scholarly journals Wnt-3a and Dvl Induce Neurite Retraction by Activating Rho-Associated Kinase

2004 ◽  
Vol 24 (10) ◽  
pp. 4487-4501 ◽  
Author(s):  
Shosei Kishida ◽  
Hideki Yamamoto ◽  
Akira Kikuchi
Keyword(s):  
Neurite Outgrowth ◽  
Pc12 Cells ◽  
Mammalian Cells ◽  
Planar Cell Polarity ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Binding Domain ◽  
Serum Starvation ◽  
Neurite Retraction ◽  
Rho Kinase Inhibitor

ABSTRACT Dvl is a key protein that transmits the Wnt signal to the canonical β-catenin pathway and the noncanonical planar cell polarity (PCP) pathway. We studied the roles of Rho-associated kinase (Rho-kinase), which is activated by Dvl in the PCP pathway of mammalian cells. The expression of Dvl-1, Wnt-1, or Wnt-3a activated Rho-kinase in COS cells, and this activation was inhibited by the Rho-binding domain of Rho-kinase. The expression of Dvl-1 in PC12 cells activated Rho and inhibited nerve growth factor (NGF)-induced neurite outgrowth. This inhibition was reversed by a Rho-kinase inhibitor but not by a c-Jun N-terminal kinase inhibitor. Dvl-1 also inhibited serum starvation-dependent neurite outgrowth of N1E-115 cells, and expression of the Rho-binding domain of Rho-kinase reversed this inhibitory activity of Dvl-1. Dvl-1 mutants that did not activate Rho-kinase did not inhibit the neurite outgrowth of N1E-115 cells. Furthermore, the purified Wnt-3a protein activated Rho-kinase and inhibited the NGF-dependent neurite outgrowth of PC12 cells. Wnt-3a-dependent neurite retraction was also prevented by a Rho-kinase inhibitor and a Dvl-1 mutant that suppresses Wnt-3a-dependent activation of Rho-kinase. These results suggest that Wnt-3a and Dvl regulate neurite formation through Rho-kinase and that PC12 and N1E-115 cells are useful for analyzing the PCP pathway.

scholarly journals Myosin IIA Drives Neurite Retraction

2003 ◽  
Vol 14 (11) ◽  
pp. 4654-4666 ◽  
Author(s):  
Steven R. Wylie ◽  
Peter D. Chantler
Keyword(s):  
Antisense Oligonucleotides ◽  
Kinase Inhibitor ◽  
Neuroblastoma Cells ◽  
Rho Kinase ◽  
Myosin Isoforms ◽  
Simultaneous Application ◽  
Neurite Retraction ◽  
Rho Kinase Inhibitor ◽  
Myosin Iia ◽  
Subsequent Addition

Neuritic extension is the resultant of two vectorial processes: outgrowth and retraction. Whereas myosin IIB is required for neurite outgrowth, retraction is driven by a motor whose identity has remained unknown until now. Preformed neurites in mouse Neuro-2A neuroblastoma cells undergo immediate retraction when exposed to isoform-specific antisense oligonucleotides that suppress myosin IIB expression, ruling out myosin IIB as the retraction motor. When cells were preincubated with antisense oligonucleotides targeting myosin IIA, simultaneous or subsequent addition of myosin IIB antisense oligonucleotides did not elicit neurite retraction, both outgrowth and retraction being curtailed. Even during simultaneous application of antisense oligonucleotides against both myosin isoforms, lamellipodial spreading continued despite the complete inhibition of neurite extension, indicating an uncoupling of lamellipodial dynamics from movement of the neurite. Significantly, lysophosphatidate- or thrombin-induced neurite retraction was blocked not only by the Rho-kinase inhibitor Y27632 but also by antisense oligonucleotides targeting myosin IIA. Control oligonucleotides or antisense oligonucleotides targeting myosin IIB had no effect. In contrast, Y27632 did not inhibit outgrowth, a myosin IIB-dependent process. We conclude that the conventional myosin motor, myosin IIA, drives neurite retraction.

scholarly journals Rho Kinase Inhibitor Y-27632 Down-Regulates Norepinephrine Synthesis and Release in PC12 Cells

