A1-3), whose expression occurs in a tissue and development stage-specific manner. It has been reported alterations in the expression of SERCA2 and SERCA3 pumps in different types of cancer: oral, lung, colon, stomach, central nervous system, thyroid, breast, and prostate...
February 2, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28143888/divergent-mechanisms-leading-to-signaling-dysfunction-in-embryonic-muscle-by-bisphenol-a-and-tetrabromobisphenol-a
#19
Rui Zhang, Isaac N Pessah
Bisphenol A (BPA) and its brominated derivative tetrabromobisphenol A (TBBPA) are high production volume chemicals used in the manufacture of various consumer products. Although regarded as endocrine disruptors, these chemicals are suspected to exert nongenomic actions on muscle function that are not well understood. Using skeletal muscle microsomes, we examined the effects of BPA and TBBPA on ryanodine receptor type 1 (RyR1), dihydropyridine receptor (DHPR), and sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase (SERCA)...
April 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28143473/chemical-composition-vasorelaxant-antioxidant-and-antiplatelet-effects-of-essential-oil-of-artemisia-campestris-l-from-oriental-morocco
#20
Ikram Dib, Marie-Laure Fauconnier, Marianne Sindic, Fatima Belmekki, Asmae Assaidi, Mohamed Berrabah, Hassane Mekhfi, Mohammed Aziz, Abdelkhaleq Legssyer, Mohamed Bnouham, Abderrahim Ziyyat
BACKGROUND: Artemisia campestris L. (Asteraceae) is a medicinal herb traditionally used to treat hypertension and many other diseases. Hence, this study is aimed to analyze the essential oil of A. campestris L (AcEO) and to investigate the antiplatelet, antioxidant effects and the mechanisms of its vasorelaxant effect. METHODS: The chemical composition of AcEO was elucidated using GC/MS analysis. Then, the antioxidant effect was tested on DPPH radical scavenging and on the prevention of β-carotene bleaching...
January 31, 2017: BMC Complementary and Alternative Medicine
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