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https://www.readbyqxmd.com/read/28220212/rho-kinase-inhibition-ameliorates-cyclophosphamide-induced-cystitis-in-rats
#1
Andrzej Wróbel, Urszula Doboszewska, Ewa Rechberger, Karol Rojek, Anna Serefko, Ewa Poleszak, Krystyna Skalicka-Woźniak, Jarosław Dudka, Piotr Wlaź
Hemorrhagic cystitis often develops in patients treated with cyclophosphamide (CYP). Studies have indicated that Rho kinase (ROCK) inhibitors may suppress detrusor overactivity symptoms and possess anti-inflammatory properties. The aim of the present study was to investigate whether inhibition of ROCK reduces cystometric and histopathological changes associated with CYP-induced cystitis. The rats received GSK 269962, a ROCK inhibitor, at a dose of 30 mg/kg daily, or vehicle for 7 days. Then, acute chemical cystitis leading to bladder overactivity was induced by CYP injection (200 mg/kg i...
February 21, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28208020/graphene-oxide-induced-perturbation-to-plasma-membrane-and-cytoskeletal-meshwork-sensitize-cancer-cells-to-chemotherapeutic-agents
#2
Jianqiang Zhu, Ming Xu, Ming Gao, Zhihong Zhang, Yong Xu, Tian Xia, Sijin Liu
The outstanding physicochemical properties endow graphene materials (e.g., graphene oxide, GO) with beneficial potentials in diverse biomedical fields such as bioimaging, drug delivery, and biomolecular detection. GO recently emerged as a chemosensitizer; however, the detailed molecular basis underlying GO-conducted sensitization and corresponding biological effects are still elusive. Based on our recent findings that GO treatment at sublethal concentrations could impair the general cellular priming state, including disorders of plasma membrane and cytoskeleton construction, we aimed here to explore the mechanism of GO as a sensitizer to make cancer cells more susceptible to chemotherapeutic agents...
February 20, 2017: ACS Nano
https://www.readbyqxmd.com/read/28205330/effect-of-matrix-stiffness-on-osteoblast-functionalization
#3
Tao Zhang, Shiyu Lin, Xiaoru Shao, Qi Zhang, Changyue Xue, Shu Zhang, Yunfeng Lin, Bofeng Zhu, Xiaoxiao Cai
OBJECTIVES: Stiffness of bone tissue differs response to its physiological or pathological status, such as osteoporosis or osteosclerosis. Consequently, the function of cells residing in bone tissue including osteoblasts (OBs), osteoclasts and osteocytes will be affected. However, to the best of our knowledge, the detailed mechanism of how extracellular matrix stiffness affects OB function remains unclear. MATERIALS AND METHODS: We conducted a study that exposed rat primary OBs to polydimethylsiloxane substrates with varied stiffness to investigate the alterations of cell morphology, osteoblastic differentiation and its potential mechanism in mechanotransduction...
February 15, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/28199964/blockade-of-rho-associated-protein-kinase-rock-inhibits-the-contractility-and-invasion-potential-of-cancer-stem-like-cells
#4
Srisathya Srinivasan, Vandhana Ashok, Sagarajit Mohanty, Alakesh Das, Sreya Das, Sushant Kumar, Shamik Sen, Rahul Purwar
Recent studies have implicated the roles of cancer stem like cells (CSCs) in cancer metastasis. However, very limited knowledge exists at the molecular and cellular level to target CSCs for prevention of cancer metastasis. In this study, we examined the roles of contractile dynamics of CSCs in cell invasion and delineated the underlying molecular mechanisms of their distinct cell invasion potential. Using de-adhesion assay and atomic force microscopy, we show that CSCs derived from melanoma and breast cancer cell lines exhibit increased contractility compared to non-CSCs across all tumor types...
