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https://www.readbyqxmd.com/read/28526517/regulation-of-rhoa-rock-and-sustained-arterial-contraction-by-low-cytosolic-ca-2-levels-during-prolonged-depolarization-of-arterial-smooth-muscle
#1
Cristina Porras-González, Antonio Ordóñez, Antonio Castellano, Juan Ureña
The role of L-type Ca(2+) channels (LTCCs) and RhoA/Rho kinase (ROCK) on depolarization-induced sustained arterial contraction lasting several minutes is already known. However, in vivo, vascular smooth muscle cells can be depolarized for longer periods, inducing substantial inactivation of LTCCs and markedly reducing Ca(2+) influx into the myocytes. We have examined, in femoral arterial rings, the role of LTCCs and RhoA/ROCK during long-lasting depolarization. Our results reveal a new vasoreactive response after 20-30min of depolarization in 2...
May 16, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28521412/microrna-335-and-its-target-rock1-synergistically-influence-tumor-progression-and-prognosis-in-osteosarcoma
#2
Yong Wang, Ningning Wang, Xiandong Zeng, Jie Sun, Guangbin Wang, Huimian Xu, Wei Zhao
MicroRNA (miR)-335 and Rho-associated serine-threonine protein kinase 1 (Rock1) is ectopically expressed in multiple malignant tumors including osteosarcoma. The present study aimed to clarify whether the combined ectopically expressed miR-335 and Rock1 was correlated with clinicopathological features and prognosis in patients with osteosarcoma. The expression of miR-335 and Rock1 in 91 osteosarcoma tissue samples and 47 noncancerous bone tissues were determined respectively by in situ hybridization and immunohistochemistry...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521307/downregulation-of-x-linked-inhibitor-of-apoptosis-protein-by-7-benzylidenenaltrexone-maleate-sensitizes-pancreatic-cancer-cells-to-trail-induced-apoptosis
#3
So Young Kim, Sojung Park, SeonA Yoo, Jin Kyung Rho, Eun Sung Jun, Suhwan Chang, Kyung Kon Kim, Song Cheol Kim, Inki Kim
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential biological anticancer agent. However, a wide range of human primary cancers, including pancreatic cancer, display resistance to apoptosis induction by TRAIL. Therefore, this resistance needs to be overcome to allow TRAIL to be successfully used in cancer therapy. In this study, we performed a compound screen to isolate TRAIL sensitizers and found that one of the identified compounds, 7-benzylidenenaltrexone maleate (BNTX), sensitized pancreatic cancer cells to TRAIL-induced apoptotic cell death...
May 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28515690/brain-renin-angiotensin-system-and-microglial-polarization-implications-for-aging-and-neurodegeneration
#4
REVIEW
Jose L Labandeira-Garcia, Ana I Rodríguez-Perez, Pablo Garrido-Gil, Jannette Rodriguez-Pallares, Jose L Lanciego, Maria J Guerra
Microglia can transform into proinflammatory/classically activated (M1) or anti-inflammatory/alternatively activated (M2) phenotypes following environmental signals related to physiological conditions or brain lesions. An adequate transition from the M1 (proinflammatory) to M2 (immunoregulatory) phenotype is necessary to counteract brain damage. Several factors involved in microglial polarization have already been identified. However, the effects of the brain renin-angiotensin system (RAS) on microglial polarization are less known...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28513223/activation-of-thromboxane-a2-receptors-mediates-endothelial-dysfunction-in-diabetic-mice
#5
Xiaona Xie, Wanchun Sun, Jun Wang, Xiaoou Li, Xiaofeng Liu, Ning Liu
BACKGROUND: Diabetes is one of high-risk factors for cardiovascular disease. Improvement of endothelial dysfunction in diabetes reduces vascular complications. However, the underlying mechanism needs to be uncovered. This study was conducted to elucidate whether and how thromboxane A2 receptor (TPr) activation contributes to endothelial dysfunction in diabetes. METHODS AND RESULTS: Exposure of human umbilical vein endothelial cells (HUVECs) to either TPr agonists, two structurally related thromboxane A2 (TxA2) mimetics, significantly reduced phosphorylations of endothelial nitric oxide synthase (eNOS) at Ser(1177) and Akt at Ser(473)...
