keyword
MENU ▼
Read by QxMD icon Read
search

Fasudil

keyword
https://www.readbyqxmd.com/read/29033348/design-and-synthesis-of-benzimidazole-based-rho-kinase-inhibitors-for-the-treatment-of-glaucoma
#1
Vasudha Abbhi, Lovneet Saini, Srishti Mishra, Gautam Sethi, Alan Prem Kumar, Poonam Piplani
Rho kinase inhibitors (ROCK II) play a key role in glaucoma management attributed to their IOP lowering ability and neuroprotective effects. In the present study, a series of novel benzimidazole derivatives (9a-m) has been synthesized and evaluated for their IOP lowering, Rho kinase inhibitory and antioxidant properties. The synthesized compounds were found to be lipophilic and showed a significant IOP lowering effect both in the treated and the contralateral eye comparable to the reference standard fasudil...
October 4, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29029794/rho-kinase-inhibition-reverses-impaired-ca-2-handling-and-associated-left-ventricular-dysfunction-in-pressure-overload-induced-cardiac-hypertrophy
#2
Yusuf Olgar, Murat Cenk Celen, Bilge Eren Yamasan, Nihal Ozturk, Belma Turan, Semir Ozdemir
Recent studies have implicated a relationship between RhoA/ROCK activity and defective Ca(2+) homeostasis in hypertrophic hearts. This study investigated molecular mechanism underlying ROCK inhibition-mediated cardioprotection against pressure overload-induced cardiac hypertrophy, with a focus on Ca(2+) homeostasis. Cardiac hypertrophy model was established by performing transverse aortic constriction (TAC) in 8-week-old male rats. Groups were assigned as SHAM, TAC and TAC+Fas (rats undergoing TAC and treated with fasudil)...
November 2017: Cell Calcium
https://www.readbyqxmd.com/read/28993291/pak4-crystal-structures-suggest-unusual-kinase-conformational-movements
#3
Eric Y Zhang, Byung Hak Ha, Titus J Boggon
In order for protein kinases to exchange nucleotide they must open and close their catalytic cleft. These motions are associated with rotations of the N-lobe, predominantly around the 'hinge region'. We conducted an analysis of 28 crystal structures of the serine-threonine kinase, p21-activated kinase 4 (PAK4), including three newly determined structures in complex with staurosporine, FRAX486, and fasudil (HA-1077). We find an unusual motion between the N-lobe and C-lobe of PAK4 that manifests as a partial unwinding of helix αC...
October 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28989085/ferulic-acid-relaxed-rat-aortic-small-mesenteric-and-coronary-arteries-by-blocking-voltage-gated-calcium-channel-and-calcium-desensitization-via-dephosphorylation-of-erk1-2-and-mypt1
#4
Zhong-Yan Zhou, Jia-Qi Xu, Wai-Rong Zhao, Xin-Lin Chen, Yu Jin, Nuo Tang, Jing-Yi Tang
Ferulic acid, a natural ingredient presents in several Chinese Materia Medica such as Radix Angelicae Sinensis, has been identified as an important multifunctional and physiologically active small molecule. However, its pharmacological activity in different blood vessel types and underlying mechanisms are unclear. The present study was to investigate the vascular reactivity and the possible action mechanism of FA on aorta, small mesenteric arteries and coronary arteries isolated from Wistar rats. We found FA dose-dependently relieved the contraction of aorta, small mesenteric arteries and coronary arteries induced by different contractors, U46619, phenylephrine (Phe) and KCl...
October 6, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28972449/targeting-rock-activity-to-disrupt-and-prime-pancreatic-cancer-for-chemotherapy
#5
Claire Vennin, Nicola Rath, Marina Pajic, Michael F Olson, Paul Timpson
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease; the identification of novel targets and development of effective treatment strategies are urgently needed to improve patient outcomes. Remodeling of the pancreatic stroma occurs during PDAC development, which drives disease progression and impairs responses to therapy. The actomyosin regulatory ROCK1 and ROCK2 kinases govern cell motility and contractility, and have been suggested to be potential targets for cancer therapy, particularly to reduce the metastatic spread of tumor cells...
