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https://www.readbyqxmd.com/read/29451818/overexpression-of-heart-specific-small-subunit-of-myosin-light-chain-phosphatase-results-in-heart-failure-and-conduction-disturbance
#1
Takuro Arimura, Antoine Muchir, Masayoshi Kuwahara, Sachio Morimoto, Taisuke Ishikawa, Cheng-Kun Du, Dong-Yun Zhan, Shu Nakao, Noboru Machida, Ryo Tanaka, Yoshihisa Yamane, Takeharu Hayashi, Akinori Kimura
Mutations in genes encoding components of sarcomere cause cardiomyopathy, which is often associated with abnormal Ca 2+ sensitivity of muscle contraction. We previously showed that a heart-specific myosin light chain phosphatase small subunit, hHS-M 21 , increases the Ca 2+ -sensitivity of muscle contraction. The aim of this study was to investigate the function of hHS-M 21 in vivo and the causative role of abnormal Ca 2+ sensitivity in cardiomyopathy. We generated transgenic (Tg) mice with cardiac-specific overexpression of hHS-M 21 ...
February 16, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29448133/exposure-to-the-rock-inhibitor-fasudil-promotes-gliogenesis-of-neural-stem-cells-in-vitro
#2
Zubair Ahmed Nizamudeen, Lisa Chakrabarti, Virginie Sottile
Fasudil is a clinically approved Rho-associated protein kinase (ROCK) inhibitor that has been used widely to treat cerebral consequences of subarachnoid hemorrhage. It is known to have a positive effect on animal models of neurological disorders including Parkinson's disease and stroke. However, its cellular effect on progenitor populations and differentiation is not clearly understood. While recent studies suggest that fasudil promotes the mobilization of neural stem cells (NSCs) from the subventricular zone in vivo and promotes the differentiation of the C17...
February 6, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29440699/vascular-dysfunction-in-obese-diabetic-db-db-mice-involves-the-interplay-between-aldosterone-mineralocorticoid-receptor-and-rho-kinase-signaling
#3
Aurelie Nguyen Dinh Cat, Glaucia E Callera, Malou Friederich-Persson, Ana Sanchez, Maria Gabriela Dulak-Lis, Sofia Tsiropoulou, Augusto C Montezano, Ying He, Ana M Briones, Frederic Jaisser, Rhian M Touyz
Activation of aldosterone/mineralocorticoid receptors (MR) has been implicated in vascular dysfunction of diabetes. Underlying mechanisms are elusive. Therefore, we investigated the role of Rho kinase (ROCK) in aldosterone/MR signaling and vascular dysfunction in a model of diabetes. Diabetic obese mice (db/db) and control counterparts (db/+) were treated with MR antagonist (MRA, potassium canrenoate, 30 mg/kg/day, 4 weeks) or ROCK inhibitor, fasudil (30 mg/kg/day, 3 weeks). Plasma aldosterone was increased in db/db versus db/+...
February 13, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29440458/macrophage-targeting-fasudil-treatment-protects-liver-from-the-ischemia-reperfusion-injury-by-promoting-m2-macrophage-polarization
#4
Yingli Xie, Di Zhao, Pingshuan Dong, Lihong Lai
Macrophages play essential roles in the generation and resolution of inflammation. Ischemia-reperfusion injury (IRI) triggers a systemic inflammatory response and leads to cellular injury and organ failure. During surgical procedures of the liver, such as hepatic resection and liver transplantation, IRI leads to the dysfunction of the liver. Rho-associated protein kinase (ROCK) inhibitors were reported protecting the liver from IRI. However, the systematic administration of ROCK inhibitors causes severe hypotension...
February 12, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29416017/fasudil-increases-temozolomide-sensitivity-and-suppresses-temozolomide-resistant-glioma-growth-via-inhibiting-rock2-abcg2
#5
Xin Zhang, Xiuting Liu, Wei Zhou, Mengdi Yang, Yang Ding, Qing Wang, Rong Hu
Resistance to temozolomide (TMZ) is a major clinical challenge in glioma treatment, but the mechanisms of TMZ resistance are poorly understood. Here, we provided evidence that ROCK2 acted redundantly to maintain resistance of TMZ in TMZ-resistant gliomas, and as a ROCK2 phosphorylation inhibitor, fasudil significantly suppressed proliferation of TMZ-resistant gliomas in vivo and vitro via enhancing the chemosensitivity of TMZ. Additionally, the membrane translocation of ABCG2 was decreased with fasudil by ROCK2/moesin pathway...
