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https://www.readbyqxmd.com/read/28701796/camk-ii-%C3%AE-down-regulation-protects-dorsal-root-ganglion-neurons-from-ropivacaine-hydrochloride-neurotoxicity
#1
Xian-Jie Wen, Xiao-Hong Li, Heng Li, Hua Liang, Chen-Xiang Yang, Han-Bing Wang
T-type calcium channels are intimately involved in the local anesthetics neurotoxicity. Does CaMKIIγ regulate T-type calcium currents in local anesthetics neurotoxicity? This study generated pAd-CaMKIIγ and pAd-shRNA adenovirus vectors to up- and down-regulate CaMKIIγ mRNA expression in dorsal root ganglion neurons (DRG). Normal DRG (Normal group), empty vector DRG (Empty vector group), pAd-CaMKIIγ DRG (pAd-CaMKIIγ group) and pAd-shRNA DRG (pAd-shRNA group) were treated or untreated with 3 mM ropivacaine hydrochloride for 4 h...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28698220/activation-of-camkiv-by-soluble-amyloid-%C3%AE-1-42-impedes-trafficking-of-axonal-vesicles-and-impairs-activity-dependent-synaptogenesis
#2
Daehun Park, Myeongsu Na, Jung Ah Kim, Unghwi Lee, Eunji Cho, Mirye Jang, Sunghoe Chang
The prefibrillar form of soluble amyloid-β (sAβ1-42) impairs synaptic function and is associated with the early phase of Alzheimer's disease (AD). We investigated how sAβ1-42 led to presynaptic defects using a quantum dot-based, single particle-tracking method to monitor synaptic vesicle (SV) trafficking along axons. We found that sAβ1-42 prevented new synapse formation induced by chemical long-term potentiation (cLTP). In cultured rat hippocampal neurons, nanomolar amounts of sAβ1-42 impaired Ca(2+) clearance from presynaptic terminals and increased the basal Ca(2+) concentration...
July 11, 2017: Science Signaling
https://www.readbyqxmd.com/read/28697452/effect-of-fluoride-exposure-on-mrna-expression-of-cav1-2-and-calcium-signal-pathway-apoptosis-regulators-in-pc12-cells
#3
Qiuxia Liao, Rui Zhang, Xiaoyu Wang, Weiwei Nian, Lulu Ke, Wei Ouyang, Zigui Zhang
This study investigated the effects of fluoride exposure on the mRNA expression of Cav1.2 calcium signaling pathway and apoptosis regulatory molecules in PC12 cells. The viability of PC12 cell receiving high fluoride (5.0mM) and low fluoride (0.5mM) alone or fluoride combined with L-type calcium channel (LTCC) agonist/inhibitor (5umol/L FPL6417/2umol/L nifedipine) was detected using cell counting kit-8 at different time points (2, 4, 6, 8, 12, 10, and 24h). Changes in the cell configuration were observed after exposing the cells to fluoride for 24h...
June 30, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28637792/reactive-sulfur-species-inactivate-ca-2-calmodulin-dependent-protein-kinase-iv-via-s-polysulfidation-of-its-active-site-cysteine-residue
#4
Tsuyoshi Takata, Hideshi Ihara, Naoya Hatano, Yukihiro Tsuchiya, Takaaki Akaike, Yasuo Watanabe
Reactive sulfur species (RSS) modulate protein functions via S- polysulfidation of reactive Cys residues. Here, we report that Ca(2+)/calmodulin (CaM)-dependent protein kinase IV (CaMKIV) was reversibly inactivated by RSS via polysulfidation of the active site Cys residue. CaMKIV is phosphorylated at Thr(196) by its upstream CaMK kinase (CaMKK), resulting in the induction of its full activity. In vitro incubation of CaMKIV with the exogenous RSS donors Na2Sn ( n = 2-4) resulted in dose-dependent inhibition of the CaMKK-induced phospho-Thr(196) and consequent inactivation of the enzyme activity...
June 21, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28633902/calcium-sensing-receptor-initiating-cystathionine-gamma-lyase-hydrogen-sulfide-pathway-to-inhibit-platelet-activation-in-hyperhomocysteinemia-rat
#5
Yuwen Wang, Ziqing Zhao, Sa Shi, Fei Gao, Jichao Wu, Shiyun Dong, Weihua Zhang, Yanhong Liu, Xin Zhong
Hyperhomocysteinemia (HHcy, high homocysteine) induces the injury of endothelial cells (ECs). Hydrogen sulfide (H2S) protects ECs and inhibits the activation of platelets. Calcium-sensing receptor (CaSR) regulates the production of endogenous H2S. However, whether CaSR inhibits the injury of ECs and the activation of platelets by regulating the endogenous cystathionine-gamma-lyase (CSE, a major enzyme that produces H2S)/H2S pathway in hyperhomocysteinemia has not been previously investigated. Here, we tested the ultrastructure alterations of ECs and platelets, the changes in the concentration of serum homocysteine and the parameters of blood of hyperhomocysteinemia rats were measured...
