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Mengna Chi, Hamish Evans, Jackson Gilchrist, Jack Mayhew, Alexander Hoffman, Elizabeth Ann Pearsall, Helen Jankowski, Joshua Stephen Brzozowski, Kathryn Anne Skelding
Calcium/calmodulin-stimulated protein kinase II (CaMKII) is a multi-functional kinase that controls a range of cellular functions, including proliferation, differentiation and apoptosis. The biological properties of CaMKII are regulated by multi-site phosphorylation. However, the role that CaMKII phosphorylation plays in cancer cell metastasis has not been examined. We demonstrate herein that CaMKII expression and phosphorylation at T286 is increased in breast cancer when compared to normal breast tissue, and that increased CAMK2 mRNA is associated with poor breast cancer patient prognosis (worse overall and distant metastasis free survival)...
2016: Scientific Reports
Paula Fernandes Aguiar, Sílvia Mourão Magalhães, Ivana Alice Teixeira Fonseca, Vanessa Batista da Costa Santos, Mariana Aguiar de Matos, Marco Fabrício Dias Peixoto, Fábio Yuzo Nakamura, Craig Crandall, Hygor Nunes Araújo, Leonardo Reis Silveira, Etel Rocha-Vieira, Flávio de Castro Magalhães, Fabiano Trigueiro Amorim
This study aims to evaluate the effect of regular post-exercise cold water immersion (CWI) on intramuscular markers of cellular stress response and signaling molecules related to mitochondria biogenesis and exercise performance after 4 weeks of high intensity interval training (HIIT). Seventeen healthy subjects were allocated into two groups: control (CON, n = 9) or CWI (n = 8). Each HIIT session consisted of 8-12 cycling exercise stimuli (90-110 % of peak power) for 60 s followed by 75 s of active recovery three times per week, for 4 weeks (12 HIIT sessions)...
September 2016: Cell Stress & Chaperones
Qian Wang, Wenjing Guo, Baixia Hao, Xianli Shi, Yingying Lu, Connie W M Wong, Victor W S Ma, Timothy T C Yip, Joseph S K Au, Quan Hao, King-Ho Cheung, Wutian Wu, Gui-Rong Li, Jianbo Yue
Reactive oxygen species (ROS) have been commonly accepted as inducers of autophagy, and autophagy in turn is activated to relieve oxidative stress. Yet, whether and how oxidative stress, generated in various human pathologies, regulates autophagy remains unknown. Here, we mechanistically studied the role of TRPM2 (transient receptor potential cation channel subfamily M member 2)-mediated Ca(2+) influx in oxidative stress-mediated autophagy regulation. On the one hand, we demonstrated that oxidative stress triggered TRPM2-dependent Ca(2+) influx to inhibit the induction of early autophagy, which renders cells more susceptible to death...
August 2, 2016: Autophagy
Hui Yu, Xinxin You, Jia Li, Hankui Liu, Zining Meng, Ling Xiao, Haifa Zhang, Hao-Ran Lin, Yong Zhang, Qiong Shi
Mapping of quantitative trait loci (QTL) is essential for the discovery of genetic structures that related to complex quantitative traits. In this study, we identified 264,072 raw SNPs (single-nucleotide polymorphisms) by double digest restriction site associated DNA sequencing (ddRADseq), and utilized 3029 of these SNPs to construct a genetic linkage map in orange-spotted grouper (Epinephelus coioides) using a regression mapping algorithm. The genetic map contained 24 linkage groups (LGs) spanning a total genetic distance of 1231...
2016: International Journal of Molecular Sciences
Jorge Vaquero-Garcia, Alejandro Barrera, Matthew R Gazzara, Juan González-Vallinas, Nicholas F Lahens, John B Hogenesch, Kristen W Lynch, Yoseph Barash
Alternative splicing (AS) can critically affect gene function and disease, yet mapping splicing variations remains a challenge. Here, we propose a new approach to define and quantify mRNA splicing in units of local splicing variations (LSVs). LSVs capture previously defined types of alternative splicing as well as more complex transcript variations. Building the first genome wide map of LSVs from twelve mouse tissues, we find complex LSVs constitute over 30% of tissue dependent transcript variations and affect specific protein families...