February 7, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29383848/higher-ca2-sensitivity-of-arterial-contraction-in-1-week-old-rats-is-due-to-a-greater-rho-kinase-activity
#6
S V Mochalov, N V Tarasova, T V Kudryashova, D K Gaynullina, V U Kalenchuk, A S Borovik, A V Vorotnikov, O S Tarasova, R Schubert
AIM: During early postnatal development, arterial contraction depends less on Ca2+ -signalling pathways but more on changes in Ca2+ -sensitivity compared to adult animals. Whether this difference is related to Rho-kinase, one of the major players affecting Ca2+ -sensitivity, is unknown for intact vessels. Thus, we tested the hypothesis that Rho-kinase critically contributes to the higher Ca2+ -sensitivity of contraction in intact arteries of 1-week old rats. METHODS: We studied 1-week-old, 4-5-week-old and 10-12-week-old rats performing isometric myography, Ca2+ -fluorimetry and Western blotting using intact saphenous arteries and arterial pressure measurements under urethane anesthesia...
January 31, 2018: Acta Physiologica
https://www.readbyqxmd.com/read/29382415/-fasudil-improves-cognition-of-app-ps1-transgenic-mice-via-inhibiting-the-activation-of-microglia-and-shifting-microglia-phenotypes-from-m1-to-m2
#7
Jiezhong Yu, Qingfang Gu, Yuqing Yan, Hongqiang Yu, Minfang Guo, Chunyun Liu, Guobin Song, Zhi Chai, Qing Wang, Baoguo Xiao, Hanting Zhang, Yuqiang Jiang, Cungen Ma
Objective To examine the regulatory effects of Rho kinase inhibitor fasudil on cognition and microglia polarization in APP/PS1 transgenic (APP/PS1 Tg) mice, a widely used model of Alzheimer's disease (AD). Methods Male APP/PS1 Tg mice at 8 months of age were randomly divided into two groups: Fasudil (25 mg/kg) and saline, i.p., once daily for 2 months; age- and gender-matched wild type (WT) mice without treatment were used as the controls. The Morris water maze (MWM) test was applied to examine spatial cognition of mice...
December 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/29373038/actin-polymerization-contributes-to-enhanced-pulmonary-vasoconstrictor-reactivity-following-chronic-hypoxia
#8
Laura Weise-Cross, Michelle Sands, Joshua R Sheak, Brad R S Broughton, Jessica B Snow, Laura V Gonzalez Bosc, Nikki L Jernigan, Benjimen R Walker, Thomas C Resta
Chronic hypoxia (CH) augments basal and endothelin 1 (ET-1)-induced pulmonary vasoconstrictor reactivity through reactive oxygen species (ROS) generation and RhoA/Rho kinase (ROCK)-dependent myofilament Ca2+ sensitization. Because ROCK promotes actin polymerization and the actin cytoskeleton regulates smooth muscle tension, we hypothesized that actin polymerization is required for enhanced basal and ET-1-dependent vasoconstriction following CH. To test this hypothesis, both endpoints were monitored in pressurized, endothelium-disrupted pulmonary arteries (4th-5th order) from control and CH (4 wk at 0...
January 26, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29337194/fasudil-ameliorates-the-ischemia-reperfusion-oxidative-injury-in-rat-hearts-through-suppression-of-myosin-regulatory-light-chain-nadph-oxidase-2-pathway
#9
Yi-Shuai Zhang, Li-Jing Tang, Hua Tu, Shi-Jing Wang, Bin Liu, Xiao-Jie Zhang, Nian-Sheng Li, Xiu-Ju Luo, Jun Peng
Fasudil is a potent Rho-kinase (ROCK) inhibitor and can relax smooth muscle or cardiac muscle contraction through decreasing the phosphorylation level of myosin regulatory light chain (p-MLC20 or p-MLC2v), while p-MLC2v can function as a transcription factor to promote the NADPH oxidase 2 (NOX2) expression in rat hearts subjected to ischemia/reperfusion (I/R). This study aims to explore whether fasudil can protect the rat hearts against I/R oxidative injury through suppressing NOX2 expression via reduction of p-MLC2v level...
January 11, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29336470/tnf-%C3%AE-induces-drp1-mediated-mitochondrial-fragmentation-during-inflammatory-cardiomyocyte-injury
#10
Yue-Liang Shen, Ying-Zhou Shi, Gai-Ge Chen, Lin-Lin Wang, Ming-Zhi Zheng, Hong-Feng Jin, Ying-Ying Chen
Dynamin-related peptide 1 (Drpl)-mediated mitochondrial fission is an important process associated with cardiac dysfunction under different pathological conditions. The aim of the present study was to investigate the expression of Drpl during inflammatory myocardial injury. Sprague‑Dawley rats were treated intraperitoneally with lipopolysaccharides (LPS). Furthermore, cultured H9C2 cardiomyocytes were treated with LPS, interleukin‑6 (IL‑6) and tumor necrosis factor‑α (TNF‑α). Total and mitochondrial proteins were isolated from the heart tissue of rats and from the H9C2 cardiomyocytes...
