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https://www.readbyqxmd.com/read/29244485/critical-role-of-trp-588-of-presynaptic-munc13-1-for-ligand-binding-and-membrane-translocation
#1
Joydip Das, Noemi Kedei, Jessica S Kelsey, Youngki You, Satyabrata Pany, Gary A Mitchell, Nancy E Lewin, Peter M Blumberg
Munc13-1 is a presynaptic active-zone protein essential for neurotransmitter release and presynaptic plasticity in the brain. This multi-domain scaffold protein contains a C1 domain that binds to the activator diacylglycerol/phorbol ester. Although the C1 domain bears close structural homology with the C1 domains of protein kinase C (PKC), the tryptophan residue at position 22 (588 in the full-length Munc13-1) occludes the activator binding pocket, which is not the case for PKC. To elucidate the role of this tryptophan, we generated W22A, W22K, W22D, W22Y and W22F substitutions in the full-length Munc13-1, expressed the GFP- tagged constructs in Neuro-2a cells, and measured their membrane translocation in response to phorbol ester treatment by imaging of the live cells using confocal microscopy...
December 15, 2017: Biochemistry
https://www.readbyqxmd.com/read/29243851/alterations-in-gene-expression-in-vitamin-d-deficiency-down-regulation-of-liver-cyp7a1-and-renal-oat3-in-mice
#2
Holly P Quach, Keumhan Noh, Stacie Y Hoi, Adrie Bruinsma, Geny M M Groothuis, Albert P Li, Edwin C Y Chow, K Sandy Pang
The vitamin D-deficient model, established in C57BL/6 mouse after 8-week feeding of vitamin D-deficient diets in absence or presence of added calcium, was found associated with elevated levels of plasma parathyroid hormone (PTH) and plasma and liver cholesterol, and reduction in cholesterol 7α-hydroxylase (Cyp7a1, rate-limiting enzyme for cholesterol metabolism) and renal Oat3 mRNA/protein expression levels. There was, however, no change in plasma calcium and phosphate levels. Appraisal of the liver revealed up-regulation of mRNA expressions of the small heterodimer partner (Shp) and attenuation of Cyp7a1, which contributed to hypercholesterolemia in vitamin D-deficiency...
December 15, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/29242118/activation-of-transglutaminase-2-by-nerve-growth-factor-in-differentiating-neuroblastoma-cells-a-role-in-cell-survival-and-neurite-outgrowth
#3
Alanood S Algarni, Alan J Hargreaves, John M Dickenson
NGF (nerve growth factor) and tissue transglutaminase (TG2) play important roles in neurite outgrowth and modulation of neuronal cell survival. In this study, we investigated the regulation of TG2 transamidase activity by NGF in retinoic acid-induced differentiating mouse N2a and human SH-SY5Y neuroblastoma cells. TG2 transamidase activity was determined using an amine incorporation and a peptide cross linking assay. In situ TG2 activity was assessed by visualising the incorporation of biotin-X-cadaverine using confocal microscopy...
December 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29234372/hawthorn-leaf-flavonoids-protect-against-diabetes-induced-cardiomyopathy-in-rats-via-pkc-%C3%AE-signaling-pathway
#4
Qing Min, Yuting Bai, Yuchen Zhang, Wei Yu, Minli Zhang, Dongyang Liu, Tingting Diao, Wei Lv
Objectives: DCM has become one of the main reasons of death in diabetic patients. In this study, we aimed to explore the hawthorn leaf flavonoids (HLF) protective effect against diabetes-induced cardiac injury and the underlying mechanisms in experimental rats. Methods: Experimental diabetic model was induced by intraperitoneal injection of streptozotocin (STZ, 40 mg/kg) in rats after feeding with high-fat diet for 8 weeks. The diabetic rats received a 16-week treatment of different doses of HLF (50, 100, and 200)...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29233660/negative-inotropic-effects-of-diadenosine-tetraphosphate-are-mediated-by-protein-kinase-c-and-phosphodiesterases-stimulation-in-the-rat-heart
#5
Nikolai Pakhomov, Ksenia Pustovit, Victoria Potekhina, Tatiana Filatova, Vladislav Kuzmin, Denis Abramochkin
Extracellular diadenosine polyphosphates (ApnA) are recently considered as an endogenous signaling compounds with transmitter-like activity which present in numerous tissues, including heart. It has been demonstrated previously that extracellular ApnA cause alteration of the heart functioning via purine receptors in different mammalian species. Nevertheless, principal intracellular pathways which underlie ApnA action in the heart remain unknown. In the present study the role of the P2Y-associated intracellular regulatory pathway in the mediation of diadenosine tetraphosphate (Ap4A) effects in the rat heart has been investigated for the first time...