February 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28197100/rho-kinase-inhibition-with-fasudil-in-the-sod1-g93a-mouse-model-of-amyotrophic-lateral-sclerosis-symptomatic-treatment-potential-after-disease-onset
#5
René Günther, Alexander Balck, Jan C Koch, Tobias Nientiedt, Michael Sereda, Mathias Bähr, Paul Lingor, Lars Tönges
Despite an improved understanding of the genetic background and the pathomechanisms of amyotrophic lateral sclerosis (ALS) no novel disease-modifying therapies have been successfully implemented in clinical routine. Riluzole still remains the only clinically approved substance in human ALS treatment with limited efficacy. We have previously identified pharmacological rho kinase (ROCK) inhibitors as orally applicable substances in SOD1.G93A transgenic ALS mice (SOD1(G93A)), which are able to extend survival time and improve motor function after presymptomatic treatment...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28191820/vascular-smooth-muscle-cell-glycocalyx-mediates-shear-stress-induced-contractile-responses-via-a-rho-kinase-rock-myosin-light-chain-phosphatase-mlcp-pathway
#6
Hongyan Kang, Jiajia Liu, Anqiang Sun, Xiao Liu, Yubo Fan, Xiaoyan Deng
The vascular smooth muscle cells (VSMCs) are exposed to interstitial flow induced shear stress that may be sensed by the surface glycocalyx, a surface layer composed primarily of proteoglycans and glycoproteins, to mediate cell contraction during the myogenic response. We, therefore, attempted to elucidate the signal pathway of the glycocalyx mechanotransduction in shear stress regulated SMC contraction. Human umbilical vein SMCs (HUVSMCs) deprived of serum for 3-4 days were exposed to a step increase (0 to 20 dyn/cm(2)) in shear stress in a parallel plate flow chamber, and reduction in the cell area was quantified as contraction...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28191463/substrate-stiffness-influences-doxorubicin-induced-p53-activation-via-rock2-expression
#7
Takahiro Ebata, Yasumasa Mitsui, Wataru Sugimoto, Miho Maeda, Keigo Araki, Hiroaki Machiyama, Ichiro Harada, Yasuhiro Sawada, Hideaki Fujita, Hiroaki Hirata, Keiko Kawauchi
The physical properties of the extracellular matrix (ECM), such as stiffness, are involved in the determination of the characteristics of cancer cells, including chemotherapy sensitivity. Resistance to chemotherapy is often linked to dysfunction of tumor suppressor p53; however, it remains elusive whether the ECM microenvironment interferes with p53 activation in cancer cells. Here, we show that, in MCF-7 breast cancer cells, extracellular stiffness influences p53 activation induced by the antitumor drug doxorubicin...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28188861/functions-of-rho-family-of-small-gtpases-and-rho-associated-coiled-coil-kinases-in-bone-cells-during-differentiation-and-mineralization
#8
REVIEW
Agnieszka Strzelecka-Kiliszek, Saida Mebarek, Monika Roszkowska, René Buchet, David Magne, Slawomir Pikula
BACKGROUND: Members of Rho-associated coiled-coil kinases (ROCKs) are effectors of Rho family of small GTPases. ROCKs have multiple functions that include regulation of cellular contraction and polarity, adhesion, motility, proliferation, apoptosis, differentiation, maturation and remodeling of the extracellular matrix (ECM). SCOPE OF THE REVIEW: Here, we focus on the action of RhoA and RhoA effectors, ROCK1 and ROCK2, in cells related to tissue mineralization: mesenchymal stem cells, chondrocytes, pre-osteoblasts, osteoblasts, osteocytes, lining cells and osteoclasts...
February 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28182100/semaphorin-3a-increases-fak-phosphorylation-at-focal-adhesions-to-modulate-mda-mb-231-cell-migration-and-spreading-on-different-substratum-concentrations
#9
Scott Gehler, Frances V Compere, Alex M Miller
Interactions between integrin-mediated adhesions and the extracellular matrix (ECM) are important regulators of cell migration and spreading. However, mechanisms by which extracellular ligands regulate cell migration and spreading in response to changes in substratum concentration are not well understood. Semaphorin 3A (Sema3A) has been shown to inhibit cell motility and alter integrin signaling in various cell types. We propose that Sema3A alters focal adhesions to modulate breast carcinoma cell migration and spreading on substrata coated with different concentrations of ECM...
2017: International Journal of Breast Cancer
https://www.readbyqxmd.com/read/28165055/human-embryonic-and-induced-pluripotent-stem-cells-maintain-phenotype-but-alter-their-metabolism-after-exposure-to-rock-inhibitor
#10
Spyros I Vernardis, Konstantinos Terzoudis, Nicki Panoskaltsis, Athanasios Mantalaris
Human pluripotent stem cells (hPSCs) are adhesion-dependent cells that require cultivation in colonies to maintain growth and pluripotency. Robust differentiation protocols necessitate single cell cultures that are achieved by use of ROCK (Rho kinase) inhibitors. ROCK inhibition enables maintenance of stem cell phenotype; its effects on metabolism are unknown. hPSCs were exposed to 10 μM ROCK inhibitor for varying exposure times. Pluripotency (TRA-1-81, SSEA3, OCT4, NANOG, SOX2) remained unaffected, until after prolonged exposure (96 hrs)...