January 15, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29323739/fasudil-alleviates-pressure-overload-induced-heart-failure-by-activating-nrf2-mediated-antioxidant-responses
#11
Peng Guan, Yingran Liang, Na Wang
The RhoA/Rho-kinase cascade plays an important role in many aspects of cardiovascular function. This study aims to investigate the protective effects of fasudil, a Rho-kinase inhibitor, on pressure overload induced heart failure in rats. Pressure overload induced heart failure was induced in SD rats by banding the abdominal aorta for 8 weeks. The rats were divided into four groups: Sham, TAC, TAC plus low dose of fasudil and TAC plus high dose of fasudil group. Low dose and high dose fasudil were 5 mg/kg/day and 10 mg/kg/day respectively...
January 11, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29283979/inhibition-of-rho-kinase-by-fasudil-attenuates-ischemic-lung-injury-after-cardiac-arrest-in-rats
#12
Jian Wei, Peng Wang, Yi Li, Qingli Dou, Jiali Lin, Wuyuan Tao, Jinle Lin, Xuan Fu, Zitong Huang, Wenwu Zhang
Lung injury is a common complication after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR), and Rho kinase (ROCK) may be involved in the process of this injury. In this study, we aimed to study the effects of ROCK inhibition by fasudil on lung injury induced by asphyxial CA and CPR in rats. A total of 130 rats were randomized into three groups: Sham, Control, and Fasudil intervention group. Animals in the Fasudil intervention group were intraperitoneally administered with 10 mg/kg of the drug, 1 h before inducing CA...
December 27, 2017: Shock
https://www.readbyqxmd.com/read/29277889/rhoa-stimulated-intra-capillary-morphology-switch-facilitates-the-arrest-of-individual-circulating-tumor-cells
#13
Xi Huang, Yu Yang, Yuwei Zhao, Cao Dan, Xiaolin Ai, Anqi Zeng, Maling Gou, Lulu Cai, Hanshuo Yang, Chengjian Zhao
Metastasis is the primary cause of death for most cancer patients. Hematogenous arrest of circulating tumor cells (CTCs) is an essential prerequisite for metastases formation. Using transparent transgenic zebrafish (kdrl:eGFP; Casper), together with resonant laser scanning confocal microscopy, we tracked the fate of CTCs in vivo in the blood circulation for days. We found the intra-capillary morphology-switch (ICMS) of individual CTCs from strip to sphere was necessary for their intravascular arrests. Further genetic and pharmacological inhibition experiments indicated that the RhoA signaling was necessary for ICMS and the arrest of CTCs...
December 26, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29202196/effects-of-dlc1-deficiency-on-endothelial-cell-contact-growth-inhibition-and-angiosarcoma-progression
#14
David Sánchez-Martín, Atsushi Otsuka, Kenji Kabashima, Taekyu Ha, Dunrui Wang, Xiaolan Qian, Douglas R Lowy, Giovanna Tosato
Background: Deleted in Liver Cancer 1 (DLC1) is a tumor suppressor gene frequently deleted in cancer. However, DLC1 is not known to be deleted in angiosarcoma, an aggressive malignancy of endothelial cell derivation. Additionally, the physiologic functions of DLC1 protein in endothelial cells are poorly defined. Methods: We investigated the effects of shRNA-induced DLC1 depletion in endothelial cells. Cell growth was measured by 3H thymidine incorporation, IncuCyte imaging, and population doublings; cell death by cell cycle analysis; gene expression by Affimetrix arrays and quantitative polymerase chain reaction; NF-κB activity by reporter assays; and protein levels by immunoblotting and immunofluorescence staining...
November 30, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29187752/inhibiting-rho-kinase-promotes-goal-directed-decision-making-and-blocks-habitual-responding-for-cocaine
#15
Andrew M Swanson, Lauren M DePoy, Shannon L Gourley
The prelimbic prefrontal cortex is necessary for associating actions with their consequences, enabling goal-directed decision making. We find that the strength of action-outcome conditioning correlates with dendritic spine density in prelimbic cortex, suggesting that new action-outcome learning involves dendritic spine plasticity. To test this, we inhibited the cytoskeletal regulatory factor Rho kinase. We find that the inhibitor fasudil enhances action-outcome memory, resulting in goal-directed behavior in mice that would otherwise express stimulus-response habits...
