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https://www.readbyqxmd.com/read/29452158/protein-kinase-c-epsilon-mediates-the-inhibition-of-angiotensin-ii-on-the-slowly-activating-delayed-rectifier-potassium-current-through-channel-phosphorylation
#1
Xiangbo Gou, Wenying Wang, Sihao Zou, Yajuan Qi, Yanfang Xu
The slowly activating delayed rectifier K + current (I Ks ) is one of the main repolarizing currents in the human heart. Evidence has shown that angiotensin II (Ang II) regulates I Ks through the protein kinase C (PKC) pathway, but the related results are controversial. This study was designed to identify PKC isoenzymes involved in the regulation of I Ks by Ang II and the underlying molecular mechanism. The whole-cell patch-clamp technique was used to record I Ks in isolated guinea pig ventricular cardiomyocytes and in human embryonic kidney (HEK) 293 cells co-transfected with human KCNQ1/KCNE1 genes and Ang II type 1 receptor genes...
February 13, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29452119/mirs-103-107-regulate-autophagy-in-the-epidermis
#2
Sijia Wang, Aya Kobeissi, Ying Dong, Nihal Kaplan, Wending Yang, Congcong He, Kang Zeng, Han Peng
We have shown that microRNAs-103 and -107(miRs-103/107) positively regulate end-stage autophagy via ensuring dynamin activity in cultured keratinocytes. Most work in end-stage autophagy has been conducted using in vitro model systems. In vivo regulation of end-stage autophagy in epidermis remains unknown. Here, we used antagomirs to subcutaneously knock-down miR-107 in the skin; conversely, we delivered miR-107 mimic subcutaneously via in vivo transfection to increase this miRNA. We found that antagomir-107 treatment in epidermis: (i) depleted endogenous miR-107; (ii) increased GFP-LC3 puncta in epidermal basal layers of GFP-LC3 transgenic mice, indicative of an accumulation of autophagosomes; (iii) inhibited LC3 turnover and increased p62, suggesting an inhibition of autophagy flux; and (iv) increased phosphorylated dynamin (p-dynamin, an inactive form), a key enzyme in end-stage autophagy...
February 13, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29452094/evolving-mechanisms-of-vascular-smooth-muscle-contraction-highlight-key-targets-in-vascular-disease
#3
REVIEW
Zhongwei Liu, Raouf A Khalil
Vascular smooth muscle (VSM) plays an important role in the regulation of vascular function. Identifying the mechanisms of VSM contraction has been a major research goal in order to determine the causes of vascular dysfunction and exaggerated vasoconstriction in vascular disease. Major discoveries over several decades have helped to better understand the mechanisms of VSM contraction. Ca 2+ has been established as a major regulator of VSM contraction, and its sources, cytosolic levels, homeostatic mechanisms and subcellular distribution have been defined...
February 13, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29449846/pemphigus-a-disease-of-desmosome-dysfunction-caused-by-multiple-mechanisms
#4
Volker Spindler, Jens Waschke
Pemphigus is a severe autoimmune-blistering disease of the skin and mucous membranes caused by autoantibodies reducing desmosomal adhesion between epithelial cells. Autoantibodies against the desmosomal cadherins desmogleins (Dsgs) 1 and 3 as well as desmocollin 3 were shown to be pathogenic, whereas the role of other antibodies is unclear. Dsg3 interactions can be directly reduced by specific autoantibodies. Autoantibodies also alter the activity of signaling pathways, some of which regulate cell cohesion under baseline conditions and alter the turnover of desmosomal components...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29446730/salvaging-the-ischemic-heart-gi-coupled-receptors-in-mast-cells-activate-a-pkc%C3%AF-aldh2-pathway-providing-anti-ras-cardioprotection
#5
Alice Marino, Roberto Levi
BACKGROUND: Excessive norepinephrine (NE) release in the ischemic heart elicits severe and often lethal arrhythmias. Resident cardiac mast cells synthesize and store active renin, which is released upon degranulation, causing the activation of a local cardiac renin-angiotensin system (RAS) responsible for NE release and consequent arrhythmias. Toxic aldehydes, known to be formed by lipid peroxidation in ischemia/reperfusion (I/R), have been shown to degranulate mast cells and activate a local RAS...
