Disease relevance of ROCK1

• Ribozymes identified in this study, including the ribozymes against ROCK1, might be useful in understanding the mechanisms of cell migration and metastasis [1].
• The two ribozymes that specifically cleaved ROCK1 mRNA inhibited both the migration and invasion of invasive HT1080 fibrosarcoma, but neither had any effect on cell proliferation [1].
• In addition, overexpression of NF-kappaB p50 induced RhoA activity and Rock-mediated formation of stress fiber in melanoma cells [2].
• These data suggest an obligatory role for ROCK-1 cleavage in promoting apoptotic signals in myocardial hypertrophy and/or failure [3].
• CONCLUSION: These results suggest that ROCK-1 may contribute to pancreatic cancer cell invasion and/or metastasis by facilitating cancer cell migration [4].

Psychiatry related information on ROCK1

• Administration of Y-27632, a selective Rock inhibitor, also preferentially lowered brain levels of Abeta42 in a transgenic mouse model of Alzheimer's disease [5].
• The pharmacy curriculum which has been developed at the family practice residency program in Little Rock, Ark. focuses on problem-solving activities in the clinical setting, primarily utilizing problems from the residents' patient caseloads [6].

High impact information on ROCK1

• Y-27632, an inhibitor of the Rho-associated kinase p160ROCK, diminished polyglutamine protein aggregation (EC(50) congruent with 5 microM) and reduced neurodegeneration in a Drosophila model of polyglutamine disease [7].
• We demonstrate that macrophage adherence promotes rapid changes in physiological functions that depend on translational upregulation of preformed ROCK-1 mRNA, but not ROCK-2 mRNA [8].
• Inhibition of mTOR by rapamycin abolished ROCK-1 synthesis in macrophages resulting in an inhibition of chemotaxis and phagocytosis [8].
• In addition, there was a rapamycin/sirolimus-sensitive enhanced loading of ribosomes on preformed ROCK-1 mRNAs [8].
• Phosphoinositides and the Rho/p160 ROCK pathway, which participate in the activation of ERM proteins, were involved in the generation and maintenance of the anchoring structure [9].

Chemical compound and disease context of ROCK1

• To investigate whether the specific p160ROCK inhibitor, Y-27632, could also inhibit intrahepatic metastasis, the effect of Y-27632 on the cell motility and intrahepatic metastasis of Li7 was investigated [10].
• Medical records from all participants in the 1998 Suzuki Rock 'N' Roll Marathon who presented to 14 Emergency Departments (EDs) were retrospectively reviewed to identify risk factors for the development of hyponatremia [11].

Biological context of ROCK1

• However, the possibility that these enzymes play a role in statin-stimulated shedding has been excluded, leading us to investigate whether the Rho/ROCK1 protein phosphorylation pathway might be involved [12].
• In addition, phosphorylation of myosin light chain was further increased by TSA in suspension and higher in anchorage-independent cells over adherently growing cells, indicating an inverse relationship between ROCK1 expression-mediated contractility and cell adhesion abilities [13].
• Meanwhile, chromatin immunoprecipitation showed higher basal and TSA-enhanced associations of ROCK1 promoter regions with Lys(9)-acetylated histone 3 in suspended cells than in fibronectin-adherent cells and expression of ROCK1 was higher and further increased by TSA treatment in suspension [13].
• ROCK1 flanks USP14 in the long arm of the chimpanzee chromosome 17, which is homologous to human chromosome 18 [14].
• Using immunofluorescence with a variety of p160ROCK antibodies, immuno EM, and depletion with RNA interference, p160ROCK is principally bound to the mother centriole (MC) and an intercentriolar linker [15].

