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https://www.readbyqxmd.com/read/27891586/celastrol-attenuates-cadmium-induced-neuronal-apoptosis-via-inhibiting-ca-2-camkii-dependent-akt-mtor-pathway
#1
Ruijie Zhang, Yu Zhu, Xiaoqing Dong, Beibei Liu, Nana Zhang, Xiaoxue Wang, Lei Liu, Chong Xu, Shile Huang, Long Chen
Cadmium (Cd), an environmental and industrial pollutant, affects the nervous system and consequential neurodegenerative disorders. Recently we have shown that celastrol prevents Cd-induced neuronal cell death partially by suppressing Akt/mTOR pathway. However, the underlying mechanism remains to be elucidated. Here we show that celastrol attenuated Cd-elevated intracellular free calcium ([Ca(2+) ]i ) level and apoptosis in neuronal cells. Celastrol prevented Cd-induced neuronal apoptosis by inhibiting Akt-mediated mTOR pathway, as inhibition of Akt with Akt inhibitor X or ectopic expression of dominant negative Akt reinforced celastrol's prevention of Cd-induced phosphorylation of S6K1/4E-BP1 and cell apoptosis...
November 27, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27713141/fibroblast-growth-factor-23-dysregulates-late-sodium-current-and-calcium-homeostasis-with-enhanced-arrhythmogenesis-in-pulmonary-vein-cardiomyocytes
#2
Shih-Yu Huang, Yao-Chang Chen, Yu-Hsun Kao, Ming-Hsiung Hsieh, Yung-Kuo Lin, Cheng-Chih Chung, Ting-I Lee, Wen-Chin Tsai, Shih-Ann Chen, Yi-Jen Chen
Fibroblast growth factor 23 (FGF23), elevated in chronic renal failure, increases atrial arrhythmogenesis and dysregulates calcium homeostasis. Late sodium currents (INa-Late) critically induces ectopic activity of pulmoanry vein (the most important atrial fibrillation trigger). This study was to investigate whether FGF23 activates the INa-Late leading to calcium dysregulation and increases PV arrhythmogenesis. Patch clamp, western blot, and confocal microscopy were used to evaluate the electrical activities, calcium homeostasis, and mitochondrial reactive oxygen species (ROS) in PV cardiomyocytes with or without FGF23 (0...
October 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27648519/calcium-calmodulin-protein-kinase-ii-dependent-ryanodine-receptor-phosphorylation-mediates-cardiac-contractile-dysfunction-associated-with-sepsis
#3
Marisa Sepúlveda, Luis A Gonano, Manuel Viotti, Malena Morell, Paula Blanco, Micaela López Alarcón, Isalira Peroba Ramos, Adriana Bastos Carvalho, Emiliano Medei, Martín Vila Petroff
OBJECTIVES: Sepsis is associated with cardiac contractile dysfunction attributed to alterations in Ca handling. We examined the subcellular mechanisms involved in sarcoplasmic reticulum Ca loss that mediate altered Ca handling and contractile dysfunction associated with sepsis. DESIGN: Randomized controlled trial. SETTING: Research laboratory SUBJECTS:: Male wild type and transgenic mice INTERVENTIONS:: We induced sepsis in mice using the colon ascendens stent peritonitis model...
September 19, 2016: Critical Care Medicine
https://www.readbyqxmd.com/read/27611779/camkii-mediated-creb-phosphorylation-is-involved-in-ca2-induced-bdnf-mrna-transcription-and-neurite-outgrowth-promoted-by-electrical-stimulation
#4
Xiaodong Yan, Juanfang Liu, Zhengxu Ye, Jinghui Huang, Fei He, Wei Xiao, Xueyu Hu, Zhuojing Luo
Electrical stimulation (ES)-triggered up-regulation of brain-derived neurotrophic factor (BDNF) and neurite outgrowth in cultured rat postnatal dorsal root ganglion neurons (DRGNs) is calcium (Ca2+)-dependent. The effects of increased Ca2+ on BDNF up-regulation and neurite outgrowth remain unclear. We showed here that ES increased phosphorylation of the cAMP-response element binding protein (CREB). Blockade of Ca2+ suppressed CREB phosphorylation and neurite outgrowth. Down-regulation of phosphorylated (p)-CREB reduced BDNF transcription and neurite outgrowth triggered by ES...
