keyword
MENU ▼
Read by QxMD icon Read
search

KN-93

keyword
https://www.readbyqxmd.com/read/29129208/augmented-gene-expression-triggered-by-na-k-atpase-inhibition-role-of-ca-2-i-mediated-and-independent-excitation-transcription-coupling
#1
Larisa V Smolyaninova, Svetlana V Koltsova, Svetlana V Sidorenko, Sergei N Orlov
In rat vascular smooth muscle cells (RVSMC), 3-h Na(+),K(+)-ATPase inhibition by ouabain or in K(+)-free medium resulted in the inversion of the [Na(+)]i/[K(+)]i ratio and elevation up to 7-fold the content of Egr1, Atf3, Nr4a1 and Ptgs2 mRNAs. Ouabain increased the rate of 45Ca(2+) influx by 2-fold that was abolished by L-type voltage-gated Ca(2+) channel blocker nicardipine, but it was resistant to Na(+)/Ca(2+) exchanger inhibitor KB-R7943. To study the role of Ca(2+)-mediated signaling in the expression of Na(+)i/K(+)i-sensitive genes we used intracellular Ca(2+) chelator BAPTA and incubated RVSMC in Ca(2+)-free medium...
December 2017: Cell Calcium
https://www.readbyqxmd.com/read/29034548/electroacupuncture-alleviates-chemotherapy-induced-pain-through-inhibiting-phosphorylation-of-spinal-camkii-in-rats
#2
Y Zhang, A Li, J Xin, K Ren, B M Berman, L Lao, R-X Zhang
BACKGROUND: Current medical treatments for chemotherapy-induced pain (CIP) are either ineffective or have adverse side effects. Acupuncture may alleviate CIP, but its effectiveness against this condition has not been studied. Paclitaxel causes neuropathic pain in cancer patients. METHODS: We evaluated the effects of electroacupuncture (EA) on paclitaxel-induced CIP in a rat model. Paclitaxel (2 mg/kg) or vehicle was injected (i.p.) on alternate days of 0-6. The resulting pain was treated with 10 Hz/2 mA/0...
October 16, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28971270/calcium-calmodulin-dependent-protein-kinase-iv-camkiv-mediates-acute-skeletal-muscle-inflammatory-response
#3
DanDan Shi, RuiCai Gu, YaFeng Song, MaoChao Ding, Tao Huang, MengXia Guo, JiangWei Xiao, WenHua Huang, Hua Liao
The objective of this study is to investigate the role of Calmodulin-dependent protein kinase IV (CaMKIV) in Cardiotoxin (CTX)-induced mice muscle inflammation. CTX injection i.m. was performed to induce B6 mice acute tibialis anterior (TA) muscle injury. The mice were then injected i.p. with the recombinant CaMKIV protein or its antagonist KN-93. Immunoblotting was used to assess Calmodulin (CaM) and CaMKIV levels. Immunofluorescence was used to detect intramuscular infiltration or major histocompatibility complex (MHC)-I expression in damaged muscle...
October 2, 2017: Inflammation
https://www.readbyqxmd.com/read/28912066/the-camp-effectors-pka-and-epac-activate-endothelial-no-synthase-through-pi3k-akt-pathway-in-human-endothelial-cells
#4
Verónica García-Morales, María Luaces-Regueira, Manuel Campos-Toimil
3',5'-Cyclic adenosine monophosphate (cAMP) exerts an endothelium-dependent vasorelaxant action by stimulating endothelial NO synthase (eNOS) activity, and the subsequent NO release, through cAMP protein kinase (PKA) and exchange protein directly activated by cAMP (Epac) activation in endothelial cells. Here, we have investigated the mechanism by which the cAMP-Epac/PKA pathway activates eNOS. cAMP-elevating agents (forskolin and dibutyryl-cAMP) and the joint activation of PKA (6-Bnz-cAMP) and Epac (8-pCPT-2'-O-Me-cAMP) increased cytoplasmic Ca(2+) concentration ([Ca(2+)]c) in ≤30% of fura-2-loaded isolated human umbilical vein endothelial cells (HUVEC)...