November 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/29162447/co-administration-of-liposomal-fasudil-and-tissue-plasminogen-activator-ameliorated-ischemic-brain-damage-in-occlusion-model-rats-prepared-by-photochemically-induced-thrombosis
#16
Tatsuya Fukuta, Yosuke Yanagida, Tomohiro Asai, Naoto Oku
Delivery of neuroprotectants with liposomes has been shown to be effective for the treatment of ischemic stroke. We have recently revealed that intravenous administration of liposomal fasudil (Fasudil-Lip), a Rho-kinase inhibitor, prior to thrombolysis with tissue plasminogen activator (t-PA) can extend the narrow therapeutic time window (TTW) of t-PA. In the present study, we examined the influence of t-PA treatment on liposomal accumulation into the ischemic region and cerebroprotective effect of combined treatment with Fasudil-Lip and t-PA performed at the same timing after the onset of ischemia in middle cerebral artery occlusion (MCAO) prepared by photochemically induced thrombosis...
January 1, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29135354/depression-following-traumatic-brain-injury-in-mice-is-associated-with-down-regulation-of-hippocampal-astrocyte-glutamate-transporters-by-thrombin
#17
Chun-Shu Piao, Ashley L Holloway, Sue Hong-Routson, Mark S Wainwright
Depression after traumatic brain injury (TBI) is common but the mechanisms by which TBI causes depression are unknown. TBI decreases glutamate transporters GLT-1 and GLAST and allows extravasation of thrombin. We examined the effects of thrombin on transporter expression in primary hippocampal astrocytes. Application of a PAR-1 agonist caused down-regulation of GLT-1, which was prevented by inhibition of Rho kinase (ROCK). To confirm these mechanisms in vivo, we subjected mice to closed-skull TBI. Thrombin activity in the hippocampus increased one day following TBI...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29119680/nicorandil-regulates-the-macrophage-skewing-and-ameliorates-myofibroblasts-by-inhibition-of-rhoa-rho-kinase-signalling-in-infarcted-rats
#18
Tsung-Ming Lee, Shinn-Zong Lin, Nen-Chung Chang
We have demonstrated that ATP-sensitive potassium (KATP ) channel agonists attenuated fibrosis; however, the mechanism remained unclear. Since RhoA has been identified as a mediator of cardiac fibrosis, we sought to determine whether the anti-fibrotic effects of KATP channel agonists were mediated via regulating macrophage phenotype and fibroblast differentiation by a RhoA/RhoA-kinase-dependent pathway. Wistar male rats after induction of myocardial infarction were randomized to either vehicle, nicorandil, an antagonist of KATP channel glibenclamide, an antagonist of ROCK fasudil, or a combination of nicorandil and glibenclamide or fasudil and glibenclamide starting 24 hrs after infarction...
November 9, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29099428/neuroprotective-effects-of-fasudil-a-rho-kinase-inhibitor-after-spinal-cord-ischemia-and-reperfusion-in-rats
#19
Masahiko Ohbuchi, Tetsu Kimura, Toshiaki Nishikawa, Takashi Horiguchi, Masayuki Fukuda, Yoko Masaki
BACKGROUND: Excessive Rho/Rho-kinase pathway activation occurs subsequent to stroke. We examined the neuroprotective effects of pre- and posttreatment with fasudil (a Rho-kinase inhibitor) in a rat transient spinal cord ischemia-reperfusion model under normothermic conditions. METHODS: After approval by our animal research committee, male Sprague-Dawley rats were assigned to 1 of 6 groups: pre- and postcontrol (C); pre- and postfasudil (F); and pre- and postsham (S)...
November 1, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/29070466/-rhoa-rho-kinase-contributes-to-chronic-pain-following-thoracotomy-by-up-regulating-glutaminase-1-expression-in-rat-spinal-dorsal-cord
#20
Zi-Yan Liu, Hai-Tang Wang, Jing Tang, Zai-Sheng Qin
OBJECTIVE: To investigate whether RhoA/Rho-kinase contributes to the occurrence of chronic post-thoracotomy pain (CPSP) by up regulation of glutaminase 1 (GLS1) expression in the spinal dorsal cord. METHODS: Twenty five male Sprague Dawley (SD) rats were divided into control group (n=5) and model group (n=20). The rats in the model group were randomized into two sub groups (n=10) for observation on day 10 and day 21 after thoracotomy, and each group was further divided into CPSP and non CPSP groups according to the behavioral test results...
October 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
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