February 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29445764/quantified-coexpression-analysis-of-central-amygdala-subpopulations
#6
Kenneth M McCullough, Filomene G Morrison, Jakob Hartmann, William A Carlezon, Kerry J Ressler
Molecular identification and characterization of fear controlling circuitries is a promising path towards developing targeted treatments of fear-related disorders. Three-color in situ hybridization analysis was used to determine whether somatostatin (SOM, Sst ), neurotensin (NTS, Nts ), corticotropin-releasing factor (CRF, Crf ), tachykinin 2 (TAC2, Tac2 ), protein kinase c-δ (PKC-δ, Prkcd ), and dopamine receptor 2 (DRD2, Drd2 ) mRNA colocalize in male mouse amygdala neurons. Expression and colocalization was examined across capsular (CeC), lateral (CeL), and medial (CeM) compartments of the central amygdala...
January 2018: ENeuro
https://www.readbyqxmd.com/read/29440456/specific-pkc-%C3%AE-ii-inhibitor-one-stone-two-birds-in-the-treatment-of-diabetic-foot-ulcers
#7
Sushant Kumar Das, Yi Feng Yuan, Mao Quan Li
Purpose: To explore whether or not inhibition of protein kinase C beta II (PKC βII) stimulates angiogenesis as well as prevents excessive NETosis in diabetics thus accelerating wound healing. Material and methods: Streptozotocin (STZ, 60 mg/kg/d × 5 d, i.p.) was injected to induce Type I Diabetes in male ICR mice. Mice were treated with Ruboxistaurin (30 mg/kg/d, orally) for 14 consecutive days. Wound closure was evaluated by wound area and number of CD31 stained capillaries. Flow cytometry was done to evaluate number of circulating endothelial progenitor cells (EPCs)...
February 12, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29439248/transient-receptor-potential-vanilloid-4-activation-induced-increase-in-glycine-activated-current-in-mouse-hippocampal-pyramidal-neurons
#8
Mengwen Qi, Chunfeng Wu, Zhouqing Wang, Li Zhou, Chen Men, Yimei Du, Songming Huang, Lei Chen, Ling Chen
BACKGROUND/AIMS: Glycine plays an important role in regulating hippocampal inhibitory/ excitatory neurotransmission through activating glycine receptors (GlyRs) and acting as a co-agonist of N-methyl-d-aspartate-type glutamate receptors. Activation of transient receptor potential vanilloid 4 (TRPV4) is reported to inhibit hippocampal A-type γ-aminobutyric acid receptor, a ligand-gated chloride ion channel. GlyRs are also ligand-gated chloride ion channels and this paper aimed to explore whether activation of TRPV4 could modulate GlyRs...
February 7, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29438777/the-differential-roles-of-pea15-phosphorylations-in-reactive-astrogliosis-and-astroglial-apoptosis-following-status-epilepticus
#9
Jin-Young Park, Tae-Cheon Kang
Up to this day, the roles of PEA15 expression and its phosphorylation in seizure-related events have not been still unclear. In the present study, we found that PEA15 was distinctly phosphorylated in reactive astrocytes and apoptotic astrocytes in the rat hippocampus following LiCl-pilocarpine-induced status epilepticus (SE, a prolonged seizure activity). PEA15-serine (S) 104 phosphorylation was up-regulated in reactive astrocytes following SE, although PEA15 expression and its S116 phosphorylation were unaltered...
February 10, 2018: Neuroscience Research
https://www.readbyqxmd.com/read/29436640/-corrigendum-roles-and-mechanisms-of-trpc3-and-the-plc%C3%AE-pkc-cpi-17-signaling-pathway-in-regulating-parturition
#10
Jing Chen, Dongming Zheng, Hong Cui, Sishi Liu, Lijuan Zhang, Caixia Liu
Subsequent to the publication of the above paper, the authors have realized that there were errors in Fig. 1 on page 902; essentially, the experimental data described as being 'Preterm' and 'Infected preterm' should have been labelled as 'Full‑term without labor' and 'Preterm', respectively. Note that these errors in Fig. 1 were not reflected in the published figure legend. The corrected version of Fig. 1 is shown here. The authors sincerely apologize for this mistake, and regret any inconvenience this mistake has caused...