September 11, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28867536/nitric-oxide-and-camkii-critical-steps-in-the-cardiac-contractile-response-to-igf-1-and-swim-training
#5
Juan I Burgos, Alejandra M Yeves, Jorge P Barrena, Enrique L Portiansky, Martín G Vila-Petroff, Irene L Ennis
Cardiac adaptation to endurance training includes improved contractility by a non-yet clarified mechanism. Since IGF-1 is the main mediator of the physiological response to exercise, we explored its effect on cardiac contractility and the putative involvement of nitric oxide (NO) and CaMKII in control and swim-trained mice. IGF-1 increased cardiomyocyte shortening (128.1±4.6% vs. basal; p˂0.05) and accelerated relaxation (time to 50% relengthening: 49.2±2.0% vs. basal; p˂0.05), effects abrogated by inhibition of: AKT with MK-2206, NO production with the NO synthase (NOS) inhibitor L-NAME and the specific NOS1 inhibitor nitroguanidine (NG), and CaMKII with KN-93...
September 1, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28859293/impaired-calcium-homeostasis-is-associated-with-sudden-cardiac-death-and-arrhythmias-in-a-genetic-equivalent-mouse-model-of-the-human-hrc-ser96ala-variant
#6
Christos Tzimas, Daniel M Johnson, Demetrio J Santiago, Elizabeth Vafiadaki, Demetrios A Arvanitis, Constantinos H Davos, Aimilia Varela, Nikolaos C Athanasiadis, Constantinos Dimitriou, Michalis Katsimpoulas, Stephan Sonntag, Mariya Kryzhanovska, Doron Shmerling, Stephan E Lehnart, Karin R Sipido, Evangelia G Kranias, Despina Sanoudou
Aims: The histidine-rich calcium-binding protein (HRC) Ser96Ala variant has previously been identified as a potential biomarker for ventricular arrhythmias and sudden cardiac death in patients with idiopathic dilated cardiomyopathy. Herein, the role of this variant in cardiac pathophysiology is delineated through a novel mouse model, carrying the human mutation in the homologous mouse position. Methods and results: The mouse HRC serine 81, homologous to human HRC serine 96, was mutated to alanine, using knock-in gene targeting...
September 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28836001/the-reduced-myofilament-responsiveness-to-calcium-contributes-to-the-negative-force-frequency-relationship-in-rat-cardiomyocytes-role-of-reactive-oxygen-species-and-p-38-map-kinase
#7
María Sofía Espejo, Ignacio Aiello, Marisa Sepúlveda, Martín G Vila Petroff, Ernesto A Aiello, Verónica C De Giusti
The force-frequency relationship (FFR) is an important intrinsic regulatory mechanism of cardiac contractility. However, a decrease (negative FFR) or no effect (flat FFR) on contractile force in response to an elevation of heart rate is present in the normal rat or in human heart failure. Reactive oxygen species (ROS) can act as intracellular signaling molecules activating diverse kinases as calcium-calmodulin-dependent protein kinase II (CaMKII) and p-38 MAP kinase (p-38K). Our aim was to elucidate the intracellular molecules implicated in the FFR of isolated rat ventricular myocytes...
August 23, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28792844/trpa1-ion-channel-stimulation-enhances-cardiomyocyte-contractile-function-via-a-camkii-dependent-pathway
#8
Spencer R Andrei, Monica Ghosh, Pritam Sinharoy, Souvik Dey, Ian N Bratz, Derek S Damron
RATIONALE: Transient receptor potential channels of the ankyrin subtype-1 (TRPA1) are non-selective cation channels that show high permeability to calcium. Previous studies from our laboratory have demonstrated that TRPA1 ion channels are expressed in adult mouse ventricular cardiomyocytes (CMs) and are localized at the z-disk, costamere and intercalated disk. The functional significance of TRPA1 ion channels in the modulation of CM contractile function have not been explored. OBJECTIVE: To identify the extent to which TRPA1 ion channels are involved in modulating CM contractile function and elucidate the cellular mechanism of action...