2016: PloS One
https://www.readbyqxmd.com/read/27595397/curcumin-attenuates-retinal-vascular-leakage-by-inhibiting-calcium-calmodulin-dependent-protein-kinase-ii-activity-in-streptozotocin-induced-diabetes
#5
Jun Li, Peipei Wang, Jia Ying, Zhen Chen, Songping Yu
BACKGROUND: Curcumin possesses many pharmacological properties including anti-inflammatory effects. Although prior studies indicate that curcumin has beneficial effects for diabetic retinopathy, the mechanism of action is not known. To address this issue, we investigated the effect of curcumin against diabetes-induced retinal vascular damage and its mechanism of action by using cultured retinal Müller cells stimulated with high glucose. METHODS: We studied the effects of curcumin in vivo in the retinas of rats rendered diabetic by streptozotocin and in vitro in Müller cells stimulated with high glucose...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27451410/inhibition-of-camkii%C3%AE-in-the-central-nucleus-of-amygdala-attenuates-fentanyl-induced-hyperalgesia-in-rats
#6
Zhen Li, Chenhong Li, Pingping Yin, Zaijie Jim Wang, Fang Luo
Opioid-induced hyperalgesia (OIH) is a less-studied phenomenon that has been reported in both preclinical and clinical studies. Although the underlying cause is not entirely understood, OIH is a real-life problem that affects millions of patients on a daily basis. Research has implicated the important contribution of Ca(2+)/calmodulin-dependent protein kinase IIα (CaMKIIα) to OIH at the level of spinal nociceptors. To expand our understanding of the entire brain circuitry driving OIH, in this study we investigated the role of CaMKIIα in the laterocapcular division of the central amygdala (CeLC), the conjunctive point between the spinal cord and rostro-ventral medulla...
October 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27216039/inhibition-of-camkiv-relieves-streptozotocin-induced-diabetic-neuropathic-pain-through-regulation-of-hmgb1
#7
Xin Zhao, Le Shen, Li Xu, Zhiyao Wang, Chao Ma, Yuguang Huang
BACKGROUND: The pathogenesis of diabetic neuropathic pain is complicated and its underlying mechanisms remain unclear. Calmodulin-dependent protein kinases (CaMKs) IV (CaMKIV), one of CaMKs, regulates several transcription factors in pain mechanisms. High-mobility group box 1 (HMGB1) is a key mediator in diabetic neuropathic pain. This study aims to find the roles and mechanisms of CaMIV in diabetic neuropathic pain. METHODS: Diabetic animal models were constructed by injecting with streptozotocin (STZ) intraperitoneally...
2016: BMC Anesthesiology
https://www.readbyqxmd.com/read/27158118/enhancement-of-contraction-and-l-type-ca-2-current-by-murrayafoline-a-via-protein-kinase-c-in-rat-ventricular-myocytes
#8
Bojjibabu Chidipi, Min-Jeong Son, Joon-Chul Kim, Jeong Hyun Lee, Tran Quoc Toan, Nguyen Manh Cuong, Byung Ho Lee, Sun-Hee Woo
We previously reported that murrayafoline-A (1-methoxy-3-methyl-9H-carbazole, Mu-A) increases the contractility of ventricular myocytes, in part, via enhancing Ca(2+) influx through L-type Ca(2+) channels, and that it increases the Ca(2+) transients by activation of protein kinase C (PKC). In the present study, we further examined the cellular mechanisms for the enhancement of contractility and L-type Ca(2+) current (ICa,L) by Mu-A. Cell shortening and ICa,L were measured in rat ventricular myocytes using a video edge detection method and perforated patch-clamp technique, respectively...
August 5, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27074616/proinflammatory-cytokines-regulate-cementogenic-differentiation-of-periodontal-ligament-cells-by-wnt-ca-2-signaling-pathway
#9
Pingping Han, Tain Lloyd, Zetao Chen, Yin Xiao
Periodontal inflammation can inhibit cell differentiation of periodontal ligament cells (PDLCs), resulting in decreased bone/cementum regeneration ability. The Wnt signaling pathway, including canonical Wnt/β-catenin signaling and noncanonical Wnt/Ca(2+) signaling, plays essential roles in cell proliferation and differentiation during tooth development. However, little is still known whether noncanonical Wnt/Ca(2+) signaling cascade could regulate cementogenic/osteogenic differentiation capability of PDLCs within an inflammatory environment...
May 2016: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/26923100/involvement-of-calcium-calmodulin-dependent-protein-kinase-ii-in-methamphetamine-induced-neural-damage
#10
Xufeng Chen, Jingjing Xing, Lei Jiang, Wenyi Qian, Yixin Wang, Hao Sun, Yu Wang, Hang Xiao, Jun Wang, Jinsong Zhang
Methamphetamine (METH), an illicit drug, is widely abused in many parts of the world. Mounting evidence shows that METH exposure contributes to neurotoxicity, particularly for the monoaminergic neurons. However, to date, only a few studies have tried to unravel the mechanisms involved in METH-induced non-monoaminergic neural damage. Therefore, in the present study, we tried to explore the mechanisms for METH-induced neural damage in cortical neurons. Our results showed that METH significantly increased intracellular [Ca(2) (+) ]i in Ca(2) (+) -containing solution rather than Ca(2) (+) -free solution...