Anatomical context of ROCK1

• Here we show that endogenous SOX9 mRNA can be rapidly up-regulated in subcultured human articular chondrocytes if grown in alginate, in monolayer with cytochalasin D, or with specific inhibition of the RhoA effector kinases ROCK1 and -2, which all prevent actin stress fiber formation [16].
• CONCLUSION: Together, these data suggest that statins exert their effects on shedding of sAPP(alpha) from cultured cells, at least in part, by modulation of the isoprenoid pathway and ROCK1 [12].
• Taken together, our results demonstrate that the expression and activity of ROCK1 and ROCK2 can be uncoupled in a signal-dependent manner, and further implicate a new function for ROCK2 in the steroid control of tight junction dynamics [17].
• Thus, p160ROCK is required for centrosome positioning and centrosome-dependent exit from mitosis [15].
• Similarly, ROCK-1-null mice (Rock-1(-/-)) showed a marked reduction in myocyte apoptosis associated with pressure overload [3].

Associations of ROCK1 with chemical compounds

• We also demonstrate that p160ROCK, a serine/threonine kinase effector of RhoA, is both necessary and sufficient for RhoA-mediated tail retraction [18].
• Murine cardiomyocytes treated with doxorubicin led to enhanced ROCK-1 cleavage and apoptosis, all of which was blocked by a caspase-3 inhibitor [3].
• Elevation of [Ca(2+)](cyt) induced by the Ca(2+) ionophore ionomycin increased GTP-bound RhoA, ROCK-1, and ROKalpha proteins, Rho-kinase activity, and MLC phosphorylation [19].
• Y-27632, a selective inhibitor of p160ROCK, impeded the cellular redistribution of lysosomes and promoted reclustering of lysosomes toward the perinuclear region [20].
• They include lipid kinases such as phosphatidyl-inositol-5-kinase and protein serine/threonine kinases such as PKN and p160ROCK [21].

Physical interactions of ROCK1

• Its association with caveolin-1 was evidenced by the demonstration that the 160kDa proenzyme form of Rock-1 co-immunoprecipitates with caveolin-1 and vice versa, as well as by the co-localisation of the two proteins at the plasma membrane, as shown in immunofluorescence studies [22].

Regulatory relationships of ROCK1

• Most conclusively, a constitutively active ROCK1 molecule inhibited statin-stimulated sAPP(alpha) shedding [12].
• We conclude that cell-cell contact is required for BeWo trophoblast to exhibit plasmalemmal caveolin-1; BeWo cells at confluence offer a useful model for the study of trophoblast raft behaviour during syncytialisation and for the exploration of the potential Rock-1-regulating role of caveolin-1 in this process [22].

Other interactions of ROCK1

• That this is of importance is supported by the findings that an increased Rho-kinase/ROCK activity in SW13 cells, obtained by overexpressing wild-type ROCK1 and ROCK2, induces stress-fibre formation [23].
• Our results suggest that the BRG1 protein affects the RhoA pathway by increasing the protein level of ROCK1, which allows stress-fibre-like structures to form [23].
• In this chapter, we will discuss the role of these Rho family GTPases and their effectors, in particular the Ser/Thr kinases PAK1 and Rock, in RAS-induced serum/anchorage-independent cell cycling, and discuss several potential therapeutics, peptides or chemical compounds, that could block this oncogenic cell cycle signalling pathway [24].
• It includes the MAP kinase cascade, the Ca/calmodulin system, several heterotrimeric G proteins (Galpha12, Galpha13, Galphaq, and Galphai), small G proteins (ras, cdc42, rhoA), and downstream kinases (e.g., p160ROCK) [25].
• Y-27632, a specific inhibitor of ROCK-1, blocked LDL-induced stress fiber formation, eNOS translocation and NO production [26].

Analytical, diagnostic and therapeutic context of ROCK1

• However, with the recent development of ROCK1- and ROCK2-knockout mice, further dissection of ROCK signaling pathways is now possible [27].
• RESULTS: The expression of ROCK-1 was found in 18 of 21 PC tissues (85.7%), but not in normal pancreatic tissues by immunoblotting and immunohistochemistry [4].
• Western blot analysis revealed the expression of ROCK-1 and ROCK-II isoforms in aorta segments from both groups [28].
• In total, the highest number of errors occurred at the North Little Rock Ambulatory Care Pharmacy (39 errors) and the Little Rock Ambulatory Care Pharmacy (24 errors) [29].
• Age-adjusted seroprevalence rates at titers of at least 64 varied from 21.9% in Little Rock, Ark, to 3.5% in Louisville, Ky [30].

References