February 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28157424/a-rho-associated-kinase-inhibitor-protects-permeability-in-a-cell-culture-model-of-ocular-disease-and-reduces-aqueous-flare-in-anterior-uveitis
#11
Hiroshi Yamada, Masahiko Yoneda, Shingo Inaguma, Masahiko Gosho, Yusuke Murasawa, Zenzo Isogai, Masahiro Zako
PURPOSE: Recent clinical and experimental studies have reported favorable results when using Rho-associated kinase (ROCK) inhibitors for ocular disease, and in cell culture. Disruption of the human, nonpigmented ciliary epithelial cells (HNPCECs) that comprise the blood-aqueous barrier (BAB) induces anterior uveitis; these cells therefore provide a useful cell model of ocular disease. In this study, we examined the effects of ROCK inhibitors in anterior uveitis and in HNPCECs. METHODS: Aqueous flare values and intraocular pressures (IOPs) were determined in patients with anterior uveitis, 2 weeks after administration of ripasudil hydrochloride hydrate, a commercial ROCK inhibitor used to treat glaucoma or ocular hypertension...
February 3, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28155615/the-protective-effect-of-dl0805-derivatives-on-pulmonary-artery-cells-and-the-underlying-mechanisms-study
#12
Tianyi Yuan, Huifang Zhang, Yucai Chen, Xiaozhen Jiao, Ping Xie, Lianhua Fang, Guanhua Du
Pulmonary hypertension (PH) is a severe disease characterized by a progressive increase in pulmonary vascular resistance, initially due to abnormal pulmonary vasoconstriction in response to endothelial and smooth muscle cells injury. The discovery of new chemical entities having a protective effect on pulmonary artery cells could be meaningful for the treatment of PH. We evaluated the protective effect of DL0805 derivatives (DL0805-1 and DL0805-2) on pulmonary artery vascular cells, including human pulmonary artery endothelial cells (HPAECs) and human pulmonary artery smooth muscle cells (HPASMCs)...
February 1, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/28135625/histone-demethylase-kdm3a-a-novel-regulator-of-vascular-smooth-muscle-cells-controls-vascular-neointimal-hyperplasia-in-diabetic-rats
#13
Jing Chen, Jing Zhang, Jian Yang, Lin Xu, Qi Hu, Changwu Xu, Shuo Yang, Hong Jiang
BACKGROUND AND AIMS: Deregulation of histone demethylase KDM3a, an important regulator for H3K9 methylation, is correlated with obesity and abnormal metabolism in rodent models. However, the function of KDM3a in vascular remodeling under diabetic condition is unknown. METHODS: Adenoviruses expressing KDM3a and lentiviruses expressing KDM3a-targeting siRNA were generated to study the role of KDM3a both in vivo and in vitro. The carotid artery balloon injury model was established in diabetic SD rats to evaluate the significance of KDM3a in vascular injury...
December 9, 2016: Atherosclerosis
https://www.readbyqxmd.com/read/28134247/cellular-mechano-environment-regulates-the-mammary-circadian-clock
#14
Nan Yang, Jack Williams, Vanja Pekovic-Vaughan, Pengbo Wang, Safiah Olabi, James McConnell, Nicole Gossan, Alun Hughes, Julia Cheung, Charles H Streuli, Qing-Jun Meng
Circadian clocks drive ∼24 h rhythms in tissue physiology. They rely on transcriptional/translational feedback loops driven by interacting networks of clock complexes. However, little is known about how cell-intrinsic circadian clocks sense and respond to their microenvironment. Here, we reveal that the breast epithelial clock is regulated by the mechano-chemical stiffness of the cellular microenvironment in primary cell culture. Moreover, the mammary clock is controlled by the periductal extracellular matrix in vivo, which contributes to a dampened circadian rhythm during ageing...
January 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/28129474/role-of-moesin-src-and-ros-in-advanced-glycation-end-product-induced-vascular-endothelial-dysfunction
#15
Wei-Jin Zhang, Pei-Xin Li, Xiao-Hua Guo, Qiao-Bing Huang
The disruption of endothelial integrity and the occurrence of angiogenesis in response to advanced glycation end products (AGEs) contribute greatly to micro- and macrovascular complications associated with diabetes mellitus (DM). Among human dermal, brain and retinal vascular endothelial cells, activation of ERM protein (Ezrin, radixin and moesin protein), moesin, by phosphorylation of Threonine 558 (Thr-558) is involved in AGE-induced hyperpermeability and angiogenesis via the Rho and Rho-associated protein kinase (Rho/ROCK) and p38 pathways...