August 9, 2017: Channels
https://www.readbyqxmd.com/read/28754591/camkii-inhibition-mitigates-ischemia-reperfusion-elicited-calpain-activation-and-the-damage-to-membrane-skeleton-proteins-in-isolated-rat-hearts
#9
Ling-Heng Kong, Xiao-Ming Gu, Feng Wu, Zhen-Xiao Jin, Jing-Jun Zhou
Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) has been implicated in myocardial ischemia/reperfusion (IR) injury. The aim of this study was to determine the effect of CaMKII on the damage to membrane skeleton proteins, which is an important cause of IR injury. Isolated rat hearts were subjected to 45-min global ischemia/2-h reperfusion. Both KN-62 and KN-93 were used to inhibit CaMKII. Compared with controls, the hearts in the IR group exhibited remarkable myocardial injury area, LDH release, cell apoptosis and contractile dysfunction, along with an increase in the phosphorylation of CaMKII and its substrate phospholamban...
September 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28735419/modulation-of-human-kv4-3-kchip2-channel-inactivation-kinetics-by-cytoplasmic-ca%C3%A2-%C3%A2-%C2%BA
#10
Christiane Groen, Robert Bähring
The transient outward current (I to) in the human heart is mediated by Kv4.3 channels complexed with Kv channel interacting protein (KChIP) 2, a cytoplasmic Ca(2+)-binding EF-hand protein known to modulate Kv4.3 inactivation gating upon heterologous co-expression. We studied Kv4.3 channels co-expressed with wild-type (wt) or EF-hand-mutated (?EF) KChIP2 in human embryonic kidney (HEK) 293 cells. Co-expression took place in the absence or presence of BAPTA-AM, and macroscopic currents were recorded in the whole-cell patch-clamp configuration with different free Ca(2+) concentrations in the patch-pipette...
July 22, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28558386/periodic-mechanical-stress-induces-chondrocyte-proliferation-and-matrix-synthesis-via-camkii-mediated-pyk2-signaling
#11
Wenwei Liang, Zeng Li, Zhen Wang, Jinchun Zhou, Huanghe Song, Shun Xu, Weiding Cui, Qing Wang, Zhefeng Chen, Feng Liu, Weimin Fan
BACKGROUND/AIMS: Periodic mechanical stress can promote chondrocyte proliferation and matrix synthesis to improve the quality of tissue-engineered cartilage. Although the integrin β1-ERK1/2 signal cascade has been implicated in periodic mechanical stress-induced mitogenic effects in chondrocytes, the precise mechanisms have not been fully established. The current study was designed to probe the roles of CaMKII and Pyk2 signaling in periodic mechanical stress-mediated chondrocyte proliferation and matrix synthesis...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28554967/basal-late-sodium-current-is-a-significant-contributor-to-the-duration-of-action-potential-of-guinea-pig-ventricular-myocytes
#12
Yejia Song, Luiz Belardinelli
In cardiac myocytes, an enhancement of late sodium current (INaL) under pathological conditions is known to cause prolongation of action potential duration (APD). This study investigated the contribution of INaL under basal, physiological conditions to the APD Whole-cell INaL and the APD of ventricular myocytes isolated from healthy adult guinea pigs were measured at 36°C. The INaL inhibitor GS967 or TTX was applied to block INaL The amplitude of basal INaL and the APD at 50% repolarization in myocytes stimulated at a frequency of 0...
