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https://www.readbyqxmd.com/read/28742858/reduction-of-endoplasmic-reticulum-mitochondria-interactions-in-beta-cells-from-patients-with-type-2-diabetes
#1
Charles Thivolet, Guillaume Vial, Romeo Cassel, Jennifer Rieusset, Anne-Marie Madec
Type 2 diabetes develops when beta cells are not able to fulfill insulin needs. The role of the endoplasmic reticulum-mitochondria junction in coordinating the functions of these two organelles throughout the natural history of type 2 diabetes is determinant and may explain the alterations of insulin biosynthesis. Our goal was to study endoplasmic reticulum and mitochondrial interactions in human beta cells from organ donors with type 2 diabetes. Pancreas samples were obtained via the network for pancreatic organ donors with diabetes (nPOD) based on disease status with 12 subjects with type 2 diabetes and 9 non-diabetic controls...
2017: PloS One
https://www.readbyqxmd.com/read/28742317/disposable-microfluidic-immunoarray-device-for-sensitive-breast-cancer-biomarker-detection
#2
Ricardo A G de Oliveira, Elsa María Materón, Matias Eliseo Melendez, Andre L Carvalho, Ronaldo C Faria
Breast cancer is the most common cancer in women worldwide. The detection of biomarkers has played a significant role in the early diagnosis and prognosis of breast cancer. Herein, we describe the construction of a disposable microfluidic immunoarray device (DµID) for rapid and low-cost detection of CA15-3 a protein biomarker for breast cancer. The DµID was constructed using a simple and rapid prototyping technique and was applied to detect CA15-3 in cancer patients. The DµID construction was based on a use of double-sided adhesive card with the microfluidic channel and a screen-printed array with 8 electrodes...
July 25, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28742147/genetic-analysis-of-the-regulation-of-the-voltage-gated-calcium-channel-homolog-cch1-by-the-%C3%AE-subunit-homolog-ecm7-and-cortical-er-protein-scs2-in-yeast
#3
Takafumi Kato, Aya Kubo, Tatsuya Nagayama, Shinichiro Kume, Chikara Tanaka, Yoshitaka Nakayama, Kazuko Iida, Hidetoshi Iida
The yeast Cch1/Mid1 Ca2+ channel is equivalent to animal voltage-gated Ca2+ channels and activated in cells incubated in low Ca2+ medium. We herein investigated the third subunit, Ecm7, under the same cell culture conditions. The deletion of ECM7 slightly lowered Ca2+ influx activity in the CNB1+ background, in which calcineurin potentially dephosphorylates Cch1, but markedly lowered this activity in the cnb1Δ background. The deletion of the C-terminal cytoplasmic region of Ecm7 also reduced Ca2+ influx activity...
2017: PloS One
https://www.readbyqxmd.com/read/28742025/structure-and-reconstitution-of-yeast-mpp6-nuclear-exosome-complexes-reveals-that-mpp6-stimulates-rna-decay-and-recruits-the-mtr4-helicase
#4
Elizabeth V Wasmuth, John C Zinder, Dimitrios Zattas, Mom Das, Christopher D Lima
Nuclear RNA exosomes catalyze a range of RNA processing and decay activities that are coordinated in part by cofactors, including Mpp6, Rrp47, and the Mtr4 RNA helicase. Mpp6 interacts with the nine-subunit exosome core, while Rrp47 stabilizes the exoribonuclease Rrp6 and recruits Mtr4, but it is less clear if these cofactors work together. Using biochemistry with Saccharomyces cerevisiae proteins, we show that Rrp47 and Mpp6 stimulate exosome-mediated RNA decay, albeit with unique dependencies on elements within the nuclear exosome...
July 25, 2017: ELife
https://www.readbyqxmd.com/read/28741179/activation-of-liver-x-receptor-inhibits-oct2-mediated-organic-cation-transport-in-renal-proximal-tubular-cells
#5
Teerasak Wongwan, Suticha Kittayaruksakul, Nithi Asavapanumas, Varanuj Chatsudthipong, Sunhapas Soodvilai
Liver X receptor (LXR) is transcriptional factor that plays an important role in the regulation of energy metabolism such as cholesterol, lipid, and glucose metabolism as well as membrane transporters and channels. Using both in vitro and in vivo models, LXR regulation of the expression and function of renal organic cation transporter 2 (OCT2) was observed. Synthetic LXR agonist (GW3965) and endogenous LXR agonist (22R-hydroxycholesterol) significantly reduced the uptake of (3)H-MPP(+), a prototypic substrate of OCT2, in both OCT2- Chinese hamster ovary K1 and human renal proximal tubular cells (RPTEC/TERT1)...