May 17, 2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/28510599/selective-inhibition-of-brain-endothelial-rho-kinase-2-provides-optimal-protection-of-an-in-vitro-blood-brain-barrier-from-tissue-type-plasminogen-activator-and-plasmin
#6
Be'eri Niego, Natasha Lee, Pia Larsson, T Michael De Silva, Amanda E-Ling Au, Fiona McCutcheon, Robert L Medcalf
Rho-kinase (ROCK) inhibition, broadly utilised in cardiovascular disease, may protect the blood-brain barrier (BBB) during thrombolysis from rt-PA-induced damage. While the use of nonselective ROCK inhibitors like fasudil together with rt-PA may be hindered by possible hypotensive side-effects and inadequate capacity to block detrimental rt-PA activity in brain endothelial cells (BECs), selective ROCK-2 inhibition may overcome these limitations. Here, we examined ROCK-2 expression in major brain cells and compared the ability of fasudil and KD025, a selective ROCK-2 inhibitor, to attenuate rt-PA-induced BBB impairment in an in vitro human model...
2017: PloS One
https://www.readbyqxmd.com/read/28509381/topography-guided-control-of-local-migratory-behaviors-and-protein-expression-of-cancer-cells
#7
Jung-Youn Shin, Hong Nam Kim, Suk Ho Bhang, Jeong-Kee Yoon, Kahp-Yang Suh, Noo Li Jeon, Byung-Soo Kim
In vivo cancer cell migration and invasion are directed by biophysical guidance mechanisms such as pre-existing microtracks and basement membrane extracellular matrices. Here, this paper reports the correlation of the local migratory behavior of cancer cells and the biochemical signal expression using the topography that can guide or inhibit cell behaviors. To this end, the local apparent migration and the protein expression level are investigated with respect to the topographical feature size (flat, nanoline, and microline) and orientation (microline, microconcentric, and microradial) with the collectively migrating (A431) and individually migrating (MDA-MB-231 and U-87-MG) cancer cells...
May 16, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28509344/cgmp-signalling-inhibits-platelet-shape-change-through-regulation-of-the-rhoa-rho-kinase-mlc-phosphatase-signalling-pathway
#8
Ahmed Aburima, Kochar Walladbegi, Jonathan D Wake, Khalid M Naseem
BACKGROUND: Platelet shape change, spreading and thrombus stability requires activation of the actin cytoskeleton contractile machinery. The mechanisms controlling actin assembly to prevent unwanted platelet activation are unclear. OBJECTIVES: We examined the effects of nitric oxide on the signalling pathways regulating platelet actin-myosin activation. RESULTS: S-nitrosoglutathione (GSNO) inhibited thrombin-induced platelet shape change and myosin phosphorylation of myosin light chain (MLC)...
May 16, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28507312/design-and-evaluation-of-ephrina1-mutants-with-cerebral-protective-effect
#9
Yuanjun Zhu, Yuanqing Gao, Danping Zheng, Mengyang Shui, Kuai Yu, Xiaoyan Liu, Yuan Lin, Li Su, Wenxing Yang, Yinye Wang
The activation of EphA2 receptor by its natural ligand EphrinA1 causes blood brain barrier dysfunction, and inactivation of EphA2 reduces BBB damage in ischemic stroke. Thus, EphA2 targeted antagonists may serve as neuroprotective agents. We engineered four mutants of EphrinA1, EM1, EM2, EM3 and EM4, respectively. The computational analysis showed that these four mutants were capable of interacting with EphA2. Their potential neuroprotective effects were examined in mouse focal ischemia/reperfusion (I/R) model...
May 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28505515/rhob-induces-the-production-of-proinflammatory-cytokines-in-tlr-triggered-macrophages
#10
Shuyuan Liu, Lisong Huang, Zhusen Lin, Yuanqin Hu, Ruifeng Chen, Liqiu Wang, Yi Shan
Toll-like receptors (TLRs) are the primary sensors detecting conserved molecular patterns on microorganisms, thus acting as important components of innate immunity against invading pathogens. Many positive and negative regulators of TLR-triggered signaling have been identified. The Rho GTPase RhoB plays a key role in cell migration, division and polarity; however, the function and regulatory mechanisms of RhoB in TLR ligand-triggered innate immune responses remain to be investigated. Here, we report that the expression of RhoB is induced by TLR agonists (lipopolysaccharide (LPS), CpG, poly(I:C)) in macrophages...