January 27, 2017: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/28122300/y-27632-a-rho-associated-protein-kinase-inhibitor-inhibits-systemic-lupus-erythematosus
#16
Yuanyuan Wang, Yang Lu, Jixia Chai, Meiqun Sun, Xiaodong Hu, Wenxin He, Min Ge, Changhao Xie
The purpose of the present study was to evaluate whether Rho-kinase inhibition (Y-27632) modulated the expressions of nuclear factor kappaB (NF-κB) in systemic lupus erythematosus. 20 wild type mice and 20 MRL/lpr mice were applied for the research. The animals were randomly assigned to wild type, wild type+Y-27632 group, MRL/lpr group and MRL/lpr+Y-27632 group. 5mg/kg Y-27632 was intravenously injected to inhibit the ROCK expressions.Y-27632 significantly decreased the serum levels of interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α) and increased IL-10 level in serum of MRL/lpr mice...
January 22, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28117029/microrna-148a-acts-as-a-tumor-suppressor-in-osteosarcoma-via-targeting-rho-associated-coiled-coil-kinase
#17
HaiYan Yang, ZhiGang Peng, ZhenZhen Da, Xin Li, YeXiao Cheng, BinBin Tan, Xin Xiang, HaiPing Zheng, Yan Li, LanHua Chen, Ning Mo, XueXin Yan, Xiaolin Li, XiaoHua Hu
MicroRNAs (miRs) have been demonstrated to be involved in the development and progression of osteosarcoma (OS), but themolecular mechanism still remains to be fully investigated. The present study aimed to investigate the function of miR-148a in osteosarcoma, as well as the underlying mechanism. Our data showed that miR-148a was significantly downregulated in OS tissues compared to their matched adjacent normal tissues, and also in OS cell lines compared to normal human osteoblast cells. Low expression of miR-148a was significantly associated with tumor progression and poor prognosis of OS patients...
January 23, 2017: Oncology Research
https://www.readbyqxmd.com/read/28109911/rho-kinase-inhibitor-prevents-acute-injury-against-transient-focal-cerebral-ischemia-by-enhancing-the-expression-and-function-of-gaba-receptors-in-rats
#18
Lin Huang, Qin Li, Ruiting Wen, Zhiying Yu, Na Li, Liping Ma, Wanyu Feng
Studies have shown hydroxyfasudil-mediated inhibition of Rho-kinase (ROCK) has efficacy in rodent models of focal ischemia and in in vitro systems that recapitulate stroke conditions. However, the mechanisms underlying the neuroprotective effects of the ROCK inhibitor on stroke are not well understood. In this study, we examined the role of γ-aminobutyric acid (GABA) interneurons in the effects of hydroxyfasudil on transient middle cerebral artery occlusion (tMCAO) induced acute ischemia-reperfusion injury to explore the mechanisms...
January 18, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28102353/cofilin-regulates-nuclear-architecture-through-a-myosin-ii-dependent-mechanotransduction-module
#19
O'Neil Wiggan, Bryce Schroder, Diego Krapf, James R Bamburg, Jennifer G DeLuca
Structural features of the nucleus including shape, size and deformability impact its function affecting normal cellular processes such as cell differentiation and pathological conditions such as tumor cell migration. Despite the fact that abnormal nuclear morphology has long been a defining characteristic for diseases such as cancer relatively little is known about the mechanisms that control normal nuclear architecture. Mounting evidence suggests close coupling between F-actin cytoskeletal organization and nuclear morphology however, mechanisms regulating this coupling are lacking...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28101628/rho-kinase-inhibitor-fasudil-mitigates-high-cholesterol-diet-induced-hypercholesterolemia-and-vascular-damage
#20
Nibrass Taher Abdali, Awny H Yaseen, Eman Said, Tarek M Ibrahim
The current study was designed to investigate the potential beneficial therapeutic outcome of Rho kinase inhibitor (fasudil) against hypercholesterolemia-induced myocardial and vascular injury in rabbits together with diet modification. Sixteen male rabbits were randomly divided into four groups: normal control group which received standard rabbit chow, hypercholesterolemic control group, and treated groups which received cholesterol-rich rabbit chow (1.5% cholesterol) for 8 weeks. Treated groups received either fasudil (100 mg/kg/day) or rosuvastatin (2...
January 18, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
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