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Calcium channel beta subunits

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https://www.readbyqxmd.com/read/28739256/palmitoylation-of-ca-2-channel-subunit-cav%C3%AE-2a-induces-pancreatic-beta-cell-toxicity-via-ca-2-overload
#1
Abdulla S Kazim, Petter Storm, Enming Zhang, Erik Renström
High blood glucose triggers the release of insulin from pancreatic beta cells, but if chronic, causes cellular stress, partly due to impaired Ca(2+) homeostasis. Ca(2+) influx is controlled by voltage-gated calcium channels (CaV) and high density of CaV in the plasma membrane could lead to Ca(2+) overload. Trafficking of the pore-forming CaVα1 subunit to the plasma membrane is regulated by auxiliary subunits, such as the CaVβ2a subunit. This study investigates, using Ca(2+) imaging and immunohistochemistry, the role of palmitoylation of CaVβ2a in maintaining Ca(2+) homeostasis and beta cell function...
September 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28697281/transport-of-the-alpha-subunit-of-the-voltage-gated-l-type-calcium-channel-through-the-sarcoplasmic-reticulum-occurs-prior-to-localization-to-triads-and-requires-the-beta-subunit-but-not-stac3-in-skeletal-muscles
#2
Jeremy W Linsley, I-Uen Hsu, Wenjia Wang, John Y Kuwada
Contraction of skeletal muscle is initiated by excitation-contraction (EC) coupling during which membrane voltage is transduced to intracellular Ca(2+) release. EC coupling requires L-type voltage gated Ca2+ channels (the dihydropyridine receptor or DHPR) located at triads, which are junctions between the transverse (T) tubule and sarcoplasmic reticulum (SR) membranes, that sense membrane depolarization in the T tubule membrane. Reduced EC coupling is associated with ageing, and disruptions of EC coupling result in congenital myopathies for which there are few therapies...
September 2017: Traffic
https://www.readbyqxmd.com/read/28637791/store-operated-calcium-entry-suppressed-tgf%C3%AE-1-smad3-signaling-pathway-in-glomerular-mesangial-cells
#3
Sarika Chaudhari, Weizu Li, Yanxia Wang, Hui Jiang, Yuhong Ma, Mark E Davis, Jonathan E Zuckerman, Rong Ma
Our previous study demonstrated that the abundance of extracellular matrix proteins was suppressed by store-operated Ca2+ entry in mesangial cells (MCs). The present study was conducted to investigate the underlying mechanism focused on the transforming growth factor beta 1 (TGFβ1) - Smad3 pathway, a critical pathway for ECM expansion in diabetic kidneys. We hypothesized that SOCE suppressed ECM protein expression by inhibiting this pathway in MCs. In cultured human MCs, we observed that TGFβ1 (5 ng/ml for 15 hours) significantly increased Smad3 phosphorylation as evaluated by immunoblot...
June 21, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28614222/next-generation-sequencing-identifies-pathogenic-and-modifier-mutations-in-a-consanguineous-chinese-family-with-hypertrophic-cardiomyopathy
#4
Xinlin Zhang, Jun Xie, Suhui Zhu, Yuhan Chen, Lian Wang, Biao Xu
Hypertrophic cardiomyopathy (HCM) is a highly heterogeneous disease displaying considerable interfamilial and intrafamilial phenotypic variation, including disease severity, age of onset, and disease progression. This poorly understood variance raises the possibility of genetic modifier effects, particularly in MYBPC3-associated HCM.In a large consanguineous Chinese HCM family, we identified 8 members harboring the MYBPC3 c.3624delC (p.Lys1209Serfs) disease-causing mutation, but with very disparate phenotypes...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28595796/the-metal-and-metalloprotein-profile-of-human-plasma-as-biomarkers-for-stroke-diagnosis
#5
Keaton S Nahan, Kyle B Walsh, Opeolu Adeoye, Julio A Landero-Figueroa
Stroke, a major cause of disability and mortality, affects someone in the United States every 40s. Stroke biomarkers, including those that could be used as a blood test for diagnosis of stroke, have been particularly elusive. We performed a double blind study to identify human plasma biomarkers for the diagnosis of stroke, including acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH). We utilized a three-track approach based on the total metal profile, the metal cofactor levels among metalloproteins, and the identification of stroke-related metalloproteins...