May 12, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28501682/the-role-of-arachidonic-acid-cyclooxygenase-cascade-phosphodiesterase-iv-and-rho-kinase-in-h2s-induced-relaxation-in-the-mouse-corpus-cavernosum
#11
Fatma Aydinoglu, Nuran Ogulener
BACKGROUND: Penile corpus cavernosum is an extremely vascularized tissue and cavernosal smooth muscle tone is regulated by the balance between contractile and relaxant factor. We investigated the possible role of arachidonic acid/cyclooxygenase cascade, phosphodiesterase IV (PDEIV) and Rho-kinase in exogenous hydrogen sulfide (H2S)-induced relaxation in mouse corpus cavernosum. METHODS: The relaxant response to H2S (NaHS as exogenous H2S; 1-1000μM) were obtained in isolated mouse corpus cavernosum tissues which pre-contracted by phenylephrine (5μM)...
February 24, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28500348/penicillinase-resistant-antibiotics-induce-non-immune-mediated-cholestasis-through-hsp27-activation-associated-with-pkc-p38-and-pi3k-akt-signaling-pathways
#12
Audrey Burban, Ahmad Sharanek, Romain Hüe, Marion Gay, Sylvain Routier, André Guillouzo, Christiane Guguen-Guillouzo
The penicillinase-resistant antibiotics (PRAs), especially the highly prescribed flucloxacillin, caused frequent liver injury via mechanisms that remain largely non-elucidated. We first showed that flucloxacillin, independently of cytotoxicity, could exhibit cholestatic effects in human hepatocytes in the absence of an immune reaction, that were typified by dilatation of bile canaliculi associated with impairment of the Rho-kinase signaling pathway and reduced bile acid efflux. Then, we analyzed the sequential molecular events involved in flucloxacillin-induced cholestasis...
May 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28493050/fasudil-ameliorates-endothelial-dysfunction-in-streptozotocin-induced-diabetic-rats-a-possible-role-of-rho-kinase
#13
Amal Hofni, Basim A Shehata Messiha, Safwat A Mangoura
Endothelial dysfunction is a major contributor to the pathogenesis of vascular disease in diabetes mellitus and RhoA/Rho-kinase (ROCK) system appears to play a crucial role in this setting. The present study was conducted to investigate the effect of the selective ROCK inhibitor, fasudil, on diabetes-related endothelial dysfunction and elucidated its underlying mechanism(s). Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg), and fasudil (5 mg/kg per day) was orally administered for 8 weeks...
May 11, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28488809/optimized-isolation-and-expansion-of-human-airway-epithelial-basal-cells-from-endobronchial-biopsy-samples
#14
Kate H C Gowers, Robert E Hynds, Ricky M Thakrar, Bernadette Carroll, Martin A Birchall, Sam M Janes
Autologous airway epithelial cells have been used in clinical tissue-engineered airway transplantation procedures with a view to assisting mucosal regeneration and restoring mucociliary escalator function. However, limited time is available for epithelial cell expansion due to the urgent nature of these interventions and slow epithelial regeneration has been observed in patients. Human airway epithelial cells can be expanded from small biopsies or brushings taken during bronchoscopy procedures but the optimal mode of tissue acquisition from patients has not been investigated...