May 2017: Physiological Reports
https://www.readbyqxmd.com/read/28436159/modulation-of-late-sodium-current-by-ca-2-calmodulin-dependent-protein-kinase-ii-protein-kinase-c-and-ca-2-during-hypoxia-in-rabbit-ventricular-myocytes
#13
Chen Fu, Jie Hao, Mengliu Zeng, Yejia Song, Wanzhen Jiang, Peihua Zhang, Antao Luo, Zhenzhen Cao, Luiz Belardinelli, Jihua Ma
What is the central question of this study? Hypoxia-induced increase in late sodium current (INa,L ) is associated with conditions causing cellular Ca(2+) overload and contributes to arrhythmogenesis in the ventricular myocardium. The INa,L is an important drug target. We investigated intracellular signal transduction pathways involved in modulation of INa,L during hypoxia. What is the main finding and its importance? Hypoxia caused increases in INa,L , reverse Na(+) -Ca(2+) exchange current and diastolic [Ca(2+) ], which were attenuated by inhibitors of Ca(2+) -calmodulin-dependent protein kinase II (CaMKII) and protein kinase C and by a Ca(2+) chelator...
July 1, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28431901/clozapine-reduces-toll-like-receptor-4-nf-%C3%AE%C2%BAb-mediated-inflammatory-responses-through-inhibition-of-calcium-calmodulin-dependent-akt-activation-in-microglia
#14
Seunghyun Jeon, Se Hyun Kim, Soon Young Shin, Young Han Lee
Clozapine is an atypical antipsychotic agent used in the treatment of schizophrenia and severe mood disorders. Accumulating evidence suggests that neuroinflammation is closely associated with the pathogenesis of various neurodegenerative diseases and psychiatric disorders. Clozapine exerts anti-inflammatory activity. However, the molecular mechanism underlying the anti-inflammatory activity of clozapine is poorly understood. In this study, we found that clozapine suppressed lipopolysaccharide (LPS)-induced phosphorylation of IκBα at Ser-32 and of p65/RelA at Ser-468, as well as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-dependent transcriptional activity in microglial cells...
April 18, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28352365/heart-failure-modulates-electropharmacological-characteristics-of-sinoatrial-nodes
#15
Shih-Lin Chang, Hui-Lun Chuang, Yao-Chang Chen, Yu-Hsun Kao, Yung-Kuo Lin, Yung-Hsin Yeh, Shih-Ann Chen, Yi-Jen Chen
The impact of heart failure (HF) on sinoatrial node (SAN) channel regulation and electropharmacological responses has remained elusive. The present study aimed to investigate the effects of HF on the electrical activity of SANs with and without pharmacological interventions. Action potentials (APs) were recorded in isolated SANs from normal rabbits (control) and those with HF (rapid ventricular pacing for 4 weeks) prior to and after administration of a funny current blocker (ivabradine; 0.1, 0.3, 3 or 10 µM), a calmodulin kinase II inhibitor (KN-93; 0...
February 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28346321/growth-arrest-and-dna-damage-inducible-protein-45%C3%AE-mediated-dna-demethylation-of-voltage-dependent-t-type-calcium-channel-3-2-subunit-enhances-neuropathic-allodynia-after-nerve-injury-in-rats
#16
Cheng-Yuan Lai, Ming-Chun Hsieh, Yu-Cheng Ho, An-Sheng Lee, Hsueh-Hsiao Wang, Jen-Kun Cheng, Yat-Pang Chau, Hsien-Yu Peng
BACKGROUND: Growth arrest and DNA-damage-inducible protein 45β reactivates methylation-silenced neural plasticity-associated genes through DNA demethylation. However, growth arrest and DNA-damage-inducible protein 45β-dependent demethylation contributes to neuropathic allodynia-associated spinal plasticity remains unclear. METHODS: Adult male Sprague-Dawley rats (654 out of 659) received a spinal nerve ligation or a sham operation with or without intrathecal application of one of the following: growth arrest and DNA-damage-inducible protein 45β messenger RNA-targeted small interfering RNA, lentiviral vector expressing growth arrest and DNA-damage-inducible protein 45β, Ro 25-6981 (an NR2B-bearing N-methyl-D-aspartate receptor antagonist), or KN-93 (a calmodulin-dependent protein kinase II antagonist) were used for behavioral measurements, Western blotting, immunofluorescence, dot blots, detection of unmodified cytosine enrichment at cytosine-phosphate-guanine site, chromatin immunoprecipitation quantitative polymerase chain reaction analysis, and slice recordings...