October 3, 2017: Small GTPases
https://www.readbyqxmd.com/read/28968596/resveratrol-inhibits-the-epidermal-growth-factor-induced-migration-of-osteoblasts-the-suppression-of-sapk-jnk-and-akt
#6
Tetsu Kawabata, Haruhiko Tokuda, Kazuhiko Fujita, Shingo Kainuma, Go Sakai, Rie Matsushima-Nishiwaki, Osamu Kozawa, Takanobu Otsuka
BACKGROUND/AIMS: Resveratrol is a polyphenol enriched in the skins of grapes and berries, that shows various beneficial effects for human health. In the present study, we investigated the mechanism behind the epidermal growth factor (EGF)-induced migration of osteoblast-like MC3T3-E1 cells, and the effect of resveratrol on this cell migration. METHODS: The cell migration was examined using Boyden chamber, and phosphorylation of each kinase was analyzed by Western blotting...
October 2, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28963443/fasudil-alleviates-lps-induced-lung-injury-by-restoring-aquaporin-5-expression-and-inhibiting-inflammation-in-lungs
#7
Jing-Jing Wang, Hui Kong, Jian Xu, Yan-Li Wang, Hong Wang, Wei-Ping Xie
Fasudil, a selective rho kinase (ROCK) inhibitor, has been reported to play a beneficial role in systemic?inflammation?in acute?lung injury, but its mechanism for ameliorating pulmonary edema and inflammation remains unclear. Using hematoxylin-and-eosin (HE) staining, immunohistochemistry, enzyme-linked immunosorbent assay, quantitative real time PCR and Western blotting, we found that fasudil attenuated LPS-induced lung injury, decreased lung edema, and suppressed inflammatory responses including leukocyte infiltration and IL-6 production...
September 30, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28957641/a-screening-system-for-evaluating-cell-extension-formation-collagen-compaction-and-degradation-in-drug-discovery
#8
Asuka Yuda, Christopher A McCulloch
The generation of cell extensions is critical for matrix remodeling in tissue invasion by cancer cells, but current methods for identifying molecules that regulate cell extension formation and matrix remodeling are not well adapted for screening purposes. We applied a grid-supported, floating collagen gel system (~100 Pa stiffness) to examine cell extension formation, collagen compaction, and collagen degradation in a single assay. With the use of cultured diploid fibroblasts, a fibroblast cell line, and two cancer cell lines, we found that compared with attached collagen gels (~2800 Pa), the mean number and length of cell extensions were respectively greater in the floating gels...
September 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28929640/rho-kinase-inhibitor-fasudil-attenuates-contrast-induced-acute-kidney-injury
#9
Yiming Wang, Hao Zhang, Zhijian Yang, Dengshun Miao, Dingguo Zhang
In this study, we tested the hypothesis that fasudil, a Rho kinase inhibitor, would protect against contrast-induced acute kidney injury (CI-AKI) in a mouse model and attempted to elucidate the mechanism involved. Mice subjected to unilateral ligation of the left anterior renal pedicle were divided into four groups: (1) control group, (2) CI-AKI induced by contrast media (CM group), (3) CI-AKI plus low-dose fasudil (LD group) and (4) CI-AKI plus high-dose fasudil (HD group). Animals from groups 2-4 received iodixanol (4...
September 19, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28916199/erk-and-rock-functionally-interact-in-a-signaling-network-that-is-compensationally-upregulated-in-spinal-muscular-atrophy
#10
Niko Hensel, Svetlana Baskal, Lisa Marie Walter, Hella Brinkmann, Manuela Gernert, Peter Claus
Spinal Muscular Atrophy (SMA) is a motoneuron disease caused by low levels of functional survival of motoneuron protein (SMN). Molecular disease mechanisms downstream of functional SMN loss are still largely unknown. Previous studies suggested an involvement of Rho kinase (ROCK) as well as the extracellular signal-regulated kinases (ERK) pathways in the pathomechanism. Both pathways are bi-directionally linked and inhibit each other. Thus, we hypothesize that both pathways regulate SMA pathophysiology in vivo in a combined manner rather than acting separately...