July 2017: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/28429615/regulation-of-vascular-large-conductance-calcium-activated-potassium-channels-by-nrf2-signalling
#6
Yong Li, Xiao-Li Wang, Xiaojing Sun, Qiang Chai, Jingchao Li, Benjamin Thompson, Win-Kuang Shen, Tong Lu, Hon-Chi Lee
BK channels are major ionic determinants of vasodilation. BK channel function is impaired in diabetic vessels due to accelerated proteolysis of its beta-1 (BK-β1) subunits in response to increased oxidative stress. The nuclear factor E2-related factor-2 (Nrf2) signalling pathway has emerged as a master regulator of cellular redox status, and we hypothesized that it plays a central role in regulating BK channel function in diabetic vessels. We found that Nrf2 expression was markedly reduced in db/db diabetic mouse aortas, and this was associated with significant downregulation of BK-β1...
April 1, 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/28424266/disease-associated-extracellular-loop-mutations-in-the-adhesion-g-protein-coupled-receptor-g1-adgrg1-gpr56-differentially-regulate-downstream-signaling
#7
Ayush Kishore, Randy A Hall
Mutations to the adhesion G protein-coupled receptor ADGRG1 (G1; also known as GPR56) underlie the neurological disorder bilateral frontoparietal polymicrogyria. Disease-associated mutations in G1 studied to date are believed to induce complete loss of receptor function through disruption of either receptor trafficking or signaling activity. Given that N-terminal truncation of G1 and other adhesion G protein-coupled receptors has been shown to significantly increase the receptors' constitutive signaling, we examined two different bilateral frontoparietal polymicrogyria-inducing extracellular loop mutations (R565W and L640R) in the context of both full-length and N-terminally truncated (ΔNT) G1...
June 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28384108/profiling-of-circulating-serum-micrornas-in-children-with-autism-spectrum-disorder-using-stem-loop-qrt-pcr-assay
#8
Tatyana M Kichukova, Nikolay T Popov, Ivan S Ivanov, Tihomir I Vachev
BACKGROUND: Development of biomarkers for autism spectrum disorder (ASD) has still remained a challenge to date. Recently, alterations of the expression of microRNAs (miRNAs) in peripheral blood, serum and post-mortem brain tissue have been linked to ASD. miRNAs are known to be secreted by various cell types and can mediate transmission of information into recipient cells and to modulate their physiological functions. On this basis it is assumed that circulating miRNAs could be useful biomarkers for the diagnosis or prognosis of pathological conditions...
March 1, 2017: Folia Medica
https://www.readbyqxmd.com/read/28351836/structural-and-biophysical-analyses-of-the-skeletal-dihydropyridine-receptor-%C3%AE-subunit-%C3%AE-1a-reveal-critical-roles-of-domain-interactions-for-stability
#9
Nicole C Norris, Soumya Joseph, Shouvik Aditya, Yamuna Karunasekara, Philip G Board, Angela F Dulhunty, Aaron J Oakley, Marco G Casarotto
Excitation-contraction (EC) coupling in skeletal muscle requires a physical interaction between the voltage-gated calcium channel dihydropyridine receptor (DHPR) and the ryanodine receptor Ca(2+) release channel. Although the exact molecular mechanism that initiates skeletal EC coupling is unresolved, it is clear that both the α1 and β subunits of DHPR are essential for this process. Here, we employed a series of techniques, including size-exclusion chromatography-multi-angle light scattering, differential scanning fluorimetry, and isothermal calorimetry, to characterize various biophysical properties of the skeletal DHPR β subunit β1a Removal of the intrinsically disordered N and C termini and the hook region of β1a prevented oligomerization, allowing for its structural determination by X-ray crystallography...
May 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28289383/the-citrus-flavanone-naringenin-produces-cardioprotective-effects-in-hearts-from-1-year-old-rat-through-activation-of-mitobk-channels
#10
Lara Testai, Eleonora Da Pozzo, Ilaria Piano, Luisa Pistelli, Claudia Gargini, Maria Cristina Breschi, Alessandra Braca, Claudia Martini, Alma Martelli, Vincenzo Calderone
Background and Purpose: Incidence of cardiovascular disorders increases with age, because of a dramatic fall of endogenous self-defense mechanisms and increased vulnerability of myocardium. Conversely, the effectiveness of many cardioprotective drugs is blunted in hearts of 1 year old rat. The Citrus flavanone naringenin (NAR) was reported to promote cardioprotective effects against ischemia/reperfusion (I/R) injury, through the activation of mitochondrial large conductance calcium-activated potassium channel (mitoBK)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27981446/comparative-capability-of-menstrual-blood-versus-bone-marrow-derived-stem-cells-in-neural-differentiation
#11
COMPARATIVE STUDY
Fereshteh Azedi, Somaieh Kazemnejad, Amir Hassan Zarnani, Masoud Soleimani, Amir Shojaei, Shaghayegh Arasteh
In order to characterize the potency of menstrual blood stem cells (MenSCs) for future cell therapy of neurological disorders instead of bone marrow stem cells (BMSCs) as a well-known and conventional source of adult stem cells, we examined the in vitro differentiation potential of these stem cells into neural-like cells. The differentiation potential of MenSCs to neural cells in comparison with BMSCs was assessed under two step neural differentiation including conversion to neurosphere-like cells and final differentiation...