June 2017: Anesthesiology
https://www.readbyqxmd.com/read/28257804/characterization-and-cellular-localization-of-human-5-lipoxygenase-and-its-protein-isoforms-5-lo%C3%AE-13-5-lo%C3%AE-4-and-5-lop12
#17
Ann-Katrin Ball, Kim Beilstein, Sandra Wittmann, Duran Sürün, Meike J Saul, Frank Schnütgen, Nicolas Flamand, Ricardo Capelo, Astrid S Kahnt, Helena Frey, Liliana Schaefer, Rolf Marschalek, Ann-Kathrin Häfner, Dieter Steinhilber
Human 5-lipoxygenase (5-LO-WT) initiates the leukotriene (LT) biosynthesis. LTs play an important role in diseases like asthma, atherosclerosis and in many types of cancer. In this study, we investigated the 5-LO isoforms 5-LO∆13, 5-LO∆4 and 5-LOp12, lacking the exons 13, 4 or a part of exon 12, respectively. We were able to detect the mRNA of the isoforms 5-LO∆13 and 5-LOp12 in B and T cell lines as well as in primary B and T cells and monocytes. Furthermore, we found that expression of 5-LO and particularly of the 5-LO∆13 and 5-LOp12 isoforms is increased in monocytes from patients with rheumatoid arthritis and sepsis...
May 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28130334/blockade-of-camkii-depresses-conduction-preferentially-in-the-right-ventricular-outflow-tract-and-promotes-ischemic-ventricular-fibrillation-in-the-rabbit-heart
#18
Mark Warren, Katie J Sciuto, Tyson G Taylor, Vivek Garg, Natalia S Torres, Junko Shibayama, Kenneth W Spitzer, Alexey V Zaitsev
Calcium/calmodulin-dependent protein kinase II (CaMKII) regulates the principle ion channels mediating cardiac excitability and conduction, but how this regulation translates to the normal and ischemic heart remains unknown. Diverging results on CaMKII regulation of Na(+) channels further prevent predicting how CaMKII activity regulates excitability and conduction in the intact heart. To address this deficiency, we tested the effects of the CaMKII blocker KN93 (1 and 2.75 μM) and its inactive analog KN92 (2...
April 1, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28097237/oxidized-camkii-promotes-asthma-through-the-activation-of-mast-cells
#19
Jingjing Qu, Danh C Do, Yufeng Zhou, Elizabeth Luczak, Wayne Mitzner, Mark E Anderson, Peisong Gao
Oxidation of calmodulin-dependent protein kinase II (ox-CaMKII) by ROS has been associated with asthma. However, the contribution of ox-CaMKII to the development of asthma remains to be fully characterized. Here, we tested the effect of ox-CaMKII on IgE-mediated mast cell activation in an allergen-induced mouse model of asthma using oxidant-resistant CaMKII MMVVδ knockin (MMVVδ) mice. Compared with WT mice, the allergen-challenged MMVVδ mice displayed less airway hyperresponsiveness (AHR) and inflammation...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28094445/presynaptic-inhibition-of-transient-receptor-potential-vanilloid-type-1-trpv1-receptors-by-noradrenaline-in-nociceptive-neurons
#20
Saikat Chakraborty, Vincent Elvezio, Martin Kaczocha, Mario Rebecchi, Michelino Puopolo
KEY POINTS: The transient receptor potential vanilloid type 1 (TRPV1) receptor is a polymodal molecular integrator in the pain pathway expressed in Aδ- and C-fibre nociceptors and is responsible for the thermal hyperalgesia associated with inflammatory pain. Noradrenaline strongly inhibited the activity of TRPV1 channels in dorsal root ganglia neurons. The effect of noradrenaline was reproduced by clonidine and antagonized by yohimbine, consistent with contribution of α2 adrenergic receptors...
April 15, 2017: Journal of Physiology
keyword
keyword
100575
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"