June 19, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28615325/calcium-calmodulin-dependent-protein-kinase-regulates-the-pink1-parkin-and-dj-1-pathways-of-mitophagy-during-sepsis
#6
Xianghong Zhang, Du Yuan, Qian Sun, Li Xu, Emma Lee, Anthony J Lewis, Brian S Zuckerbraun, Matthew R Rosengart
During sepsis and shock states, mitochondrial dysfunction occurs. Consequently, adaptive mechanisms, such as fission, fusion, and mitophagy, are induced to eliminate damaged portions or entire dysfunctional mitochondria. The regulatory PINK1/Parkin and DJ-1 pathways are strongly induced by mitochondrial depolarization, although a direct link between loss of mitochondrial membrane potential (ΔΨ) and mitophagy has not been identified. Mitochondria also buffer Ca(2+), and their buffering capacity is dependent on ΔΨ...
June 14, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28590038/effects-of-estrogen-and-cimicifuga-racemosa-on-the-cardiac-norepinephrine-pathway-of-ovariectomized-rats
#7
Yao Liu, Jing Zhang, Shuya Liu, Wenjuan Wang, Xing Chen, Hai Jiang, Junlei Li, Ke Wang, Wenpei Bai, Haicheng Zhang, Lihua Qin
This study aimed to investigate the effects of estrogen and Cimicifuga racemosa on the stellate ganglion, cardiac norepinephrine pathway, and Ca(2+) /calmodulin-dependent protein kinase II (CaMK II). Forty adult female Sprague Dawley rats were randomly divided into four groups: SHAM, ovariectomized (OVX), ovariectomized with estrogen treatment (E2), and ovariectomized with Cimicifuga racemosa treatment (iCR). After 4 weeks of treatment, norepinephrine (NE) content was determined by high-performance liquid chromatography, and dopamine beta-hydroxylase (DBH) and norepinephrine transporter (NET) expression was detected by immunohistochemistry...
June 7, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28583581/the-regulation-of-skf38393-on-the-signaling-pathway-of-dopamine-d1-receptor-in-hippocampus-during-chronic-sleep-deprivation
#8
Si Chen, Xiaosa Wen, Han Liang, Yuxiang Li, Xinmin Chen, Dong Zhang, Rengfei Shi, Wenling Ma
BACKGROUND: Hippocampal functions are sensitive to sleep deficiency. Dopamine D1 receptor (D1R) in hippocampus can regulate the expression of cAMP response element binding protein (CREB) through PKA, MAPK and phosphoinositide pathway, but which pathway plays the major role in hippocampus during Chronic sleep deprivation (CSD) is unclear. METHODS: The CSD model was created, SKF rats were administered the D1R agonist (SKF38363), and hippocampus from each animal was dissected for following molecular detection...
July 27, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28573136/effects-of-wenxin-keli-on-cardiac-hypertrophy-and-arrhythmia-via-regulation-of-the-calcium-calmodulin-dependent-kinase-ii-signaling-pathway
#9
Xinyu Yang, Yu Chen, Yanda Li, Xiaomeng Ren, Yanwei Xing, Hongcai Shang
We investigated the effects of Wenxin Keli (WXKL) on the Calcium/Calmodulin dependent kinase II (CaMK II) signal transduction pathway with transverse aortic constriction (TAC) rats. Echocardiographic measurements were obtained 3 and 9 weeks after the surgery. Meanwhile, the action potentials (APDs) were recorded using the whole-cell patch clamp technique, and western blotting was used to assess components of the CaMK II signal transduction pathway. At both 3 and 9 weeks after treatment, the fractional shortening (FS%) increased in the WXKL group compared with the TAC group...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28570746/influence-of-extremely-low-frequency-magnetic-fields-on-ca-2-signaling-and-double-messenger-system-in-mice-hippocampus-and-reversal-function-of-procyanidins-extracted-from-lotus-seedpod
#10
Haihui Zhang, Yuanyuan Dai, Yanxiang Cheng, Yuanqing He, Zandile Manyakara, Yuqing Duan, Guibo Sun, Xiaobo Sun
This research investigated the influence of extremely low frequency magnetic fields (ELF-MF; 50 Hz, 8 mT, 4 h per day, for 28 days) on calcium ion signaling and the double messenger system in the hippocampus of mice. Messengers that were studied included: G-protein, Ins(1,4,5)P3 (IP3 ), diacylglycerol (DAG), cAMP-dependent protein kinase (PKA), and Ca(2+) -dependent protein kinase C (PKC). The results showed that ELF-MF caused an increase in the levels of Gi protein, IP3, DAG, PKA and PKC beta, calcium and calmodulin-dependent protein phosphatase calcineuring (PP2B), and intracellular Ca(2+) content, and a decrease in calcium/calmodulin-dependent protein kinase II (CaMK II) and PKC alpha...