February 2017: Molecular Biology Reports
https://www.readbyqxmd.com/read/27660282/cross-talk-between-macrophages-and-atrial-myocytes-in-atrial-fibrillation
#12
Zewei Sun, Dongchen Zhou, Xudong Xie, Shuai Wang, Zhen Wang, Wenting Zhao, Hongfei Xu, Liangrong Zheng
Increased macrophage accumulation occurs in the atria of patients with atrial fibrillation (AF). However, the phenotype and functions of the macrophages in AF remain unclear. We investigated the macrophage-atrial myocyte interaction in AF patients and found that the increased macrophages were mainly pro-inflammatory macrophages (iNOS(+), Arg1(-)). Tachypacing of HL-1 atrial myocytes also led to pro-inflammatory macrophage polarization. In addition, lipopolysaccharide (LPS)-stimulated pro-inflammatory macrophages-induced atrial electrical remodeling, evidenced by increased AF incidence and decreased atrial effective refractory period and L-type calcium currents (I Ca-L) in both canine and mouse AF models...
November 2016: Basic Research in Cardiology
https://www.readbyqxmd.com/read/27445978/intracellular-molecular-differences-in-aldosterone-compared-to-cortisol-secreting-adrenal-cortical-adenomas
#13
REVIEW
Eric Seidel, Ute I Scholl
The adrenal cortex is a major site of steroid hormone production. Two hormones are of particular importance: aldosterone, which is produced in the zona glomerulosa in response to volume depletion and hyperkalemia, and cortisol, which is produced in the zona fasciculata in response to stress. In both cases, acute stimulation leads to increased hormone production, and chronic stimulation causes hyperplasia of the respective zone. Aldosterone- and cortisol-producing adenomas (APAs and CPAs) are benign tumors of the adrenal cortex that cause excess hormone production, leading to primary aldosteronism and Cushing's syndrome, respectively...
2016: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/27440776/-pro-renin-receptor-regulates-potassium-homeostasis-through-a-local-mechanism
#14
Chuanming Xu, Aihua Lu, Hong Wang, Hui Fang, Li Zhou, Peng Sun, Tianxin Yang
(Pro)renin receptor (PRR) is highly expressed in the distal nephron with unclear functional implication. The present study was conducted to explore a potential role of renal PRR during high K+ (HK) loading. In normal Sprague-Dawley rats, a 1-week HK intake increased renal expression of full-length PRR and urinary excretion of soluble PRR (sPRR). Administration of PRO20, a decoy peptide antagonist of PRR, to K+-loaded animals elevated plasma K+ level and decreased urinary K+ excretion, accompanied with suppressed aldosterone excretion...
July 20, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27238266/modulation-of-bk-channels-by-ethanol
#15
REVIEW
A M Dopico, A N Bukiya, G Kuntamallappanavar, J Liu
In alcohol-naïve systems, ethanol (<100mM) exposure of calcium-gated BK channels perturbs physiology and behavior. Brief (several minutes) ethanol exposure usually leads to increased BK current, which results from ethanol interaction with a pocket mapped to the BK channel-forming slo1 protein cytosolic tail domain. The importance of this region in ethanol-induced intoxication has been independently supported by an unbiased screen of Caenorhabditis elegans slo1 mutants. However, ethanol-induced BK activation is not universal as refractoriness and inhibition have been reported...
2016: International Review of Neurobiology
https://www.readbyqxmd.com/read/27123484/paroxysmal-hypnogenic-dyskinesia-is-associated-with-mutations-in-the-prrt2-gene
#16
Xiao-Rong Liu, Dan Huang, Jie Wang, Yi-Fan Wang, Hui Sun, Bin Tang, Wen Li, Jin-Xing Lai, Na He, Mei Wu, Tao Su, Heng Meng, Yi-Wu Shi, Bing-Mei Li, Bei-Sha Tang, Wei-Ping Liao
OBJECTIVE: To explore the potential causative genes of paroxysmal hypnogenic dyskinesia (PHD), which was initially considered a subtype of paroxysmal dyskinesia and has been recently considered a form of nocturnal frontal lobe epilepsy (NFLE). METHODS: Eleven patients with PHD were recruited. Mutations in proline-rich region transmembrane protein-2 (PRRT2), myofibrillogenesis regulator 1 (MR-1), solute carrier family 2, member 1 (SLC2A1), calcium-activated potassium channel alpha subunit (KCNMA1), cholinergic receptor, nicotinic, alpha 4 (CHRNA4), cholinergic receptor, nicotinic, beta 2 (CHRNB2), cholinergic receptor, nicotinic, alpha 2 (CHRNA2), and potassium channel subfamily T member 1 (KCNT1) were screened by direct sequencing...