February 7, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29436605/novel-iridium-iii-%C3%A2-derived-organometallic-compound-for-the-inhibition-of-human-platelet-activation
#11
Kou-Gi Shyu, Marappan Velusamy, Chih-Wei Hsia, Chih-Hao Yang, Chih-Hsuan Hsia, Duen-Suey Chou, Thanasekaran Jayakumar, Joen-Rong Sheu, Jiun-Yi Li
Since cisplatin achieved clinical success, transition metal platinum (Pt) drugs have been effectively used for the treatment of cancer. Iridium (Ir) compounds are considered to be potential alternatives to Pt compounds, as they possess promising anticancer effects with minor side effects. Platelet activation is associated with the metastasis and progression of cancer, and also with arterial thrombosis. Therefore, it is necessary to develop novel, effective antithrombotic agents. An Ir (III)‑derived complex, [Ir (Cp*) 1‑(2‑pyridyl)‑3‑(3‑methoxyphenyl)imidazo[1,5‑a]pyridine Cl]BF4 (Ir‑3), was developed as a novel antiplatelet drug...
February 7, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29436118/cortistatin%C3%A2-inhibits%C3%A2-arterial%C3%A2-calcification%C3%A2-in%C3%A2-rats%C3%A2-via%C3%A2-gsk3%C3%AE-%C3%AE-catenin%C3%A2-and%C3%A2-pkc%C3%A2-signaling%C3%A2-but%C3%A2-not%C3%A2-jnk%C3%A2-signaling
#12
Yue Liu, Fang Lin, Yu Fu, Wenjia Chen, Wenxiu Liu, Jinyu Chi, Xiaohui Zhang, Xinhua Yin
AIM: Cortistatin (CST) is a newly discovered endogenous active peptide that exerts protective effects on the cardiovascular system. However, the relationship between CST and aortic calcification and the underlying mechanism remain obscure. Therefore, we investigated effects of CST on aortic calcification and its signaling pathways. METHODS: Calcium content and alkaline phosphatase (ALP) activity were measured using the o-cresolphthalein colorimetric method and ALP assay kit, respectively...
February 13, 2018: Acta Physiologica
https://www.readbyqxmd.com/read/29435596/ripk4-activity-in-keratinocytes-is-controlled-by-the-scf%C3%AE-trcp-ubiquitin-ligase-to-maintain-cortical-actin-organization
#13
Giel Tanghe, Corinne Urwyler-Rösselet, Philippe De Groote, Emmanuel Dejardin, Pieter-Jan De Bock, Kris Gevaert, Peter Vandenabeele, Wim Declercq
RIPK4 is a key player in epidermal differentiation and barrier formation. RIPK4 signaling pathways controlling keratinocyte proliferation and differentiation depend on its kinase activity leading to Dvl2, Pkp1 and IRF6 phosphorylation and NF-κB activation. However, the mechanism regulating RIPK4 activity levels remains elusive. We show that cultured keratinocytes display constitutive active phosphorylated RIPK4 while PKC signaling can trigger RIPK4 activation in various non-keratinocyte cell lines, in which RIPK4 is present in a non-phosphorylated state...
February 12, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29432553/short-term-heat-stress-altered-metabolism-and-insulin-signaling-in-skeletal-muscle
#14
Shanthi Ganesan, Corey M Summers, Sarah C Pearce, Nicholas K Gabler, Rudy J Valentine, Lance H Baumgard, Robert P Rhoads, Joshua T Selsby
Heat-related complications continue to be a major health concern for humans and animals and lead to potentially life-threatening conditions. Heat stress (HS) alters metabolic parameters and may alter glucose metabolism and insulin signaling. Therefore, the purpose of this investigation was to determine the extent to which 12 h of HS altered energetic metabolism in oxidative skeletal muscle. To address this, crossbred gilts (n=8/group) were assigned to one of three environmental treatments for 12 h: thermoneutral (TN; 21° C), heat stress (HS; 37° C), or pair-fed to HS counterparts but housed in TN conditions (PFTN)...
February 8, 2018: Journal of Animal Science
https://www.readbyqxmd.com/read/29432535/protein-kinase-c-activity-is-a-protective-modifier-of-purkinje-neuron-degeneration-in-cerebellar-ataxia
#15
Ravi Chopra, Aaron H Wasserman, Stefan M Pulst, Chris I De Zeeuw, Vikram G Shakkottai
Among the many types of neurons expressing protein kinase C (PKC) enzymes, cerebellar Purkinje neurons are particularly reliant on appropriate PKC activity for maintaining homeostasis. The importance of PKC enzymes in Purkinje neuron health is apparent as mutations in PRKCG (encoding PKCγ) cause cerebellar ataxia. PRKCG has also been identified as an important node in ataxia gene networks more broadly, but the functional role of PKC in other forms of ataxia remains unexplored, and the mechanisms by which PKC isozymes regulate Purkinje neuron health are not well understood...