July 25, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28740863/a-nanosecond-time-resolved-xfel-analysis-of-structural-changes-associated-with-co-release-from-cytochrome-c-oxidase
#6
Atsuhiro Shimada, Minoru Kubo, Seiki Baba, Keitaro Yamashita, Kunio Hirata, Go Ueno, Takashi Nomura, Tetsunari Kimura, Kyoko Shinzawa-Itoh, Junpei Baba, Keita Hatano, Yuki Eto, Akari Miyamoto, Hironori Murakami, Takashi Kumasaka, Shigeki Owada, Kensuke Tono, Makina Yabashi, Yoshihiro Yamaguchi, Sachiko Yanagisawa, Miyuki Sakaguchi, Takashi Ogura, Ryo Komiya, Jiwang Yan, Eiki Yamashita, Masaki Yamamoto, Hideo Ago, Shinya Yoshikawa, Tomitake Tsukihara
Bovine cytochrome c oxidase (CcO), a 420-kDa membrane protein, pumps protons using electrostatic repulsion between protons transferred through a water channel and net positive charges created by oxidation of heme a (Fe a ) for reduction of O2 at heme a3 (Fe a3). For this process to function properly, timing is essential: The channel must be closed after collection of the protons to be pumped and before Fe a oxidation. If the channel were to remain open, spontaneous backflow of the collected protons would occur...
July 2017: Science Advances
https://www.readbyqxmd.com/read/28740490/inhibition-of-the-nod-like-receptor-protein-3-inflammasome-is-protective-in-juvenile-influenza-a-virus-infection
#7
Bria M Coates, Kelly L Staricha, Nandini Ravindran, Clarissa M Koch, Yuan Cheng, Jennifer M Davis, Dale K Shumaker, Karen M Ridge
Influenza A virus (IAV) is a significant cause of life-threatening lower respiratory tract infections in children. Antiviral therapy is the mainstay of treatment, but its effectiveness in this age group has been questioned. In addition, damage inflicted on the lungs by the immune response to the virus may be as important to the development of severe lung injury during IAV infection as the cytotoxic effects of the virus itself. A crucial step in the immune response to IAV is activation of the NOD-like receptor protein 3 (NLRP3) inflammasome and the subsequent secretion of the inflammatory cytokines, interleukin-1β (IL-1β), and interleukin-18 (IL-18)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28739446/crystallographic-insights-into-a-cobalt-iii-sepulchrate-based-alternative-cofactor-system-of-p450-bm3-monooxygenase
#8
Saravanan Panneerselvam, Aamir Shehzad, Jochen Mueller-Dieckmann, Matthias Wilmanns, Marco Bocola, Mehdi D Davari, Ulrich Schwaneberg
P450 BM3 is a multi-domain heme-containing soluble bacterial monooxygenase. P450 BM3 and variants are known to oxidize structurally diverse substrates. Crystal structures of individual domains of P450 BM3 are available. However, the spatial organization of the full-length protein is unknown. In this study, crystal structures of the P450 BM3 M7 heme domain variant with and without cobalt (III) sepulchrate are reported. Cobalt (III) sepulchrate acts as an electron shuttle in an alternative cofactor system employing zinc dust as the electron source...
July 21, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28739325/d242n-a-kv7-1-lqts-mutation-uncovers-a-key-residue-for-iks-voltage-dependence
#9
Cristina Moreno, Anna Oliveras, Chiara Bartolucci, Carmen Muñoz, Alicia de la Cruz, Diego A Peraza, Juan R Gimeno, Mercedes Martín-Martínez, Stefano Severi, Antonio Felipe, Pier D Lambiase, Teresa Gonzalez, Carmen Valenzuela
KV7.1 and KCNE1 co-assemble to give rise to the IKs current, one of the most important repolarizing currents of the cardiac action potential. Its relevance is underscored by the identification of >500 mutations in KV7.1 and, at least, 36 in KCNE1, that cause Long QT Syndrome (LQTS). The aim of this study was to characterize the biophysical and cellular consequences of the D242N KV7.1 mutation associated with the LQTS. The mutation is located in the S4 transmembrane segment, within the voltage sensor of the KV7...
July 21, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28736757/malaria-parasite-proteins-involved-in-nutrient-channels-at-the-host-erythrocyte-membrane-advances-and-questions-for-future-research
#10
S Chalapareddy, S A Desai
Erythrocytes infected malaria parasites have increased permeability to nutrients and other solutes, as mediated by an unusual ion channel known as the plasmodial surface anion channel (PSAC). Although the increased permeability of infected erythrocytes was identified more than 70 years ago and subsequently characterized with tracer studies, its mechanism and role in parasite biology remained unclear until the introduction of patch-clamp methods and high-throughput screening technologies. These methods discovered and implicated PSAC as the primary mechanism, determined that this channel is essential for parasite development, led to identification of the channel's genes, and stimulated antimalarial drug discovery against this target...