2016: ELife
Grace R Williams, Jennifer R Bethard, Mary N Berkaw, Alexis K Nagel, Louis M Luttrell, Lauren E Ball
The type 1 parathyroid hormone receptor (PTH1R) is a key regulator of calcium homeostasis and bone turnover. Here, we employed SILAC-based quantitative mass spectrometry and bioinformatic pathways analysis to examine global changes in protein phosphorylation following short-term stimulation of endogenously expressed PTH1R in osteoblastic cells in vitro. Following 5min exposure to the conventional agonist, PTH(1-34), we detected significant changes in the phosphorylation of 224 distinct proteins. Kinase substrate motif enrichment demonstrated that consensus motifs for PKA and CAMK2 were the most heavily upregulated within the phosphoproteome, while consensus motifs for mitogen-activated protein kinases were strongly downregulated...
January 1, 2016: Methods: a Companion to Methods in Enzymology
Ramesh Chandra, T Chase Francis, Prasad Konkalmatt, Ariunzaya Amgalan, Amy M Gancarz, David M Dietz, Mary Kay Lobo
An imbalance in molecular signaling cascades and transcriptional regulation in nucleus accumbens (NAc) medium spiny neuron (MSN) subtypes, those enriched in dopamine D1 versus D2 receptors, is implicated in the behavioral responses to psychostimulants. To provide further insight into the molecular mechanisms occurring in MSN subtypes by cocaine, we examined the transcription factor early growth response 3 (Egr3). We evaluated Egr3 because it is a target of critical cocaine-mediated signaling pathways and because Egr3-binding sites are found on promoters of key cocaine-associated molecules...
May 20, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Anthony J Sadler, Bandar A Suliman, Liang Yu, Xiangliang Yuan, Die Wang, Aaron T Irving, Soroush T Sarvestani, Ashish Banerjee, Ashley S Mansell, Jun-Ping Liu, Steve Gerondakis, Bryan R G Williams, Dakang Xu
To date, the activities of protein kinases have formed the core of our understanding of cell signal transduction. Comprehension of the extent of protein acetylation has raised expectations that this alternate post-transcriptional modification will be shown to rival phosphorylation in its importance in mediating cellular responses. However, limited instances have been identified. Here we show that signalling from Toll-like or TNF-α receptors triggers the calcium/calmodulin-dependent protein kinase (CaMK2) to activate histone acetyltransferase-1 (HAT1), which then acetylates the transcriptional regulator PLZF...
2015: Nature Communications
Isabel Martinez-Pena Y Valenzuela, Mohamed Aittaleb, Po-Ju Chen, Mohammed Akaaboune
A muscle-specific nonkinase anchoring protein (αkap), encoded within the calcium/calmodulin kinase II (camk2) α gene, was recently found to control the stability of acetylcholine receptor (AChR) clusters on the surface of cultured myotubes. However, it remains unknown whether this protein has any effect on receptor stability and the maintenance of the structural integrity of neuromuscular synapses in vivo. By knocking down the endogenous expression of αkap in mouse sternomastoid muscles with shRNA, we found that the postsynaptic receptor density was dramatically reduced, the turnover rate of receptors at synaptic sites was significantly increased, and the insertion rates of both newly synthesized and recycled receptors into the postsynaptic membrane were depressed...
April 1, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Shurei Sugita, Yoko Hosaka, Keita Okada, Daisuke Mori, Fumiko Yano, Hiroshi Kobayashi, Yuki Taniguchi, Yoshifumi Mori, Tomotake Okuma, Song Ho Chang, Manabu Kawata, Shuji Taketomi, Hirotaka Chikuda, Haruhiko Akiyama, Ryoichiro Kageyama, Ung-Il Chung, Sakae Tanaka, Hiroshi Kawaguchi, Shinsuke Ohba, Taku Saito
Notch signaling modulates skeletal formation and pathogenesis of osteoarthritis (OA) through induction of catabolic factors. Here we examined roles of Hes1, a transcription factor and important target of Notch signaling, in these processes. SRY-box containing gene 9 (Sox9)-Cre mice were mated with Hes1(fl/fl) mice to generate tissue-specific deletion of Hes1 from chondroprogenitor cells; this deletion caused no obvious abnormality in the perinatal period. Notably, OA development was suppressed when Hes1 was deleted from articular cartilage after skeletal growth in type II collagen (Col2a1)-Cre(ERT);Hes1(fl/fl) mice...