September 12, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28885682/selective-targeting-of-m-type-potassium-channel-kv7-4-demonstrates-its-key-role-in-regulating-of-dopaminergic-neuronal-excitability-and-depression-like-behaviour
#11
Li Li, Hui Sun, Jie Ding, Chenxu Niu, Min Su, Ludi Zhang, Yingmin Li, Chuan Wang, Nikita Gamper, Xiaona Du, Hailin Zhang
BACKGROUND AND PURPOSE: The mesolimbic dopamine (DA) system originating in the ventral tegmental area (VTA) is implicated in the development of depression, and firing patterns of VTA DA neurons are key determinants in this process. Here, we describe a crucial role of the M-type potassium channel Kv7.4 in modulation of VTA DA neuronal excitability and in the development of depressive behaviour in mice. EXPERIMENTAL APPROACH: We used Kv7.4 knock-out mice and a social defeat model of depression in combination with various electrophysiological techniques (patch clamp recording and in vivo single unit recordings), immunohistochemistry, single-cell PCR and behavioural analyses (social interaction time and glucose preference tests) to investigate VTA circuits involved in development of depression-like behaviour...
September 8, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28878396/rhoa-rock-inhibition-reverses-synaptic-remodeling-and-motor-and-cognitive-deficits-caused-by-traumatic-brain-injury
#12
Shalaka Mulherkar, Karen Firozi, Wei Huang, Mohammad Danish Uddin, Raymond J Grill, Mauro Costa-Mattioli, Claudia Robertson, Kimberley F Tolias
Traumatic brain injury (TBI) causes extensive neural damage, often resulting in long-term cognitive impairments. Unfortunately, effective treatments for TBI remain elusive. The RhoA-ROCK signaling pathway is a potential therapeutic target since it is activated by TBI and can promote the retraction of dendritic spines/synapses, which are critical for information processing and memory storage. To test this hypothesis, RhoA-ROCK signaling was blocked by RhoA deletion from postnatal neurons or treatment with the ROCK inhibitor fasudil...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28841710/inhibition-of-rock1-kinase-modulates-both-tumor-cells-and-stromal-fibroblasts-in-pancreatic-cancer
#13
Clifford J Whatcott, Serina Ng, Michael T Barrett, Galen Hostetter, Daniel D Von Hoff, Haiyong Han
ROCK, or Rho-associated coiled coil-containing protein kinase, is a member of the AGC kinase family and has been shown to play a role in cell migration, ECM synthesis, stress-fiber assembly, and cell contraction. Increased ROCK expression has been reported in multiple pathological conditions, including cancer. Here, we report increased expression of ROCK 1 in pancreatic tumor epithelial cells as well as in cancer associated fibroblasts (CAF). In our analysis, 62% of tumor samples exhibited ≥2+ in staining intensity by IHC analysis, versus 40% of adjacent normal tissue samples (P<0...
2017: PloS One
https://www.readbyqxmd.com/read/28821742/rock-1-mediates-diabetes-induced-retinal-pigment-epithelial-and-endothelial-cell-blebbing-contribution-to-diabetic-retinopathy
#14
Pierre-Raphaël Rothschild, Sawsen Salah, Marianne Berdugo, Emmanuelle Gélizé, Kimberley Delaunay, Marie-Christine Naud, Christophe Klein, Alexandre Moulin, Michèle Savoldelli, Ciara Bergin, Jean-Claude Jeanny, Laurent Jonet, Yvan Arsenijevic, Francine Behar-Cohen, Patricia Crisanti
In diabetic retinopathy, the exact mechanisms leading to retinal capillary closure and to retinal barriers breakdown remain imperfectly understood. Rho-associated kinase (ROCK), an effector of the small GTPase Rho, involved in cytoskeleton dynamic regulation and cell polarity is activated by hyperglycemia. In one year-old Goto Kakizaki (GK) type 2 diabetic rats retina, ROCK-1 activation was assessed by its cellular distribution and by phosphorylation of its substrates, MYPT1 and MLC. In both GK rat and in human type 2 diabetic retinas, ROCK-1 is activated and associated with non-apoptotic membrane blebbing in retinal vessels and in retinal pigment epithelium (RPE) that respectively form the inner and the outer barriers...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28820432/rho-kinase-blockade-attenuates-podocyte-apoptosis-by-inhibiting-the-notch-signaling-pathway-in-diabetic-nephropathy
#15
Keiichiro Matoba, Daiji Kawanami, Yosuke Nagai, Yusuke Takeda, Tomoyo Akamine, Sho Ishizawa, Yasushi Kanazawa, Tamotsu Yokota, Kazunori Utsunomiya
Podocyte apoptosis is a key process in the onset of diabetic nephropathy. A significant body of evidence shows that the Notch signaling pathway plays a central role in this process. We found that Rho-kinase mediates transforming growth factor β (TGF-β)-induced Notch ligand Jag1 expression. Importantly, TGF-β-mediated podocyte apoptosis was attenuated by Rho-kinase inhibition. Mechanistically, Rho-kinase regulated Jag1 induction via the extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) but not Smad pathways...