November 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/26901291/jujuboside-b-reduces-vascular-tension-by-increasing-ca2-influx-and-activating-endothelial-nitric-oxide-synthase
#11
Yixiu Zhao, Xin Zhang, Jiannan Li, Yu Bian, Miaomiao Sheng, Bin Liu, Zidong Fu, Yan Zhang, Baofeng Yang
Jujuboside B has been reported to have protective effect on many cardiovascular diseases. However, the effects of Jujuboside B on vascular tension and endothelial function are unknown. The present study investigated the effects of Jujuboside B on reducing vascular tension, protecting endothelial function and the potential mechanisms. The tension of isolated rat thoracic aorta ring was measured by Wire myograph system. The concentration of nitric oxide (NO) and the activity of endothelial nitric oxide synthase (eNOS) in human aortic endothelial cells (HAECs) were determined by Griess reagent method and enzyme-linked immune sorbent assay...
2016: PloS One
https://www.readbyqxmd.com/read/26859572/crosstalk-between-ca2-signaling-and-mitochondrial-h2o2-is-required-for-rotenone-inhibition-of-mtor-signaling-pathway-leading-to-neuronal-apoptosis
#12
Chunxiao Liu, Yangjing Ye, Qian Zhou, Ruijie Zhang, Hai Zhang, Wen Liu, Chong Xu, Lei Liu, Shile Huang, Long Chen
Rotenone, a neurotoxic pesticide, induces loss of dopaminergic neurons related to Parkinson's disease. Previous studies have shown that rotenone induces neuronal apoptosis partly by triggering hydrogen peroxide (H2O2)-dependent suppression of mTOR pathway. However, the underlying mechanism is not fully understood. Here, we show that rotenone elevates intracellular free calcium ion ([Ca2+]i) level, and activates CaMKII, resulting in inhibition of mTOR signaling and induction of neuronal apoptosis. Chelating [Ca2+]i with BAPTA/AM, preventing extracellular Ca2+ influx using EGTA, inhibiting CaMKII with KN93, or silencing CaMKII significantly attenuated rotenone-induced H2O2 production, mTOR inhibition, and cell death...
February 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/26722464/phosphorylated-neuronal-nitric-oxide-synthase-in-neuropathic-pain-in-rats
#13
Zhidong Zhou, Yingping Liang, Fumou Deng, Yong Cheng, Jing Sun, Lian Guo, Guohai Xu
Neuropathic pain caused by nervous system damage or system dysfunction. The pathogenesis and the mechanism underlying neuropathic pain remains unclear. The only known neurobiological component involved in the neuropathic pain is nitric oxide (NO). NO is synthesized by nitric oxide synthase (nNOS) from L-arginine and oxygen. nNOS is involved in the inflammatory pain and neuropathic pain. In this study, we aimed to identify whether KN93 reduced the pain in the rats. Sixty adult male SD rat were randomly divided into 4 groups...
2015: International Journal of Clinical and Experimental Pathology
https://www.readbyqxmd.com/read/26710089/camkii-activity-is-required-for-maintaining-learning-induced-enhancement-of-ampar-mediated-synaptic-excitation
#14
Sourav Ghosh, Iris Reuveni, Edi Barkai, Raphael Lamprecht
Learning leads to changes in AMPA receptor (AMPAR)-mediated synaptic excitation. The mechanisms for maintaining such alterations needed for memory persistence remain to be clarified. Here we report a novel molecular mechanism for maintaining learning-induced AMPAR-mediated enhancement of synaptic excitation. We show that training rats in a complex olfactory discrimination task, such that requires rule learning, leads to the enhancement of averaged amplitude of AMPAR-mediated miniature excitatory post-synaptic currents (mEPSCs) in piriform cortex pyramidal neurons for days after learning...
December 28, 2015: Journal of Neurochemistry
https://www.readbyqxmd.com/read/26631534/thapsigargin-induced-activation-of-ca-2-camkii-erk-in-brainstem-contributes-to-substance-p-release-and-induction-of-emesis-in-the-least-shrew
#15
Weixia Zhong, Seetha Chebolu, Nissar A Darmani
Cytoplasmic calcium (Ca(2+)) mobilization has been proposed to be an important factor in the induction of emesis. The selective sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA) inhibitor thapsigargin, is known to deplete intracellular Ca(2+) stores, which consequently evokes extracellular Ca(2+) entry through cell membrane-associated channels, accompanied by a prominent rise in cytosolic Ca(2+). A pro-drug form of thapsigargin is currently under clinical trial as a targeted cancer chemotherapeutic. We envisioned that the intracellular effects of thapsigargin could cause emesis and planned to investigate its mechanisms of emetic action...