December 9, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29233519/inhibition-of-central-de-novo-ceramide-synthesis-restores-insulin-signaling-in-hypothalamus-and-enhances-%C3%AE-cell-function-of-obese-zucker-rats
#6
Mélanie Campana, Lara Bellini, Claude Rouch, Latif Rachdi, Nicolas Coant, Noémie Butin, Cécile L Bandet, Erwann Philippe, Kelly Meneyrol, Nadim Kassis, Julien Dairou, Eric Hajduch, Benoit Colsch, Christophe Magnan, Hervé Le Stunff
OBJECTIVES: Hypothalamic lipotoxicity has been shown to induce central insulin resistance and dysregulation of glucose homeostasis; nevertheless, elucidation of the regulatory mechanisms remains incomplete. Here, we aimed to determine the role of de novo ceramide synthesis in hypothalamus on the onset of central insulin resistance and the dysregulation of glucose homeostasis induced by obesity. METHODS: Hypothalamic GT1-7 neuronal cells were treated with palmitate...
November 7, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29233021/amitriptyline-modulated-ca2-signaling-and-induced-ca2-independent-cell-viability-in-human-osteosarcoma-cells
#7
T Lu, C-T Chou, W-Z Liang, C-C Kuo, I-L Chen, J-L Wang, C-R Jan
Amitriptyline is a widely used tricyclic antidepressant, which acts primarily as a serotonin-norepinephrine reuptake inhibitor. This study examined the effect of amitriptyline on Ca2+ homeostasis and its related mechanism in MG63 human osteosarcoma cells. Amitriptyline evoked cytosolic-free Ca2+ concentrations ([Ca2+]i) rises concentration dependently. Amitriptyline-evoked Ca2+ entry was confirmed by Mn2+-induced quench of fura-2 fluorescence. This entry was inhibited by Ca2+ entry modulators nifedipine, econazole, SKF96365, the protein kinase C (PKC) activator phorbol 12-myristate 13 acetate but was not affected by the PKC inhibitor GF109203X...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29231479/-effects-of-electroacupuncture-preconditioning-on-expression-of-aquaporin-1-and-activity-of-protein-kinase-c-in-myocardium-of-rats-with-acute-myocardial-ischemia-reperfusion-injury
#8
Ronglin Cai, Ling Hu, Guoming Shen, Qing Yu, Jie Wang, Zijian Wu, Meng Li
OBJECTIVE: To explore the partial action mechanism and the myocardial protective effect differences between electroacupuncture (EA) preconditioning at "Neiguan"(PC 6) and "Taiyuan"(LU 9) in rats with acute myocardial ischemia-reperfusion injury. METHODS: Ninety-six Wistar rats were randomly assigned into a sham-operation group, a model group, a Neiguan group and a Taiyuan group, 24 rats in each one. The rats in the Neiguan group and Taiyuan group were treated with EA (2 Hz in frequency, 1 mA in intensity) at "Neiguan" (PC 6) and "Taiyuan" (LU 9) respectively, 20 min per treatment, once a day for consecutive 7 days...
February 12, 2017: Zhongguo Zhen Jiu, Chinese Acupuncture & Moxibustion
https://www.readbyqxmd.com/read/29230399/role-of-protein-kinase-c-in-bipolar-disorder-a-review-of-the-current-literature
#9
REVIEW
Ashwini Saxena, Giselli Scaini, Daniela V Bavaresco, Camila Leite, Samira S Valvassoria, André F Carvalho, João Quevedo
Bipolar disorder (BD) is a major health problem. It causes significant morbidity and imposes a burden on the society. Available treatments help a substantial proportion of patients but are not beneficial for an estimated 40-50%. Thus, there is a great need to further our understanding the pathophysiology of BD to identify new therapeutic avenues. The preponderance of evidence pointed towards a role of protein kinase C (PKC) in BD. We reviewed the literature pertinent to the role of PKC in BD. We present recent advances from preclinical and clinical studies that further support the role of PKC...
