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https://www.readbyqxmd.com/read/27924833/tgf%C3%AE-2-induced-outflow-alterations-in-a-bioengineered-trabecular-meshwork-are-offset-by-a-rho-associated-kinase-inhibitor
#1
Karen Y Torrejon, Ellen L Papke, Justin R Halman, Magnus Bergkvist, John Danias, Susan T Sharfstein, Yubing Xie
Members of the transforming growth factor beta (TGFβ) cytokine family have long been associated with affecting several cellular functions, including cell proliferation, differentiation and extracellular matrix (ECM) turnover. Of particular interest to this work, TGFβ2 has been linked to most types of glaucomas as a potential fibrotic agent that can cause elevation of intraocular pressure (IOP). Given that the trabecular meshwork (TM) provides most of aqueous humor outflow resistance in the eye, an in vitro bioengineered human TM (HTM) model has been created and validated by analyzing effects of TGFβ2 on transcellular pressure changes and outflow facility...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27919951/rho-associated-protein-kinase-rock-inhibitors-inhibit-survivin-expression-and-sensitize-pancreatic-cancer-stem-cells-to-gemcitabine
#2
Hiroyuki Takeda, Masashi Okada, Shuhei Suzuki, Kenta Kuramoto, Hirotsugu Sakaki, Hikaru Watarai, Tomomi Sanomachi, Shizuka Seino, Takashi Yoshioka, Chifumi Kitanaka
BACKGROUND: Targeting pathways regulating survivin expression, which has been implicated in multidrug resistance of cancer cells, is a promising strategy to overcome cancer chemoresistance. To date, the role of rho-associated protein kinases (ROCKs) in survivin expression remains largely unknown. MATERIALS AND METHODS: The effects of ROCK inhibitors Y-27632 and fasudil on survivin expression and cell viability were determined by immunoblot analysis and dye exclusion, respectively, in PANC-1 CSLC, a cancer stem cell line derived from a serum-cultured, gemcitabine-sensitive pancreatic cancer cell line, PANC-1...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27917718/the-role-of-rho-kinase-inhibitors-in-corneal-endothelial-dysfunction
#3
Naoki Okumura, Shigeru Kinoshita, Noriko Koizumi
BACKGROUND: The cornea is transparent tissue that serves as the window of the eye, allowing light to enter from the outer environment. The corneal endothelium maintains corneal transparency; thus, its dysfunction results in corneal haziness and causes severe vision loss. The only available therapeutic choice for treating corneal endothelial dysfunction has been transplantation using donor corneas; consequently, researchers have been pressed to develop new therapeutic options. METHODS: The goal of the review is to provide an overview of the research into Rho kinase (ROCK) inhibitors in the field of corneal endothelium therapy and the potential for clinical use of ROCK inhibitors...
December 5, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27917007/roles-of-ras-homolog-a-in-invasive-ductal-breast-carcinoma
#4
Eriko Murakami, Yoko Nakanishi, Yukari Hirotani, Sumie Ohni, Xiaoyan Tang, Shinobu Masuda, Katsuhisa Enomoto, Kenichi Sakurai, Sadao Amano, Tsutomu Yamada, Norimichi Nemoto
Breast cancer has a poor prognosis owing to tumor cell invasion and metastasis. Although Ras homolog (Rho) A is involved in tumor cell invasion, its role in breast carcinoma is unclear. Here, RhoA expression was examined in invasive ductal carcinoma (IDC), with a focus on its relationships with epidermal-mesenchymal transition (EMT) and collective cell invasion. Forty-four surgical IDC tissue samples and two normal breast tissue samples were obtained. RhoA, E-cadherin, vimentin, and F-actin protein expression were analyzed by immunohistochemistry...
November 1, 2016: Acta Histochemica et Cytochemica
https://www.readbyqxmd.com/read/27914611/restoration-of-uridine-5-triphosphate-suppressed-delayed-rectifying-k-currents-by-an-no-activator-kmup-1-involves-rhoa-rho-kinase-signaling-in-pulmonary-artery-smooth-muscle-cells
#5
Zen-Kong Dai, Chang-Ling Kao, Su-Ling Hsieh, Ing-Jun Chen, Bin-Nan Wu
We have demonstrated that KMUP-1 (7-[2-[4-(2-chlorobenzene)piperazinyl]ethyl]-1,3-dimethylxanthine) blunts monocrotaline-induced pulmonary arterial hypertension by altering Ca(2+) sensitivity, K(+)-channel function, endothelial nitric oxide synthase activity, and RhoA/Rho kinase (ROCK) expression. This study further investigated whether KMUP-1 impedes uridine 5'-triphosphate (UTP)-inhibited delayed rectifying K(+) (KDR) current in rat pulmonary arteries involved the RhoA/ROCK signaling. Pulmonary artery smooth muscle cells (PASMCs) were enzymatically dissociated from rat pulmonary arteries...