March 2017: Int J Curr Multidiscip Stud
https://www.readbyqxmd.com/read/28736364/-angiotensin-1-7-protects-cardiac-myocytes-against-high-glucose-induced-injury-by-inhibiting-clc-3-chloride-channels
#11
Shao-Ai Ccai, Jing-Fu Chen, Mei-Ji Chen, Jian-Cong Lin, Jian-Qiang Feng, Kai Lin, Xi-Mei Zhi, Wei-Jie Zhang, Wen Wu
OBJECTIVE: To explore whether angiotensin-(1-7) [Ang-(1-7)] protects cardiac myocytes against high glucose (HG)-induced injury by inhibiting ClC-3 chloride channels. METHOD: H9c2 cardiac cells were exposed to 35 mmol/L glucose for 24 h to establish a cell injury model. The cells were treated with Ang-(1-7) or the inhibitor of chloride channel (NPPB) in the presence of HG for 24 h to observe the changes in HG-induced cell injury. Cell counter kit 8 (CCK-8) assay was used to test the cell viability, and the morphological changes of the apoptotic cells were detected using Hoechst 33258 staining and fluorescent microscopy...
July 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28736242/suppression-of-cortical-trpm7-protein-attenuates-oxidative-damage-after-traumatic-brain-injury-via-akt-endothelial-nitric-oxide-synthase-pathway
#12
Hong-Liang Xu, Meng-Dong Liu, Xiao-Hong Yuan, Chun-Xi Liu
Neuronal death after traumatic brain injury (TBI) is a complex process resulting from a combination of factors, many of which are still unknown. Transient receptor potential melastatin 7 (TRPM7) is a transient receptor potential channel that has been demonstrated to mediate ischemic and traumatic neuronal injury in vitro. In the present study, TRPM7 was suppressed in the rat cerebral cortex by intracortical injections of viral vectors bearing shRNA specific for TRPM7 to investigate its potential role in an in vivo TBI model...
July 20, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28735901/mechanisms-of-pannexin1-channel-gating-and-regulation
#13
REVIEW
Paige Whyte-Fagundes, Georg Zoidl
Pannexins are a family of integral membrane proteins with distinct post-translational modifications, sub-cellular localization and tissue distribution. Panx1 is the most studied and best-characterized isoform of this gene family. The ubiquitous expression, as well as its function as a major ATP release and nucleotide permeation channel, makes Panx1 a primary candidate for participating in the pathophysiology of CNS disorders. While many investigations revolve around Panx1 functions in health and disease, more recently, details started emerging about mechanisms that control Panx1 channel activity...
July 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28735419/modulation-of-human-kv4-3-kchip2-channel-inactivation-kinetics-by-cytoplasmic-ca-2
#14
Christiane Groen, Robert Bähring
The transient outward current (I to) in the human heart is mediated by Kv4.3 channels complexed with Kv channel interacting protein (KChIP) 2, a cytoplasmic Ca(2+)-binding EF-hand protein known to modulate Kv4.3 inactivation gating upon heterologous co-expression. We studied Kv4.3 channels co-expressed with wild-type (wt) or EF-hand-mutated (ΔEF) KChIP2 in human embryonic kidney (HEK) 293 cells. Co-expression took place in the absence or presence of BAPTA-AM, and macroscopic currents were recorded in the whole-cell patch-clamp configuration with different free Ca(2+) concentrations in the patch-pipette...
July 22, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28734766/trpv1-modulates-morphine-induced-conditioned-place-preference-via-p38-mapk-in-the-nucleus-accumbens
#15
Sa-Ik Hong, Thi-Lien Nguyen, Shi-Xun Ma, Hyoung-Chun Kim, Seok-Yong Lee, Choon-Gon Jang
Emerging evidence suggests that the transient receptor potential vanilloid type 1 channel (TRPV1) is a novel target for the treatment of drug addiction, such as cocaine and morphine. Previously we reported that TRPV1 inhibition reduced morphine reward in the dorsal striatum (DSt) of mice and morphine self-administration through a decrease in accumbal activity in rats. However, the role of TRPV1 on morphine-conditioned reward in addiction-related brain regions, such as the nucleus accumbens (NAc), has not been previously established...