June 1, 2017: Bioelectromagnetics
https://www.readbyqxmd.com/read/28566250/local-somatodendritic-translation-and-hyperphosphorylation-of-tau-protein-triggered-by-ampa-and-nmda-receptor-stimulation
#11
Shunsuke Kobayashi, Toru Tanaka, Yoshiyuki Soeda, Osborne F X Almeida, Akihiko Takashima
Tau is a major component of the neurofibrillary tangles (NFT) that represent a pathological hallmark of Alzheimer's disease (AD). Although generally considered an axonal protein, Tau is found in the somato-dendritic compartment of degenerating neurons and this redistribution is thought to be a trigger of neurodegeneration in AD. Here, we show the presence of tau mRNA in a dendritic ribonucleoprotein (RNP) complex that includes Ca2(+)-calmodulin dependent protein kinase (CaMK)IIα mRNA and that is translated locally in response to glutamate stimulation...
June 2017: EBioMedicine
https://www.readbyqxmd.com/read/28542873/a-map-of-the-phosphoproteomic-alterations-that-occur-after-a-bout-of-maximal-intensity-contractions
#12
Gregory K Potts, Rachel M McNally, Rocky Blanco, Jae-Sung You, Alexander S Hebert, Michael S Westphall, Joshua J Coon, Troy A Hornberger
The maintenance of skeletal muscle mass is essential for health and quality of life. It is well recognized that maximal-intensity contractions, such as those which occur during resistance exercise, promote an increase in muscle mass. Yet, the molecules that sense the mechanical information and convert it into the signalling events (e.g. phosphorylation) that drive the increase in muscle mass remain undefined. Here we describe a phosphoproteomics workflow to examine the effects of electrically evoked maximal-intensity contractions (MIC) on protein phosphorylation in mouse skeletal muscle...
May 25, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28535500/transient-receptor-potential-vanilloid-5-mediates-ca2-influx-and-inhibits-chondrocyte-autophagy-in-a-rat-osteoarthritis-model
#13
Yingliang Wei, Yanfang Wang, Yutong Wang, Lunhao Bai
BACKGROUND: Autophagy, a self-protective mechanism of chondrocytes, has become a promising target to impede the progress of osteoarthritis (OA). Autophagy is regulated by cytosolic Ca2+ activity and may thus be modified by the Ca2+ permeable transient receptor potential channel vanilloid 5 (TRPV5). Therefore, we investigated the potential role of TRPV5 in mediating Ca2+ influx and in inhibiting chondrocyte autophagy in a rat OA model. METHODS: The rat OA model was assessed by macroscopic and histological analyses...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28527717/inhibition-of-the-lateral-habenular-camk%C3%A2-abolishes-naloxone-precipitated-conditioned-place-aversion-in-morphine-dependent-mice
#14
Jing Wang, Min Li, Ping Wang, Yunhong Zha, Zhi He, Zicheng Li
Addictive substances mediate positive and negative states promoting compulsive drug use. However, substrates for aversive effects of drugs are not fully understood. We found that inactivation of the lateral habenula (LHb) by microinjection of tetrodotoxin (TTX) abolished naloxone-precipitated conditioned place aversion (CPA) in morphine-dependent mice. We also found that lateral habenular administration of KN-62, a specific inhibitor for calcium/calmodulin dependent protein kinase II (CaMKII), abolished naloxone-precipitated CPA in morphine-dependent mice...