December 2016: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/27914563/differential-effects-of-testosterone-and-estradiol-on-clitoral-function-an-experimental-study-in-rats
#6
Paolo Comeglio, Ilaria Cellai, Sandra Filippi, Chiara Corno, Francesca Corcetto, Annamaria Morelli, Elena Maneschi, Elisa Maseroli, Edoardo Mannucci, Massimiliano Fambrini, Mario Maggi, Linda Vignozzi
INTRODUCTION: Female sexual response is a complex phenomenon in which psychological, neurologic, and vascular mechanisms and hormonal factors interact. During the arousal phase, they cooperate to increase genital blood flow, thus inducing engorgement of the clitoris and lubrication of the vagina. Regulation of vascular and non-vascular smooth muscle tone is the crucial event in the erectile process. Preclinical studies have suggested that nitric oxide (NO) is the main vasodilator neurotransmitter modulating, through the second messenger cyclic guanosine monophosphate (cGMP), clitoral flow vessels...
December 2016: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/27904131/mir-31-regulates-rho-associated-kinase-myosin-light-chain-rock-mlc-pathway-and-inhibits-gastric-cancer-invasion-roles-of-rhoa
#7
Zhuo Chen, Shengnan Liu, Yuan Xia, Kejian Wu
BACKGROUND This study evaluated how the expression of miR-31 can be used to detect gastric cancer (GC) to help illuminate the role of miR-31 and RhoA in GC cells. MATERIAL AND METHODS We carried out our experiments using tissue specimens from 70 GC patients. The relative expression of miR-31 and RhoA mRNA in tissues and cells was detected by RT-PCR. The expression level of RhoA protein was detected by immunohistochemistry. GC cell line BGC-823 was transfected with six groups of vectors: blank group, NC (negative control) group, miR-31 mimics group, miR-31 mimics + RhoA group, miR-31 mimics + ROCK group, and miR-31 mimics + MLCK agonist group...
December 1, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27899893/raynaud-s-phenomenon-a-brief-review-of-the-underlying-mechanisms
#8
REVIEW
Manal M Fardoun, Joseph Nassif, Khodr Issa, Elias Baydoun, Ali H Eid
Raynaud's phenomenon (RP) is characterized by exaggerated cold-induced vasoconstriction. This augmented vasoconstriction occurs by virtue of a reflex response to cooling via the sympathetic nervous system as well as by local activation of α2C adrenoceptors (α2C-AR). In a cold-initiated, mitochondrion-mediated mechanism involving reactive oxygen species and the Rho/ROCK pathway, cytoskeletal rearrangement in vascular smooth muscle cells orchestrates the translocation of α2C-AR to the cell membrane, where this receptor readily interacts with its ligand...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27886408/role-of-rock2-in-cd4-cells-in-allergic-airways-responses-in-mice
#9
David I Kasahara, Joel A Mathews, Fernanda M C Ninin, Allison P Wurmbrand, James K Liao, Stephanie A Shore
BACKGROUND: Rho kinases (ROCKs) contribute to allergic airways disease. ROCKs also play a role in lymphocyte proliferation and migration. OBJECTIVE: To determine the role of ROCK2 acting within CD4(+) cells in allergic airways responses. METHODS: ROCK2 haploinsufficient (ROCK2(+/-) ) and wildtype mice were sensitized with ovalbumin (OVA). ROCK2(+/-) mice then received either CD4(+) cells from ROCK2 sufficient OVA TCR transgenic (OT-II) mice or saline i...