August 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28820400/alteration-in-expressions-of-rhoa-and-rho-kinases-during-pregnancy-in-rats-their-roles-in-uterine-contractions-and-onset-of-labour
#16
D Domokos, E Ducza, G Falkay, R Gaspar
Activation of RhoA and Rho-associated kinases (ROCKs) is known to play a pivotal role in the regulation of smooth muscle contraction via phosphorylation of myosin-light chain and myosin phosphatase. There are few data on the RhoA and ROCKs expression levels in rat uteri. Therefore, our aim was to investigate the mRNA and protein concentration of RhoA and ROCKs in rat uterus during pregnancy, during parturition and post-partum using real time PCR and Western blot analysis. The other purpose was to evaluate the effects of the ROCK (Y-27632, fasudil and RKI 1441) and RhoA inhibitors (simvastatin) on uterine contractility in isolated organ bath experiments...
June 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28782712/effects-of-fasudil-on-pulmonary-hypertension-in-clinical-practice
#17
REVIEW
Yiqing Zhang, Shangjie Wu
Pulmonary hypertension (PH) is a pathophysiologic disorder that may involve multiple clinical conditions and can complicate the majority of cardiovascular and respiratory diseases. The presence of PH is associated with worse outcomes, but the efficacy of current therapy is still unsatisfactory. Because Rho-kinase (ROCK) plays an important role in the pathogenesis of PH, the ROCK inhibitor fasudil is expected to contribute to PH treatment. In animal models of PH, fasudil reduced pulmonary artery pressure (PAP) and improved survival...
October 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28781824/effectiveness-of-continuous-low-dose-fasudil-on-refractory-coronary-vasospasm-subsequent-to-cardiopulmonary-arrest
#18
Daisuke Ooshiro, Satoshi Yamaguchi, Masanori Kakazu, Osamu Arasaki
Refractory coronary vasospasm subsequent to reperfusion, such as cardiopulmonary resuscitation or revascularization, for myocardial infarction may respond to fasudil in the superacute phase. Continuous low-dose fasudil administration should be an option for refractory coronary vasospastic angina (VSA).
August 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28741985/the-influence-of-fasudil-on-renal-proximal-tubular-cell-epithelial-mesenchymal-transition-induced-by-parathormone
#19
Ziqing Gao, Weiping Zhu, Hua Zhang, Zhonghe Li, Tongxia Cui
BACKGROUND: Renal fibrosis is a common pathway through which a variety of chronic kidney diseases progress to end-stage renal disease. Epithelial-mesenchymal transition (EMT) of renal proximal tubular cells is one of the most important factors in renal fibrosis. This study investigates if fasudil could influence EMT of renal proximal tubular cells. METHODS: HK-2 cells in passage 3-4 were used for all experiments. The cells were divided into five groups and treated with different concentrations of PTH and then observe cellular morphological changes at 0, 24 and 48 h using an inverted microscope and investigate the expression of the epithelial cell marker E-cadherin and the renal fibroblast marker α-smooth muscle actin (α-SMA)...
November 2017: Renal Failure
https://www.readbyqxmd.com/read/28739304/role-of-nadphox-rho-kinase-signaling-in-the-cyclosporine-nsaids-interactions-on-blood-pressure-and-baroreflexes-in-female-rats
#20
Hanan M El-Gowelli, Karim S Ibrahim, Ahmed F El-Yazbi, Mahmoud M El-Mas
AIMS: The hypertensive effect of the immunosuppressant drug cyclosporine (CSA) is paralleled, and probably triggered, by impaired arterial baroreceptor sensitivity (BRS). Here we asked if these effects of CSA are influenced by co-administration of nonsteroidal antiinflammatory drugs (NSAIDs) and if the oxidative NADPH-oxidase (NADPHox)/Rho-kinase (ROCK) pathway mediates this interaction. MATERIALS AND METHODS: Female rats were treated for 10days with CSA (25mg/kg/day), diclofenac (DIC, COX-1/COX-2 inhibitor, 1mg/kg/day), celecoxib (COX-2 inhibitor, 10mg/kg/day), or their combinations...
July 21, 2017: Life Sciences
keyword
keyword
39154
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"