March 10, 2015: Proceedings of the National Academy of Sciences of the United States of America
Qi Xie, Qiulian Wu, Craig M Horbinski, William A Flavahan, Kailin Yang, Wenchao Zhou, Stephen M Dombrowski, Zhi Huang, Xiaoguang Fang, Yu Shi, Ashley N Ferguson, David F Kashatus, Shideng Bao, Jeremy N Rich
Brain tumor initiating cells (BTICs) co-opt the neuronal high affinity glucose transporter, GLUT3, to withstand metabolic stress. We investigated another mechanism critical to brain metabolism, mitochondrial morphology, in BTICs. BTIC mitochondria were fragmented relative to non-BTIC tumor cell mitochondria, suggesting that BTICs increase mitochondrial fission. The essential mediator of mitochondrial fission, dynamin-related protein 1 (DRP1), showed activating phosphorylation in BTICs and inhibitory phosphorylation in non-BTIC tumor cells...
April 2015: Nature Neuroscience
Sung Un Huh, Gil-Je Lee, Ji Hoon Jung, Yunsik Kim, Young Jin Kim, Kyung-Hee Paek
Plants are constantly exposed to pathogens and environmental stresses. To minimize damage caused by these potentially harmful factors, plants respond by massive transcriptional reprogramming of various stress-related genes via major transcription factor families. One of the transcription factor families, WRKY, plays an important role in diverse stress response of plants and is often useful to generate genetically engineered crop plants. In this study, we carried out functional characterization of CaWRKYa encoding group I WRKY member, which is induced during hypersensitive response (HR) in hot pepper (Capsicum annuum) upon Tobacco mosaic virus (TMV) infection...
2015: Scientific Reports
Xin-gang Yao, Xin Xu, Gai-hong Wang, Min Lei, Ling-ling Quan, Yan-hua Cheng, Ping Wan, Jin-pei Zhou, Jing Chen, Li-hong Hu, Xu Shen
Impaired glucose-stimulated insulin secretion (GSIS) and increasing β-cell death are two typical dysfunctions of pancreatic β-cells in individuals that are destined to develop type 2 diabetes, and improvement of β-cell function through GSIS enhancement and/or inhibition of β-cell death is a promising strategy for anti-diabetic therapy. In this study, we discovered that the small molecule, N-(2-benzoylphenyl)-5-bromo-2-thiophenecarboxamide (BBT), was effective in both potentiating GSIS and protecting β-cells from cytokine- or streptozotocin (STZ)-induced cell death...
March 2015: Journal of Endocrinology
Eun Young Lee, Shuji Kaneko, Promsuk Jutabha, Xilin Zhang, Susumu Seino, Takahito Jomori, Naohiko Anzai, Takashi Miki
Oral ingestion of carbohydrate triggers glucagon-like peptide 1 (GLP1) secretion, but the molecular mechanism remains elusive. By measuring GLP1 concentrations in murine portal vein, we found that the ATP-sensitive K(+) (KATP) channel is not essential for glucose-induced GLP1 secretion from enteroendocrine L cells, while the sodium-glucose co-transporter 1 (SGLT1) is required, at least in the early phase (5 min) of secretion. By contrast, co-administration of the α-glucosidase inhibitor (α-GI) miglitol plus maltose evoked late-phase secretion in a glucose transporter 2-dependent manner...
March 2015: Journal of Endocrinology
J Gu, A Y S Law, B H Y Yeung, C K C Wong
The expression of the Ca(2) (+)-sensing receptor (Casr) in the endocrine gland known as the corpuscle of Stannius (CS) regulates the secretion of the hypocalcemic hormone stanniocalcin-1 (STC1) to inhibit gill Ca(2) (+) uptake. Although numerous studies have reported the branchial expression of Casr and Stc1, the functions of these proteins in gills have not been elucidated yet. On the basis of recent findings regarding the autocrine/paracrine functions of STC1 in mammalian models, we proposed the hypothesis that branchial CaSR has an in situ 'sensing' function to regulate STC1 that maintains local Ca(2) (+) homeostasis...