November 25, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27883058/role-of-ectonucleotide-pyrophosphatase-phosphodiesterase-2-in-the-midline-axis-formation-of-zebrafish
#10
Frisca Frisca, Daniel Colquhoun, Yona Goldshmit, Minna-Liisa Änkö, Alice Pébay, Jan Kaslin
Lysophosphatidic acid (LPA) is a unique bioactive lysophospholipid that induces pleiotropic effects in various cell types and organisms by acting on its specific receptors. LPA is mainly synthetised extracellularly by the ectonucleotide pyrophosphatase/phosphodiesterase 2/autotaxin (enpp2). Altered LPA signalling is associated with embryonic abnormalities, suggesting critical roles for LPA during development. However, the role of LPA signalling during early embryogenesis is not well established. We demonstrate that enpp2/LPA signalling in the early zebrafish embryo results in altered axis and midline formation, defects in left right (L-R) patterning, ciliogenesis of the Kupffer's vesicle (KV), through the modulation of cell migration during gastrulation in a lpar1-3 Rho/ROCK-dependant manner...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27880913/mdia-and-rock-mediate-actin-dependent-presynaptic-remodeling-regulating-synaptic-efficacy-and-anxiety
#11
Yuichi Deguchi, Masaya Harada, Ryota Shinohara, Michael Lazarus, Yoan Cherasse, Yoshihiro Urade, Daisuke Yamada, Masayuki Sekiguchi, Dai Watanabe, Tomoyuki Furuyashiki, Shuh Narumiya
Here, we show neuronal inactivation-induced presynaptic remodeling and involvement of the mammalian homolog of Diaphanous (mDia) and Rho-associated coiled-coil-containing kinase (ROCK), Rho-regulated modulators of actin and myosin, in this process. We find that social isolation induces inactivation of nucleus accumbens (NAc) neurons associated with elevated anxiety-like behavior, and that mDia in NAc neurons is essential in this process. Upon inactivation of cultured neurons, mDia induces circumferential actin filaments around the edge of the synaptic cleft, which contract the presynaptic terminals in a ROCK-dependent manner...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27856608/reversal-of-bone-marrow-mobilopathy-and-enhanced-vascular-repair-by-angiotensin-1-7-in-diabetes
#12
Goutham Vasam, Shrinidh Joshi, Sean E Thatcher, Stephen H Bartelmez, Lisa A Cassis, Yagna Pr Jarajapu
Ang-(1-7)/MasR pathway activates vascular repair-relevant functions of bone marrow progenitor cells. We tested the effects of Ang-(1-7) on mobilization and vasoreparative functions of progenitor cells that are impaired in diabetes. Study was carried out in streptozotocin-induced diabetic or db/db mice. Diabetes resulted in decreased number of Lineage(-) Sca-1(+) c-Kit(+) (LSK) cells in the circulation, which was normalized by Ang-(1-7). Diabetes-induced depletion of LSK cells in the bone marrow was reversed by Ang-(1-7)...
November 17, 2016: Diabetes
https://www.readbyqxmd.com/read/27852748/quantitative-gtpase-affinity-purification-identifies-rho-family-protein-interaction-partners
#13
Florian E Paul, Henrik Zauber, Laura von Berg, Oliver Rocks, Oliver Daumke, Matthias Selbach
Although Rho GTPases are essential molecular switches involved in many cellular processes, an unbiased experimental comparison of their interaction partners was not yet performed. Here, we develop quantitative GTPase affinity purification (qGAP) to systematically identify interaction partners of six Rho GTPases (Cdc42, Rac1, RhoA, RhoB, RhoC, RhoD) depending on their nucleotide loading state. The method works with cell line or tissue-derived protein lysates in combination with SILAC-based or label free quantification, respectively...
November 16, 2016: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/27849131/spatial-rho-regulation-molecular-mechanisms-controlling-the-gap-protein-dlc3
#14
Janina Hendrick, Monilola A Olayioye
The spatial regulation of cellular Rho signaling by GEF and GAP proteins and the molecular mechanisms controlling the Rho regulators themselves are still incompletely understood. We previously reported that the poorly characterized RhoGAP protein DLC3 localizes to cell-cell adhesions and Rab8-positive membrane tubules. However, it was unclear how DLC3 is targeted to these subcellular sites to execute its functions. In our recent work, protein partners of DLC3 were identified by mass spectrometry, identifying the basolateral polarity protein Scribble as a scaffold for DLC3 at cell-cell contacts...
November 16, 2016: Small GTPases
https://www.readbyqxmd.com/read/27847705/a-model-of-glial-scarring-analogous-to-the-environment-of-a-traumatically-injured-spinal-cord-using-kainate
#15
Jong Yoon Yoo, Chang Ho Hwang, Hea Nam Hong
OBJECTIVE: To develop an in vitro model analogous to the environment of traumatic spinal cord injury (SCI), the authors evaluated change of astrogliosis following treatments with kainate and/or scratch, and degree of neurite outgrowth after treatment with a kainate inhibitor. METHODS: Astrocytes were obtained from the rat spinal cord. Then, 99% of the cells were confirmed to be GFAP-positive astrocytes. For chemical injury, the cells were treated with kainate at different concentrations (10, 50 or 100 µM)...