April 2016: Neuropharmacology
https://www.readbyqxmd.com/read/26561550/cutting-edge-nanogel-based-delivery-of-an-inhibitor-of-camk4-to-cd4-t-cells-suppresses-experimental-autoimmune-encephalomyelitis-and-lupus-like-disease-in-mice
#16
Kotaro Otomo, Tomohiro Koga, Masayuki Mizui, Nobuya Yoshida, Christina Kriegel, Sean Bickerton, Tarek M Fahmy, George C Tsokos
Treatment of autoimmune diseases is still largely based on the use of systemically acting immunosuppressive drugs, which invariably cause severe side effects. Calcium/calmodulin-dependent protein kinase IV is involved in the suppression of IL-2 and the production of IL-17. Its pharmacologic or genetic inhibition limits autoimmune disease in mice. In this study, we demonstrate that KN93, a small-molecule inhibitor of calcium/calmodulin-dependent protein kinase IV, targeted to CD4(+) T cells via a nanolipogel delivery system, markedly reduced experimental autoimmune encephalomyelitis and was 10-fold more potent than the free systemically delivered drug in the lupus mouse models...
December 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/26498939/short-and-long-term-inhibition-of-cardiac-inward-rectifier-potassium-channel-current-by-an-antiarrhythmic-drug-bepridil
#17
Fangfang Ma, Hiroki Takanari, Kimiko Masuda, Masaki Morishima, Katsushige Ono
Bepridil is an effective antiarrhythmic drug on supraventricular and ventricular arrhythmias, and inhibitor of calmodulin. Recent investigations have been elucidating that bepridil exerts antiarrhythmic effects through its acute and chronic application for patients. The aim of this study was to identify the efficacy and the potential mechanism of bepridil on the inward-rectifier potassium channel in neonatal rat cardiomyocytes in acute- and long-term conditions. Bepridil inhibited inward-rectifier potassium current (I K1) as a short-term effect with IC50 of 17 μM...
July 2016: Heart and Vessels
https://www.readbyqxmd.com/read/26478783/cell-based-inhibitor-screening-identifies-multiple-protein-kinases-important-for-circadian-clock-oscillations
#18
Naohiro Kon, Yasunori Sugiyama, Hikari Yoshitane, Isamu Kameshita, Yoshitaka Fukada
Molecular oscillation of the circadian clock is based on E-box-mediated transcriptional feedback loop formed with clock genes and their encoding products, clock proteins. The clock proteins are regulated by post-translational modifications such as phosphorylation. We investigated the effects of a series of kinase inhibitors on gene expression rhythms in Rat-1 fibroblasts. The period of the cellular circadian rhythm in culture was lengthened by treatment with SB203580 (p38 MAPK inhibitor), SP600125 (JNK inhibitor), IC261 (CKI inhibitor) and Roscovitine (CDK inhibitor)...
July 2015: Communicative & Integrative Biology
https://www.readbyqxmd.com/read/26463508/kn-93-inhibits-ikr-in-mammalian-cardiomyocytes
#19
Bence Hegyi, Ye Chen-Izu, Zhong Jian, Rafael Shimkunas, Leighton T Izu, Tamas Banyasz
Calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitor KN-93 is widely used in multiple fields of cardiac research especially for studying the mechanisms of cardiomyopathy and cardiac arrhythmias. Whereas KN-93 is a potent inhibitor of CaMKII, several off-target effects have also been found in expression cell systems and smooth muscle cells, but there is no information on the KN93 side effects in mammalian ventricular myocytes. In this study we explore the effect of KN-93 on the rapid component of delayed rectifier potassium current (IKr) in the ventricular myocytes from rabbit and guinea pig hearts...
December 2015: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/26277509/-role-of-calmodulin-dependent-protein-kinase-ii-in-bupivacaine-hydrochloride-induced-injury-of-sh-sy5y-cells
#20
Xianjie Wen, Jiying Zhong, Tao Zhang, Xiaohong Lai, Hongzhen Liu, Hanbing Wang, Chengxiang Yang
OBJECTIVE: To investigate the effect of KN93, a calmodulin-dependent protein kinase II (CaMK II) inhibitor, on SH-SY5Y cell injury induced by bupivacaine hydrochloride. METHODS: SH-SY5Y cells exposed for 24 h to 1 mmol/L KN93, 1 mmol/L bupivacaine hydrochloride, or both were examined for morphological changes and Cav3.1 protein expressions using Western blotting. The vitality and apoptosis rate of the cells at different time points during the exposures were assessed with MTT assay and flow cytometry, respectively...
August 2015: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
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