2009 ◽  
Vol 104 (6) ◽  
pp. 434-440 ◽  
Author(s):  
Wei-Gang Duan ◽  
Jing Shang ◽  
Zhen-Zhou Jiang ◽  
Jin-Cheng Yao ◽  
Yu Yun ◽  
...  
Keyword(s):  
Pc12 Cells ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Rho Kinase Inhibitor

scholarly journals Rho-kinase inhibitor hydroxyfasudil protects against HIV-1 Tat-induced dysfunction of tight junction and neprilysin/Aβ transfer receptor expression in mouse brain microvessels

2021 ◽  
Vol 476 (5) ◽  
pp. 2159-2170
Author(s):  
Qiangtang Chen ◽  
Yu Wu ◽  
Yachun Yu ◽  
Junxiang Wei ◽  
Wen Huang
Keyword(s):  
Tight Junction ◽  
Signaling Pathway ◽  
Mouse Brain ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Receptor Expression ◽  
Mrna Levels ◽  
Brain Microvessels ◽  
Rho Kinase Inhibitor ◽  
Hiv 1

AbstractHIV-1 transactivator protein (Tat) induces tight junction (TJ) dysfunction and amyloid-beta (Aβ) clearance dysfunction, contributing to the development and progression of HIV-1-associated neurocognitive disorder (HAND). The Rho/ROCK signaling pathway has protective effects on neurodegenerative disease. However, the underlying mechanisms of whether Rho/ROCK protects against HIV-1 Tat-caused dysfunction of TJ and neprilysin (NEP)/Aβ transfer receptor expression have not been elucidated. C57BL/6 mice were administered sterile saline (i.p., 100 μL) or Rho-kinase inhibitor hydroxyfasudil (HF) (i.p., 10 mg/kg) or HIV-1 Tat (i.v., 100 μg/kg) or HF 30 min before being exposed to HIV-1 Tat once a day for seven consecutive days. Evans Blue (EB) leakage was detected via spectrophotometer and brain slides in mouse brains. The protein and mRNA levels of zonula occludens-1 (ZO-1), occludin, NEP, receptor for advanced glycation end products (RAGE), and low-density lipoprotein receptor-related protein 1 (LRP1) in mouse brain microvessels were, respectively, analyzed by Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) analyses. Exposure of the mice to HIV-1 Tat increased the amount of EB leakage, EB fluorescence intensity, blood–brain barrier (BBB) permeability, as well as the RAGE protein and mRNA levels, and decreased the protein and mRNA levels of ZO-1, occludin, NEP, and LRP1 in mouse brain microvessels. However, these effects were weakened by Rho-kinase inhibitor HF. Taken together, these results provide information that the Rho/ROCK signaling pathway is involved in HIV-1 Tat-induced dysfunction of TJ and NEP/Aβ transfer receptor expression in the C57BL/6 mouse brain. These findings shed some light on potentiality of inhibiting Rho/Rock signaling pathway in handling HAND.

Rho kinase inhibitor for primary open-angle glaucoma and ocular hypertension

2020 ◽  
Author(s):  
Josefine Clement Freiberg ◽  
Alexander von Spreckelsen ◽  
Naira Khachatryan ◽  
Miriam Kolko ◽  
Augusto Azuara-Blanco ◽  
...  
Keyword(s):  
Ocular Hypertension ◽  
Primary Open Angle Glaucoma ◽  
Kinase Inhibitor ◽  
Open Angle Glaucoma ◽  
Rho Kinase ◽  
Open Angle ◽  
Rho Kinase Inhibitor

Protective effect of hydroxyfasudil, a Rho kinase inhibitor, on ventral prostatic hyperplasia in the spontaneously hypertensive rat

The Prostate ◽  
2015 ◽  
Vol 75 (15) ◽  
pp. 1774-1782 ◽  
Author(s):  
Felix Holmström ◽  
Shogo Shimizu ◽  
Takahiro Shimizu ◽  
Youichirou Higashi ◽  
Darryl T. Martin ◽  
...  
Keyword(s):  
Protective Effect ◽  
Kinase Inhibitor ◽  
Spontaneously Hypertensive Rat ◽  
Rho Kinase ◽  
Prostatic Hyperplasia ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat ◽  
Rho Kinase Inhibitor
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