Last update 01 Nov 2024

ROCK2 x ROCK1 x Akt

Last update 01 Nov 2024

Basic Info

Related Targets

ROCK2ROCK1Akt

Drugs associated with ROCK2 x ROCK1 x Akt

B-12(Zhejiang University)

Target

Akt x ROCK1 x ROCK2

Mechanism

Akt inhibitors [+2]

Active Org.

Zhejiang University

Originator Org.

Zhejiang University

Active Indication

Neuroblastoma

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with ROCK2 x ROCK1 x Akt

100 Translational Medicine associated with ROCK2 x ROCK1 x Akt

0 Patents (Medical) associated with ROCK2 x ROCK1 x Akt

Literatures (Medical) associated with ROCK2 x ROCK1 x Akt

01 Oct 2024·Molecular Neurobiology

M2 Microglia-Derived Exosomes Protect Against Glutamate-Induced HT22 Cell Injury via Exosomal miR-124-3p

Article

Author: Zheng, Hengheng ; Zhu, Lan ; Du, Xin ; Jiang, Yuhao ; Ma, Limei ; Zhang, Gaofeng ; Gao, Jiake ; Zhu, Jianjun ; Fan, Zihao

AbstractAs one of the most serious complications of sepsis, sepsis-associated encephalopathy has not been effectively treated or prevented. Exosomes, as a new therapeutic method, play a protective role in neurodegenerative diseases, stroke and traumatic brain injury in recent years. The purpose of this study was to investigate the role of exosomes in glutamate (Glu)-induced neuronal injury, and to explore its mechanism, providing new ideas for the treatment of sepsis-associated encephalopathy. The neuron damage model induced by Glu was established, and its metabolomics was analyzed and identified. BV2 cells were induced to differentiate into M1 and M2 subtypes. After the exosomes from both M1-BV2 cells and M2-BV2 cells were collected, exosome morphological identification was performed by transmission electron microscopy and exosome-specific markers were also detected. These exosomes were then cocultured with HT22 cells. CCK-8 method and LDH kit were used to detect cell viability and toxicity. Cell apoptosis, mitochondrial membrane potential and ROS content were respectively detected by flow cytometry, JC-1 assay and DCFH-DA assay. MiR-124-3p expression level was detected by qRT-PCR and Western blot. Bioinformatics analysis and luciferase reporter assay predicted and verified the relationship between miR-124-3p and ROCK1 or ROCK2. Through metabolomics, 81 different metabolites were found, including fructose, GABA, 2, 4-diaminobutyric acid, etc. The enrichment analysis of differential metabolites showed that they were mainly enriched in glutathione metabolism, glycine and serine metabolism, and urea cycle. M2 microglia-derived exosomes could reduce the apoptosis, decrease the accumulation of ROS, restore the mitochondrial membrane potential and the anti-oxidative stress ability in HT22 cells induced by Glu. It was also found that the protective effect of miR-124-3p mimic on neurons was comparable to that of M2-EXOs. Additionally, M2-EXOs might carry miR-124-3p to target ROCK1 and ROCK2 in neurons, affecting ROCK/PTEN/AKT/mTOR signaling pathway, and then reducing Glu-induced neuronal apoptosis. M2 microglia-derived exosomes may protect HT22 cells against Glu-induced injury by transferring miR-124-3p into HT22 cells, with ROCK being a target gene for miR-124-3p.

01 Aug 2022·Cellular Reprogramming

Signaling Pathways and Protein–Protein Interaction of Vimentin in Invasive and Migration Cells: A Review

Review

Author: Amirian, Mahdi ; Karoii, Danial Hashemi ; Azizi, Hossein

The vimentin (encoded by VIM) is one of the 70 human intermediate filaments (IFs), building highly dynamic and cell-type-specific web networks in the cytoplasm. Vim^-/- mice exhibit process defects associated with cell differentiation, which can have implications for understanding cancer and disease. This review showed recent reports from studies that unveiled vimentin intermediate filaments (VIFs) as an essential component of the cytoskeleton, followed by a description of vimentin's physiological functions and process reports in VIF signaling pathway and gene network studies. The main focus of the discussion is on vital signaling pathways associated with how VIF coordinates invasion cells and migration. The current research will open up multiple processes to research the function of VIF and other IF proteins in cellular and molecular biology, and they will lead to essential insights into different VIF levels for the invasive metastatic cancer cells. Enrich GO databases used Gene Ontology and Pathway Enrichment Analysis. Estimation with STRING online was to predict the functional and molecular interactions of proteins-protein with Cytoscape analysis to search and select the master genes. Using Cytoscape and STRING analysis, we presented eight genes, RhoA, Smad3, Akt1, Cdk2, Rock1, Rock2, Mapk1, and Mapk8, as the essential protein-protein interaction with vimentin involved in the invasion.

01 May 2022·Biochemical and Biophysical Research CommunicationsQ3 · BIOLOGY

Vascular smooth muscle ROCK1 contributes to hypoxia-induced pulmonary hypertension development in mice

Q3 · BIOLOGY

Article

Author: Kim, Young-Bum ; Penumatsa, Krishna C ; Qi, Guanming ; Fanburg, Barry L ; Bear, Michael D ; Bhedi, Chinmayee D ; Singhal, Adit A ; Hill, Nicholas S ; Warburton, Rod R ; Nasirova, Sabina ; Wilson, Jamie L ; Preston, Ioana R ; Toksoz, Deniz

Rho kinase (ROCK) is implicated in the development of pulmonary arterial hypertension (PAH) in which abnormal pulmonary vascular smooth muscle (VSM) contractility and remodeling lead to right heart failure. Pharmacologic ROCK inhibitors block experimental pulmonary hypertension (PH) development in rodents but can have off-target effects and do not distinguish between the two ROCK forms, ROCK1 and ROCK2, encoded by separate genes. An earlier study using gene knock out (KO) in mice indicated that VSM ROCK2 is required for experimental PH development, but the role of ROCK1 is not well understood. Here we investigated the in vivo role of ROCK1 in PH development by generating a VSM-targeted homozygous ROCK1 gene KO mouse strain. Adult control mice exposed to Sugen5416 (Su)/hypoxia treatment to induce PH had significantly increased right ventricular systolic pressures (RVSP) and RV hypertrophy versus normoxic controls. In contrast, Su/hypoxia-exposed VSM ROCK1 KO mice did not exhibit significant RVSP elevation, and RV hypertrophy was blunted. Su/hypoxia-induced pulmonary small vessel muscularization was similarly elevated in both control and VSM ROCK1 KO animals. siRNA-mediated ROCK1 knock-down (KD) in human PAH pulmonary arterial SM cells (PASMC) did not affect cell growth. However, ROCK1 KD led to reduced AKT and MYPT1 signaling in serotonin-treated PAH PASMC. The findings suggest that like VSM ROCK2, VSM ROCK1 actively contributes to PH development, but in distinction acts via nonproliferative pathways to promote hypoxemia, and thus may be a distinct therapeutic target in PH.

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