July 13, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28465474/nanoparticle-mediated-dual-delivery-of-resveratrol-and-dap5-ameliorates-kidney-ischemia-reperfusion-injury-by-inhibiting-cell-apoptosis-and-inflammation
#15
Yong Xu, Bo Zhang, Da Xie, Yu Hu, Hai-Lun Li, Li-Li Zhong, Hong-Wu Wang, Wei Jiang, Zun-Ping Ke, Dong-Hui Zheng
Ischemia reperfusion (I/R) injury is a leading cause of acute kidney injury with high morbidity and mortality due to limited therapy. NMDA receptor inhibitor (DAP5) and resveratrol (Res) could ameliorate kidney I/R injury, but their use is limited by low aqueous solubility and poor stability. Here, we examined the potential protective effects of Res-DAP5 nanoparticles (NP) against renal I/R injury. Mice were subjected to renal ischemia for 30 min followed by reperfusion for 24 h. The results showed that Res-DAP5-NP could decreased serum creatinine (Cr) and urea nitrogen (BUN), alleviated tubular damage and oxidative stress...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445148/pkc-and-camk-ii-inhibitions-coordinately-rescue-ischemia-induced-gabaergic-neuron-dysfunction
#16
Li Huang, Chun Wang, Shidi Zhao, Rongjing Ge, Sudong Guan, Jin-Hui Wang
Cerebral ischemia leads to neuronal death for stroke, in which the imbalance between glutamatergic neurons and GABAergic neurons toward neural excitotoxicity is presumably involved. GABAergic neurons are vulnerable to pathological factors and impaired in an early stage of ischemia. The rescue of GABAergic neurons is expected to be the strategy to reserve ischemic neuronal impairment. As protein kinase C (PKC) and calmodulin-dependent protein kinase II (CaMK-II) are activated during ischemia, we have investigated whether the inhibitions of these kinases rescue the ischemic impairment of cortical GABAergic neurons...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28428622/inhibition-of-late-sodium-current-suppresses-calcium-related-ventricular-arrhythmias-by-reducing-the-phosphorylation-of-camk-ii-and-sodium-channel-expressions
#17
Xiao-Hong Wei, Shan-Dong Yu, Lu Ren, Si-Hui Huang, Qiao-Mei Yang, Ping Wang, Yan-Peng Chu, Wei Yang, Yan-Sheng Ding, Yong Huo, Lin Wu
Cardiac arrhythmias associated with intracellular calcium inhomeostasis are refractory to antiarrhythmic therapy. We hypothesized that late sodium current (I Na) contributed to the calcium-related arrhythmias. Monophasic action potential duration at 90% completion of repolarization (MAPD90) was significantly increased and ventricular arrhythmias were observed in hearts with increased intracellular calcium concentration ([Ca(2+)]i) by using Bay K 8644, and the increase became greater in hearts treated with a combination of ATX-II and Bay K 8644 compared to Bay K 8644 alone...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28378126/global-transcriptomic-analysis-of-induced-cardiomyocytes-predicts-novel-regulators-for-direct-cardiac-reprogramming
#18
Mahmood Talkhabi, Seyed Morteza Razavi, Ali Salari
Heart diseases are the most significant cause of morbidity and mortality in the world. De novo generated cardiomyocytes (CMs) are a great cellular source for cell-based therapy and other potential applications. Direct cardiac reprogramming is the newest method to produce CMs, known as induced cardiomyocytes (iCMs). During a direct cardiac reprogramming, also known as transdifferentiation, non-cardiac differentiated adult cells are reprogrammed to cardiac identity by forced expression of cardiac-specific transcription factors (TFs) or microRNAs...
June 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28371191/structure-based-target-specific-screening-leads-to-small-molecule-camkii-inhibitors
#19
David Xu, Liwei Li, Donghui Zhou, Degang Liu, Andy Hudmon, Samy O Meroueh
Target-specific scoring methods are more commonly used to identify small-molecule inhibitors among compounds docked to a target of interest. Top candidates that emerge from these methods have rarely been tested for activity and specificity across a family of proteins. In this study we docked a chemical library into CaMKIIδ, a member of the Ca(2+) /calmodulin (CaM)-dependent protein kinase (CaMK) family, and re-scored the resulting protein-compound structures using Support Vector Machine SPecific (SVMSP), a target-specific method that we developed previously...
May 9, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28344867/cd4-and-cd8-t-cells-are-both-needed-to-induce-paraneoplastic-neurological-disease-in-a-mouse-model
#20
Christina Gebauer, Béatrice Pignolet, Lidia Yshii, Emilie Mauré, Jan Bauer, Roland Liblau
Paraneoplastic neurological disorders (PNDs) are rare human autoimmune diseases that mostly affect the central nervous system (CNS). They are triggered by an efficient immune response against a neural self-antigen that is ectopically expressed in neoplastic tumors. Due to this shared antigenic expression, the immune system reacts not only to tumor cells but also to neural cells resulting in neurological damage. Growing data point to a major role of cell-mediated immunity in PNDs associated to autoantibodies against intracellular proteins...
2017: Oncoimmunology
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