April 2016: Neurology. Genetics
https://www.readbyqxmd.com/read/26989572/essential-tremor-what-we-can-learn-from-current-pharmacotherapy
#17
REVIEW
William Ondo
BACKGROUND: The pathophysiology of essential tremor, especially at the cellular level, is poorly understood. Although no drug has been specifically designed to treat essential tremor, several medications improve tremor, and others worsen it. Studying the mechanism of actions of these medications can help our understanding of tremor pathophysiology and contribute to future rational drug design. METHODS: We reviewed literature, concentrating on mechanisms of action, of various medications that mitigate tremor...
2016: Tremor and Other Hyperkinetic Movements
https://www.readbyqxmd.com/read/26960935/inhibition-of-store-operated-calcium-entry-by-sub-lethal-levels-of-proteasome-inhibition-is-associated-with-stim1-stim2-degradation
#18
Xiu-Li Kuang, Yimei Liu, Yuhua Chang, Jing Zhou, He Zhang, Yiping Li, Jia Qu, Shengzhou Wu
Dysfunction of the ubiquitin-proteasome system (UPS) and calcium homeostasis has been implicated in the neurodegeneration of Alzheimer's and Parkinson's diseases. The cytosolic calcium concentration is maintained by store-operated calcium entry (SOCE), which is repressed by Alzheimer's disease-associated mutants, such as mutant presenilins. We hypothesized that inhibition of UPS impacts SOCE. This study showed that pretreatment with sub-lethal levels of proteasome inhibitors, including MG-132 and clasto-lactacystin-β-lactone (LA), reduced SOCE after depletion of endoplasmic reticulum calcium in rat neurons...
2016: Cell Calcium
https://www.readbyqxmd.com/read/26453278/calcium-signaling-properties-of-a-thyrotroph-cell-line-mouse-t%C3%AE-t1-cells
#19
Melanija Tomić, Paula Bargi-Souza, Elias Leiva-Salcedo, Maria Tereza Nunes, Stanko S Stojilkovic
TαT1 cells are mouse thyrotroph cell line frequently used for studies on thyroid-stimulating hormone beta subunit gene expression and other cellular functions. Here we have characterized calcium-signaling pathways in TαT1 cells, an issue not previously addressed in these cells and incompletely described in native thyrotrophs. TαT1 cells are excitable and fire action potentials spontaneously and in response to application of thyrotropin-releasing hormone (TRH), the native hypothalamic agonist for thyrotrophs...
December 2015: Cell Calcium
https://www.readbyqxmd.com/read/26224839/na-k-atpase-%C3%AE-3-is-a-death-target-of-alzheimer-patient-amyloid-%C3%AE-assembly
#20
Takayuki Ohnishi, Masako Yanazawa, Tomoya Sasahara, Yasuki Kitamura, Hidekazu Hiroaki, Yugo Fukazawa, Isao Kii, Takashi Nishiyama, Akiyoshi Kakita, Hiroyuki Takeda, Akihide Takeuchi, Yoshie Arai, Akane Ito, Hitomi Komura, Hajime Hirao, Kaori Satomura, Masafumi Inoue, Shin-ichi Muramatsu, Ko Matsui, Mari Tada, Michio Sato, Eri Saijo, Yoshiki Shigemitsu, Satoko Sakai, Yoshitaka Umetsu, Natsuko Goda, Naomi Takino, Hitoshi Takahashi, Masatoshi Hagiwara, Tatsuya Sawasaki, Genji Iwasaki, Yu Nakamura, Yo-ichi Nabeshima, David B Teplow, Minako Hoshi
Neurodegeneration correlates with Alzheimer's disease (AD) symptoms, but the molecular identities of pathogenic amyloid β-protein (Aβ) oligomers and their targets, leading to neurodegeneration, remain unclear. Amylospheroids (ASPD) are AD patient-derived 10- to 15-nm spherical Aβ oligomers that cause selective degeneration of mature neurons. Here, we show that the ASPD target is neuron-specific Na(+)/K(+)-ATPase α3 subunit (NAKα3). ASPD-binding to NAKα3 impaired NAKα3-specific activity, activated N-type voltage-gated calcium channels, and caused mitochondrial calcium dyshomeostasis, tau abnormalities, and neurodegeneration...
August 11, 2015: Proceedings of the National Academy of Sciences of the United States of America
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