February 8, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29432478/correction-apoptosis-by-pt-o-o-acac-%C3%AE-acac-dms-requires-pkc-%C3%AE-mediated-p53-activation-in-malignant-pleural-mesothelioma
#16
Antonella Muscella, Carla Vetrugno, Luca Giulio Cossa, Giovanna Antonaci, Amilcare Barca, Sandra Angelica De Pascali, Francesco Paolo Fanizzi, Santo Marsigliante
[This corrects the article DOI: 10.1371/journal.pone.0181114.].
2018: PloS One
https://www.readbyqxmd.com/read/29428611/high-level-expression-of-an-engineered-%C3%AE-mannanase-mrmman5a-in-pichia-pastoris-for-manno-oligosaccharide-production-using-steam-explosion-pretreated-palm-kernel-cake
#17
Yan-Xiao Li, Ping Yi, Jun Liu, Qiao-Juan Yan, Zheng-Qiang Jiang
An engineered β-mannanase (mRmMan5A) from Rhizomucor miehei was successfully expressed in Pichia pastoris. Through high cell density fermentation, the expression level of mRmMan5A reached 79,680 U mL-1. The mRmMan5A showed maximum activity at pH 4.5 and 65 °C, and exhibited high specific activities towards mannans. To produce manno-oligosaccharides, palm kernel cake (PKC) was pretreated by steam explosion at 200 °C for 7.5 min, and then hydrolyzed by mRmMan5A. As a result, the total manno-oligosaccharide yield reached 34...
February 1, 2018: Bioresource Technology
https://www.readbyqxmd.com/read/29428215/spinal-pkc-activation-induced-neuronal-hmgb1-translocation-contributes-to-hyperalgesia-in-a-bone-cancer-pain-model-in-rats
#18
Kang An, Hui Rong, Huadong Ni, Chunyan Zhu, Longsheng Xu, Qianying Liu, Yajing Chen, Ying Zheng, Bing Huang, Ming Yao
Bone cancer pain (BCP) remains a serious complication of malignancy, which is an intractable clinical problem due to the gap in knowledge of its underlying mechanisms. Recent studies have demonstrated that the major involvement of neuroinflammation, particularly high-mobility group box 1 (HMGB1), which was identified as a late mediator of inflammation, in a number of pain conditions. However, the underlying mechanisms and functions of HMGB1 release in spinal cord, and its contributions to the development of BCP as well, are poorly understood...
February 8, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29424951/synthesis-and-biological-evaluation-of-fluorescent-bryostatin-analogues
#19
Thomas J Cummins, Noemi Kedei, Agnes Czikora, Nancy E Lewin, Sharon Kirk, Mark E Petersen, Kevin M McGowan, Jin-Qiu Chen, Xiaoling Luo, Randall C Johnson, Sarangan Ravichandran, Peter M Blumberg, Gary E Keck
To investigate the cellular distribution of tumor-promoting vs nontumor-promoting bryostatin analogues, we synthesized fluorescently labeled variants of two bryostatin derivatives that have previously shown either phorbol ester-like or bryostatin-like biological activity on U937 cells. These new fluorescent analogues both displayed high affinity for PKC binding and retained the basic properties of the parent, unlabeled compounds in U937 assays. The fluorescent compounds showed similar patterns of intracellular distribution in cells, however, arguing against an existing hypothesis that varying patterns of intracellular distribution contributed to the difference in biological activity...
February 9, 2018: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29416015/multiple-molecular-mechanisms-form-a-positive-feedback-loop-driving-amyloid-%C3%AE-42-peptide-induced-neurotoxicity-via-activation-of-the-trpm2-channel-in-hippocampal-neurons
#20
Xin Li, Lin-Hua Jiang
Emerging evidence supports an important role for the ROS-sensitive TRPM2 channel in mediating age-related cognitive impairment in Alzheimer's disease (AD), particularly neurotoxicity resulting from generation of excessive neurotoxic Aβ peptides. Here we examined the elusive mechanisms by which Aβ42 activates the TRPM2 channel to induce neurotoxicity in mouse hippocampal neurons. Aβ42-induced neurotoxicity was ablated by genetic knockout (TRPM2-KO) and attenuated by inhibition of the TRPM2 channel activity or activation through PARP-1...
February 7, 2018: Cell Death & Disease
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