July 19, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28734106/insecticide-resistance-in-trialeurodes-vaporariorum-populations-and-novel-diagnostics-for-kdr-mutations
#16
Despoina Evr Kapantaidaki, Eldem Sadikoglou, Dimitra Tsakireli, Vasileios Kampanis, Marianna Stavrakaki, Corinna Schorn, Aris Ilias, Maria Riga, George Tsiamis, Ralf Nauen, George Skavdis, John Vontas, Anastasia Tsagkarakou
BACKGROUND: Neonicotinoids, pyrethroids and ketoenols, are currently used for the control of Trialeurodes vaporariorum (Hemiptera: Aleyrodidae). In this study, insecticide resistance status and mechanisms were investigated by classical bioassays and molecular techniques. RESULTS: Dose response bioassays were performed on 19 Greek populations, among the 35 different whitefly populations used for the whole analysis. Resistance factors scaled up to 207-, 4657- and 59- fold, for imidacloprid, bifenthrin and spiromesifen, respectively...
July 22, 2017: Pest Management Science
https://www.readbyqxmd.com/read/28734079/post-translational-palmitoylation-controls-the-voltage-gating-and-lipid-raft-association-of-calhm1-channel
#17
Akiyuki Taruno, Hongxin Sun, Koichi Nakajo, Tatsuro Murakami, Yasuyoshi Ohsaki, Mizuho A Kido, Fumihito Ono, Yoshinori Marunaka
Emerging roles of CALHM1, a recently discovered voltage-gated ion channel, include purinergic neurotransmission of tastes in taste buds and memory formation in the brain, highlighting its physiological importance. However, the regulatory mechanisms of the CALHM1 channel remain entirely unexplored, hindering full understanding of its contribution in vivo. In fact, the different gating properties of CALHM1 in vivo and in vitro suggest undiscovered regulatory mechanisms. Here, in searching for post-translational regulatory mechanisms, we discovered the regulation of CALHM1 gating and association with lipid microdomains via protein S-palmitoylation, the only reversible lipid modification of proteins on cysteine residues...
July 22, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28733955/detection-of-plasma-biomarkers-using-immunomagnetic-reduction-a-promising-method-for-the-early-diagnosis-of-alzheimer-s-disease
#18
REVIEW
Shieh-Yueh Yang, Ming-Jang Chiu, Ta-Fu Chen, Herng-Er Horng
Alzheimer's disease (AD) is the most common form of dementia. The development of assay technologies able to diagnose early-stage AD is important. Blood tests to detect biomarkers, such as amyloid and total Tau protein, are among the most promising diagnostic methods due to their low cost, low risk, and ease of operation. However, such biomarkers in blood occur at extremely low levels and are difficult to detect precisely. In the early 2000s, a highly sensitive assay technology, immunomagnetic reduction (IMR), was developed...
July 2017: Neurology and Therapy
https://www.readbyqxmd.com/read/28733581/structural-determinants-at-the-m2-muscarinic-receptor-modulate-the-rgs4-girk-response-to-pilocarpine-by-impairment-of-the-receptor-voltage-sensitivity
#19
I-Shan Chen, Kazuharu Furutani, Yoshihisa Kurachi
Membrane potential controls the response of the M2 muscarinic receptor to its ligands. Membrane hyperpolarization increases response to the full agonist acetylcholine (ACh) while decreasing response to the partial agonist pilocarpine. We previously have demonstrated that the regulator of G-protein signaling (RGS) 4 protein discriminates between the voltage-dependent responses of ACh and pilocarpine; however, the underlying mechanism remains unclear. Here we show that RGS4 is involved in the voltage-dependent behavior of the M2 muscarinic receptor-mediated signaling in response to pilocarpine...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28733455/e3-ubiquitin-ligase-nedd4-induces-endocytosis-and-lysosomal-sorting-of-connexin43-to-promote-loss-of-gap-junctions
#20
Max Z Totland, Christian H Bergsland, Tone A Fykerud, Lars M Knudsen, Nikoline L Rasmussen, Peter W Eide, Zeremariam Yohannes, Vigdis Sørensen, Andreas Brech, Ragnhild A Lothe, Edward Leithe
Intercellular communication via gap junctions has an important role in controlling cell growth and in maintaining tissue homeostasis. Connexin43 is the most abundantly expressed gap junction channel protein in humans and acts as a tumor suppressor in multiple tissue types. Connexin43 is often dysregulated at the post-translational level during cancer development, resulting in loss of gap junctions. However, the molecular basis underlying the aberrant regulation of connexin43 in cancer cells has remained elusive...
July 21, 2017: Journal of Cell Science
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