October 2014: Journal of Molecular Endocrinology
Neelofar Mirza, Gohar Taj, Sandeep Arora, Anil Kumar
Finger millet (Eleusine coracana) variably accumulates calcium in different tissues, due to differential expression of genes involved in uptake, translocation and accumulation of calcium. Ca(2+)/H(+) antiporter (CAX1), two pore channel (TPC1), CaM-stimulated type IIB Ca(2+) ATPase and two CaM dependent protein kinase (CaMK1 and 2) homologs were studied in finger millet. Two genotypes GP-45 and GP-1 (high and low calcium accumulating, respectively) were used to understand the role of these genes in differential calcium accumulation...
October 25, 2014: Gene
Noah M Walton, Anoek de Koning, Xiuyuan Xie, Rick Shin, Qian Chen, Shinichi Miyake, Katsunori Tajinda, Adam K Gross, Jeffrey H Kogan, Carrie L Heusner, Kouichi Tamura, Mitsuyuki Matsumoto
In the postnatal hippocampus, newly generated neurons contribute to learning and memory. Disruptions in neurogenesis and neuronal development have been linked to cognitive impairment and are implicated in a broad variety of neurological and psychiatric disorders. To identify putative factors involved in this process, we examined hippocampal gene expression alterations in mice possessing a heterozygous knockout of the calcium/calmodulin-dependent protein kinase II alpha heterozygous knockout gene (CaMK2α-hKO), an established model of cognitive impairment that also displays altered neurogenesis and neuronal development...
September 2014: Stem Cells
Hong Geun Park, Hyun Sook Yu, Soyoung Park, Yong Min Ahn, Yong Sik Kim, Se Hyun Kim
The enzymatic activity of histone deacetylases (HDACs) leads to a histone deacetylation-mediated condensed chromatic structure, resulting in transcriptional repression, which has been implicated in the modifications of neural circuits and behaviors. Repeated treatment with electroconvulsive seizure (ECS) induces changes in histone acetylation, expression of various genes, and intrabrain cellular changes, including neurogenesis. In this study, we examined the effects of repeated ECS on the expression of class I HDACs and related changes in histone modifications and gene expression in the rat frontal cortex...
September 2014: International Journal of Neuropsychopharmacology
Davis Bradford, Viswanathan Raghuram, Justin L L Wilson, Chung-Lin Chou, Jason D Hoffert, Mark A Knepper, Trairak Pisitkun
In the renal collecting duct, binding of AVP to the V2 receptor triggers signaling changes that regulate osmotic water transport. Short-term regulation of water transport is dependent on vasopressin-induced phosphorylation of aquaporin-2 (AQP2) at Ser256. The protein kinase that phosphorylates this site is not known. We use Bayes' theorem to rank all 521 rat protein kinases with regard to the likelihood of a role in Ser256 phosphorylation on the basis of prior data and new experimental data. First, prior probabilities were estimated from previous transcriptomic and proteomic profiling data, kinase substrate specificity data, and evidence for kinase regulation by vasopressin...
July 15, 2014: American Journal of Physiology. Cell Physiology
Dong-An Su, Ri-Yue Jiang, Ning Liu, Liang-Cai Ding, DA-Ming Wang, Hai-Ying Yu, En-Shi Yan, Mei-Hua Zhu, Bin Zhu
Fluvoxamine, a common antidepressant agent, is designed to exert its pharmacological effect by inhibiting synaptic serotonin reuptake. However, increasing evidence has demonstrated that σ1 receptors are likely to be involved in the mechanism of action of fluvoxamine. The present study aimed to observe the effects of fluvoxamine on the expression levels of mammalian target of rapamycin (mTOR), Ca(2+)/calmodulin-dependent protein kinase 2γ (Camk2γ) and glycogen synthase kinase-3β (GSK-3β) in fluvoxamine-treated N2a cells and attempted to elucidate whether σ1 receptors mediate the pharmacological effects of fluvoxamine...
February 2014: Experimental and Therapeutic Medicine
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