October 2016: Annals of Rehabilitation Medicine
https://www.readbyqxmd.com/read/27846787/cryopreservation-of-brain-endothelial-cells-derived-from-human-induced-pluripotent-stem-cells-is-enhanced-by-rock-inhibition
#16
Hannah Kathryn Wilson, Madeline G Faubion, Michael K Hjortness, Sean P Palecek, Eric V Shusta
The blood-brain barrier (BBB) maintains brain homeostasis but also presents a major obstacle to brain drug delivery. Brain microvascular endothelial cells (BMECs) form the principal barrier and therefore represent the major cellular component of in vitro BBB models. Such models are often used for mechanistic studies of the BBB in health and disease and for drug screening. Recently, human induced pluripotent stem cells (iPSCs) have emerged as a new source for generating BMEC-like cells for use in in vitro human BBB studies...
November 15, 2016: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/27836552/rhoa-rock-pathway-activity-is-essential-for-the-correct-localization-of-the-germ-plasm-mrnas-in-zebrafish-embryos
#17
Jerónimo Roberto Miranda-Rodríguez, Enrique Salas-Vidal, Hilda Lomelí, Mario Zurita, Denhi Schnabel
Zebrafish germ plasm is composed of mRNAs such as vasa and nanos and of proteins such as Bucky ball, all of which localize symmetrically in four aggregates at the distal region of the first two cleavage furrows. The coordination of actin microfilaments, microtubules and kinesin is essential for the correct localization of the germ plasm. Rho-GTPases, through their effectors, coordinate cytoskeletal dynamics. We address the participation of RhoA and its effector ROCK in germ plasm localization during the transition from two- to eight-cell embryos...
November 9, 2016: Developmental Biology
https://www.readbyqxmd.com/read/27830834/suilysin-induced-platelet-neutrophil-complexes-formation-is-triggered-by-pore-formation-dependent-calcium-influx
#18
Shengwei Zhang, Yuling Zheng, Shaolong Chen, Shujing Huang, Keke Liu, Qingyu Lv, Yongqiang Jiang, Yuan Yuan
Platelet activation and platelet-neutrophil interactions have been found to be involved in inflammation, organ failure and soft-tissue necrosis in bacterial infections. Streptococcus suis, an emerging human pathogen, can cause streptococcal toxic-shock syndrome (STSS) similarly to Streptococcus pyogenes. Currently, S. suis-platelet interactions are poorly understood. Here, we found that suilysin (SLY), the S. suis cholesterol-dependent cytolysin (CDC), was the sole stimulus of S. suis that induced platelet-neutrophil complexes (PNC) formation...
November 10, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27825172/oxidized-low-density-lipoprotein-induced-cyclophilin-a-secretion-requires-rock-dependent-diphosphorylation-of-myosin-light-chain
#19
Zizhuo Su, Rongjie Lin, Yuyang Chen, Xiaorong Shu, Haifeng Zhang, Shumin Liang, Ruqiong Nie, Jingfeng Wang, Shuanglun Xie
OBJECTIVE: Accumulation of cyclophilin A (CyPA) within atherosclerotic lesions is thought to be implicated in the progression of atherosclerosis. However, the source of CyPA within atherosclerotic lesions is still unknown. The aim of this study is to determine the role of oxidized low-density lipoproteins (ox-LDL) in vascular smooth muscle cell (VSMC)-derived CyPA secretion and the underlying mechanism. METHODS AND RESULTS: Abundant CyPA and α-smooth muscle actin (α-SMA) expressed in atherosclerotic lesions was observed in apolipoprotein E-deficient mice...
November 9, 2016: Journal of Vascular Research
https://www.readbyqxmd.com/read/27824338/rock-signalling-induced-gene-expression-changes-in-mouse-pancreatic-ductal-adenocarcinoma-cells
#20
Nicola Rath, Gabriela Kalna, William Clark, Michael F Olson
The RhoA and RhoC GTPases act via the ROCK1 and ROCK2 kinases to promote actomyosin contraction, resulting in directly induced changes in cytoskeleton structures and altered gene transcription via several possible indirect routes. Elevated activation of the Rho/ROCK pathway has been reported in several diseases and pathological conditions, including disorders of the central nervous system, cardiovascular dysfunctions and cancer. To determine how increased ROCK signalling affected gene expression in pancreatic ductal adenocarcinoma (PDAC) cells, we transduced mouse PDAC cell lines with retroviral constructs encoding fusion proteins that enable conditional activation of ROCK1 or ROCK2, and subsequently performed RNA sequencing (RNA-Seq) using the Illumina NextSeq 500 platform...
November 8, 2016: Scientific Data
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