May 10, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28487954/rhoa-inhibits-apoptosis-and-increases-proliferation-of-cultured-spca1-lung-cancer-cells
#15
Dabei Liu, Xingke Mei, Linlin Wang, Xueying Yang
The Rho kinase pathway has previously been reported to possess a close relationship with the growth, migration and invasion of lung cancer cells. However, the molecular mechanisms underlying the effects of this pathway on lung cancer cells are still elusive. The aim of the present study was to investigate the effects and underlying molecular mechanisms of Ras homolog family member A (RhoA) on the proliferation and apoptosis of SPCA1 lung carcinoma cells. Stable SPCA1 lung cancer cell lines, in which RhoA expression was silenced by small interfering RNA, were isolated following Geneticin screening...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28487419/membrane-depolarization-activates-bk-channels-through-rock-mediated-%C3%AE-1-subunit-surface-trafficking-to-limit-vasoconstriction
#16
M Dennis Leo, Xue Zhai, Padmapriya Muralidharan, Korah P Kuruvilla, Simon Bulley, Frederick A Boop, Jonathan H Jaggar
Membrane depolarization of smooth muscle cells (myocytes) in the small arteries that regulate regional organ blood flow leads to vasoconstriction. Membrane depolarization also activates large-conductance calcium (Ca(2+))-activated potassium (BK) channels, which limits Ca(2+) channel activity that promotes vasoconstriction, thus leading to vasodilation. We showed that in human and rat arterial myocytes, membrane depolarization rapidly increased the cell surface abundance of auxiliary BK β1 subunits but not that of the pore-forming BKα channels...
May 9, 2017: Science Signaling
https://www.readbyqxmd.com/read/28487281/filamin-a-is-required-for-spindle-migration-and-asymmetric-division-in-mouse-oocytes
#17
HaiYang Wang, Jing Guo, ZiLi Lin, Suk Namgoong, Jeong Su Oh, Nam-Hyung Kim
Dynamic changes in the actin network are crucial for the cortical migration of spindles and establishment of polarity, to ensure asymmetric division during meiotic maturation. In this study, filamin A (FLNA) was found to be an essential actin regulator that controlled spindle migration and asymmetric division during oocyte meiosis. FLNA was localized in the cytoplasm and enriched at the cortex and near the chromosomes. Knockdown of FLNA impaired meiotic asymmetric division and spindle migration with a decrease in the amount of cytoplasmic actin mesh and cortical actin levels...
May 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28484504/effect-of-qskl-on-mapk-and-rhoa-pathways-in-a-rat-model-of-heart-failure
#18
Kai Xia, Qiyan Wang, Chun Li, Zifan Zeng, Yong Wang, Wei Wang
Qishenkeli (QSKL) is one of the Chinese medicine formulae for treating heart failure and has been shown to have an antifibrotic effect. However, the mechanism of its therapeutic effects remains unclear. In this study, we aimed to explore whether QSKL could exert an antifibrotic effect by attenuating ras homolog family member A (RhoA) and mitogen activated protein kinase (MAPK) pathways. Rats were randomly divided into sham group, model group, QSKL group, and positive control group. Heart failure was induced by ligation of the left ventricle anterior descending artery...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28484287/mir-135b-plays-a-neuroprotective-role-by-targeting-gsk3%C3%AE-in-mpp-intoxicated-sh-sy5y-cells
#19
Jianlei Zhang, Wei Liu, Yabo Wang, Shengnan Zhao, Na Chang
miR-135a-5p was reported to play a crucial role in the protective effects of hydrogen sulfide against Parkinson's disease (PD) by targeting rho-associated protein kinase 2 (ROCK2). However, the role of another member of miR-135 family (miR-135b) and the underlying mechanism in PD are still unclear. qRT-PCR and western blot showed that miR-135 was downregulated and glycogen synthase kinase 3β (GSK3β) was upregulated at mRNA and protein levels in MPP(+)-intoxicated SH-SY5Y cells in a dose- and time-dependent manner...
2017: Disease Markers
https://www.readbyqxmd.com/read/28483592/erectile-dysfunction-in-wistar-audiogenic-rats-war-is-associated-with-increased-cavernosal-contraction-and-decreased-nnos-protein-expression
#20
Fernanda Luciano Rodrigues, Rafael S Fais, Marília G A G Pereira, Norberto Garcia-Cairasco, Rita C Tostes, Fernando S Carneiro
OBJECTIVE: To test the hypothesis that naïve Wistar audiogenic rats (WAR) display ED, which is associated with increased sympathetic-mediated contractile tone and/or decreased NO-mediated relaxation responses of the cavernous tissue. METHODS: Changes in the ratio of the maximal intracavernosal pressure/mean arterial pressure (ICP/MAP) after electrical stimulation of the right major pelvic ganglion were determined in vivo. Cavernosal contractility was induced by electrical field stimulation (EFS) and phenylephrine...
May 5, 2017: Urology
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