November 2017: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/29230097/the-molecular-mechanisms-of-regulation-on-usp2-s-alternative-splicing-and-the-significance-of-its-products
#10
REVIEW
Han-Qing Zhu, Feng-Hou Gao
Ubiquitin-specific protease 2 (USP2) has a regulatory function in cell growth or death and is involved in the pathogenesis of various diseases. USP2 gene can generate 7 splicing variants through alternative splicing, and 5 variants respectively as USP2-201, USP2-202, USP2-204, USP2-205, USP2-206 can encode proteins. The influence of circadian rhythm, nutrition and androgen on specific signaling molecules or cytokines can regulate the alternative splicing of USP2. Specifically, PKC activator, IL-1β, TNF-α, PDGF-BB, TGF-β1 are all regulatory factors for USP2's alternative splicing...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/29229703/orai1-plays-a-crucial-role-in-central-sensitization-by-modulating-neuronal-excitability
#11
Yannong Dou, Jingsheng Xia, Ruby Gao, Xinghua Gao, Frances M Munoz, Dongyu Wei, Yuzhen Tian, James E Barrett, Seena Ajit, Olimpia Meucci, James W Putney, Yue Dai, Huijuan Hu
Pathological pain is a common and debilitating condition that is often poorly managed. Central sensitization is an important mechanism underlying pathological pain. However, candidate molecules involved in central sensitization remain unclear. Store-operated calcium channels (SOCs) mediate important calcium signals in non-excitable and excitable cells. SOCs have been implicated in a wide variety of human pathophysiological conditions including immunodeficiency, occlusive vascular diseases and cancer. However, the role of SOCs in central nervous system (CNS) disorders has been relatively unexplored...
December 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29229685/the-essential-role-of-phospho-t38-cpi-17-in-the-maintenance-of-physiological-blood-pressure-using-genetically-modified-mice
#12
Qunhui Yang, Wataru Fujii, Noriyuki Kaji, Shigeru Kakuta, Kodai Kada, Masayoshi Kuwahara, Hirokazu Tsubone, Hiroshi Ozaki, Masatoshi Hori
PKC-potentiated phosphorylation-dependent inhibitory protein of protein phosphatase 1 (CPI-17), an endogenous myosin phosphatase inhibitory protein, is considered a key molecule for Ca2+ sensitization of the contractile apparatus. Here, we have used clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 to generate CPI-17-deficient [knockout (KO)] and threonine 38 (T38)-phospho-resistant mice [Threonine mutant into Alanine (TA)], and then effects of CPI-17 on vascular contractility in vitro and mean blood pressure (MBP) in vivo were investigated...
December 11, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29227555/combining-fluorescence-and-bioluminescence-microscopy-to-study-the-series-of-events-from-cellular-signal-transduction-to-gene-expression
#13
Kazuhito Goda, Takeo Takahashi, Hirobumi Suzuki
The molecular interactions and translocation of signal transduction factors in individual cells can be imaged by fluorescence microscopy. Alternatively, downstream promoter activity in single cells can be imaged by bioluminescence microscopy. However, the same stimuli can lead to different gene expression responses in individual cells. For this reason, it is desirable to simultaneously image signal transduction and gene expression events in the same cells. Here, we describe a method that combines fluorescence and bioluminescence microscopy to image protein kinase C (PKC) translocation from the cytosol to the plasma membrane and the expression of nuclear factor kappa-light polypeptide B (NF-κB)-regulated genes...
December 11, 2017: Current Protocols in Cell Biology
https://www.readbyqxmd.com/read/29223917/molecular-dynamics-simulations-suggest-changes-in-electrostatic-interactions-as-a-potential-mechanism-through-which-serine-phosphorylation-inhibits-dna-polymerase-%C3%AE-s-activity
#14
Dirar Homouz, Kwee Hong Joyce-Tan, Mohd Shahir Shamsir, Ibrahim M Moustafa, Haitham Idriss
DNA polymerase β is a 39kDa enzyme that is a major component of Base Excision Repair in human cells. The enzyme comprises two major domains, a 31kDa domain responsible for the polymerase activity and an 8kDa domain, which bind ssDNA and has a deoxyribose phosphate (dRP) lyase activity. DNA polymerase β was shown to be phosphorylated in vitro with protein kinase C (PKC) at serines 44 and 55 (S44 and S55), resulting in loss of its polymerase enzymic activity, but not its ability to bind ssDNA. In this study, we investigate the potential phosphorylation-induced structural changes for DNA polymerase β using molecular dynamics...
November 7, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29220720/induction-of-thymic-stromal-lymphopoietin-by-a-steroid-alkaloid-derivative-in-mouse-keratinocytes
#15
Yan Weng, Natsumi Mizuno, Jiangxu Dong, Ryosuke Segawa, Takayuki Yonezawa, Byung Yoon Cha, Je-Tae Woo, Takahiro Moriya, Masahiro Hiratsuka, Noriyasu Hirasawa
Thymic stromal lymphopoietin (TSLP) plays critical roles in inducing and exacerbating allergic diseases. Chemical compounds that induce TSLP production can enhance sensitization to antigens and exacerbate allergic inflammation. Hence, identifying such chemicals will be important to prevent an increase in allergic diseases. In the present study, we found, for the first time, that a steroid alkaloid derivative, code no. 02F04, concentration and time dependently induced mRNA expression and production of TSLP in a mouse keratinocyte cell line, PAM212...
December 5, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29219195/dissecting-the-17%C3%AE-estradiol-pathways-necessary-for-neuroglobin-anti-apoptotic-activity-in-breast-cancer
#16
Marco Fiocchetti, Manuela Cipolletti, Paolo Ascenzi, Maria Marino
Neuroglobin (NGB) is a relatively recent discovered monomeric heme-protein, which behave in neurons as a sensor of injuring stimuli including oxidative stress, hypoxia, and neurotoxicity. In addition, the anti-apoptotic activity of overexpressed NGB has been reported both in neurons and in cancer cell lines. We recently demonstrated that, NGB functions as a compensatory protein of the steroid hormone 17β-estradiol (E2) protecting cancer cells against the apoptotic death induced by oxidative stress. However, as far we known, the E2-induced signaling pathways at the root of NGB over-expression and mitochondrial re-localization in breast cancer cells is still elusive...
December 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29217666/epac1-regulates-endothelial-annexin-a2-cell-surface-translocation-and-plasminogen-activation
#17
Wenli Yang, Fang C Mei, Xiaodong Cheng
Annexins, a family of highly conserved calcium- and phospholipid-binding proteins, play important roles in a wide range of physiologic functions. Among the 12 known annexins in humans, annexin A2 (AnxA2) is one of the most extensively studied and has been implicated in various human diseases. AnxA2 can exist as a monomer or a heterotetrameric complex with S100A10 (P11) and plays a critical role in many cellular processes, including exocytosis, endocytosis, and membrane organization. At the endothelial cell surface, the (AnxA2·P11)2 tetramer-acting as a coreceptor for plasminogen and tissue plasminogen activator (tPA)-accelerates tPA-dependent activation of the fibrinolytic protease, plasmin, the enzyme that is responsible for thrombus dissolution and the degradation of fibrin...
December 7, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29216442/lycopene-depresses-glutamate-release-through-inhibition-of-voltage-dependent-ca-sup-2-sup-entry-and-protein-kinase-c-in-rat-cerebrocortical-nerve-terminals
#18
Cheng-Wei Lu, Chi-Feng Hung, Wei-Horng Jean, Tzu-Yu Lin, Shu-Kuei Huang, Su Jane Wang
Lycopene is a natural dietary carotenoid which was reported to exhibit neuroprotective profile. Considering that excitotoxicity and cell death induced by glutamate are involved in many brain disorders, the effect of lycopene on glutamate release in rat cerebrocortical nerve terminals and the possible mechanism involved in such effect was investigated. We observed here that lycopene inhibited 4-aminopyridine (4-AP)-evoked glutamate release and intrasynaptosomal Ca <sup>2+<sup> concentration elevation...
December 7, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/29212172/safflor-yellow-b-reduces-hypoxia-mediated-vasoconstriction-by-regulating-endothelial-micro-ribonucleic-acid-nitric-oxide-synthase-signaling
#19
Chaoyun Wang, Ying Yang, Miao Li, Xin Liu, Qiaoyun Wang, Wenyu Xin, Hongliu Sun, Qingyin Zheng
Hypoxia-induced generation of vasoconstrictors reduces cerebral blood flow (CBF) while nitric oxide (NO) synthase (NOS) and microRNAs (miRNA) in endothelial cells (ECs) suppress vasoconstriction. Safflor yellow B (SYB), a natural plant compound, previously attenuated angiotensin II-mediated injury of ECs and maintained endothelial function. This study investigated the putative involvement of NOS and miRNAs in SYB-mediated resistance to hypoxia-induced vasoconstriction. In vivo, chronic hypoxia was induced in rats, and SYB was administered intravenously...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29209553/antidyskinetic-treatment-with-mtep-affects-multiple-molecular-pathways-in-the-parkinsonian-striatum
#20
Jing-Ya Lin, Zhen-Guo Liu, Cheng-Long Xie, Lu Song, Ai-Juan Yan
Parkinson's disease is characterized by dopaminergic neuron loss and dopamine (DA) depletion in the striatum. Standard treatment is still focused on the restoration of dopamine with exogenous L-Dopa, which however causes L-Dopa-induced dyskinesia (LID). Several studies have shown that antagonism of the metabotropic glutamate receptor 5 alleviates LID, but the underlying mechanisms have remained unclear. We set out to determine where this alleviation may depend on restoring the equilibrium between the two main striatofugal pathways...
2017: Parkinson's Disease
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