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Cytotoxic Phenanthridone Alkaloid Constituents of the Amaryllidaceae
Published in Spyridon E. Kintzios, Maria G. Barberaki, Evangelia A. Flampouri, Plants That Fight Cancer, 2019
Jerald J. Nair, Johannes van Staden
On the other hand, narciclasine (11) impaired glioblastoma multiforme cell growth by markedly decreasing mitotic rates without inducing apoptosis (LeFranc et al. 2009). It also activated the Rho/Rho kinase/LIM kinase/cofilin signaling pathway by increasing GTPase RhoA activity as well as inducing actin stress fiber formation in a RhoA-dependent manner (LeFranc et al. 2009). Since glioblastoma cells are capable of migrating through the narrow extracellular spaces in brain tissue and traveling relatively long distances, these cancers are a significant challenge for effective surgical management (LeFranc et al. 2009). Consequently, sufferers have a median survival period of only 14 months following the current standard treatment of surgical resection and adjuvant radio- and chemotherapy (LeFranc et al. 2009). Given these dismal prognoses as well as the promising preclinical results acquired for narciclasine, the phenanthridones have been heralded as promising targets in therapeutic approaches towards brain cancer (Van Goietsenoven et al. 2013).
Structure and function of the mesothelial cell
Published in Wim P. Ceelen, Edward A. Levine, Intraperitoneal Cancer Therapy, 2015
Steven E. Mutsaers, Cecilia M. Prêle, Sarah E. Herrick
Mesothelial cells are also likely to play a role in cancer cell invasion. Mesothelial cells produce lysophosphatidic acid (LPA), which is a biologically active lipid able to stimulate adhesion, migration, and invasion of ovarian cancer cells [137,138]. LPA produced by cultured mesothelial cells induced ovarian cancer cell migration, cell adhesion to collagen type I, and cell invasion across a mesothelial monolayer, involving LPA1 and LPA2 receptors. LPA has also been shown to stimulate the proliferation and motility of mesothelioma cells through LPA1 and LPA2 receptors [139]. Furthermore, LPA stimulates VEGF production by mesothelial cells that may play a significant role in tumor angiogenesis [140]. Various studies have examined ways to block LPA-induced tumor cell proliferation, chemotaxis, and invasion. Ovarian cancer cells treated with secreted protein acidic and rich in cysteine inhibited LPA-induced mesothelial–ovarian cancer cell crosstalk through the regulation of both LPA-induced IL-6 production and function [141]. The knockdown of cofilin/ADF, LIM kinase-1 (LIMK1), or Slingshot (SSH)1/SSH2 expression by small interfering RNAs significantly decreased the LPA-induced transcellular migration of rat hepatoma cells and their motility in 2D culture. The knockdown of LIMK1 also suppressed fibronectin-mediated cell attachment and focal adhesion formation [142].
S1P in the development of atherosclerosis: roles of hemodynamic wall shear stress and endothelial permeability
Published in Tissue Barriers, 2021
Christina M Warboys, Peter D Weinberg
Exposure of endothelial cells to S1P results in rapid actin polymerization and dynamic reorganization of the actin cytoskeleton, forming a prominent cortical actin band29,33,36,37,41 that is essential for the barrier-enhancing effects of S1P.29 Several studies have also shown that Rac GTPase is rapidly activated in response to S1P29,38,39,41 and that this depends on the activation of PI3K and recruitment of Tiam1, a Rac1 guanine nucleotide exchange factor.37 Rac plays a critical role in mediating S1P-induced cytoskeletal remodeling via activation of p21-associated Ser/Thr kinase (PAK).29,41 PAK may act at several levels to promote the dynamic reorganization of the cytoskeleton into dense peripheral bands that strengthen barrier function. Myosin light chain (MLC) can be phosphorylated by PAK61 and indeed phosphorylated MLC has been shown to localize to peripheral bands in response to S1P.29,36 PAK also phosphorylates and activates LIM kinase (LIMK), which inhibits cofilin (an actin severing protein) thus preventing actin depolymerization and promoting the formation of actin filaments.62
Experience and activity-dependent control of glucocorticoid receptors during the stress response in large-scale brain networks
Published in Stress, 2021
Damien Huzard, Virginie Rappeneau, Onno C. Meijer, Chadi Touma, Margarita Arango-Lievano, Michael J. Garabedian, Freddy Jeanneteau
Mechanisms of adaptive plasticity utilize immediate early genes as first-line responders to glucocorticoid stimulation to prepare cells for a changing environment based on prior experience. For example, the MAPK specific phosphatases (Mitogen-Activated Protein Kinase Phosphatase 1/6 [MKP1/6]) are induced to terminate coincident growth factor signaling pathways converging on the GR phosphorylation code and the epigenome (Deinhardt & Jeanneteau, 2012; Jeanneteau & Deinhardt, 2011). Another example is the stress-induced transcription factors NR4A1/2/3, which shuttle in and out of the nucleus and mitochondria to coordinate metabolism and synapses number (Jeanneteau et al., 2018). Finally, actin binding proteins such as the Ca2+ sensor caldesmon and the cofilin kinase LIM-kinase 1 (LIMK1) are induced to reorganize the cytoskeleton supporting neuronal migration, differentiation, and connectivity (Fukumoto et al., 2009; Mayanagi et al., 2008; Morsink et al., 2006). Altogether, these responses set in motion the adaptive machinery that updates many attributes of neuronal function to its environment based on prior experience.
Migraine as an inflammatory disorder with microglial activation as a prime candidate
Published in Neurological Research, 2023
Amrit Sudershan, Mohd Younis, Srishty Sudershan, Parvinder Kumar
Upon activation, ROCK phosphorylated LIMK1 (LIM-kinase 1) on the threonine residue (Thr-508) which further on phosphorylates another protein that acts as an actin-depolymerizing factor known as cofilin [97]. Cofilin is a powerful regulator of actin filament dynamics, and phosphorylation of serine residue 3 eliminates its ability to bind and depolymerize actin filaments [98]. The constant restructuring of the cytoskeleton, especially actin filament, provides the network for intracellular protein transport and notably nociceptive signals [99]. RhoA/ROCK has been identified as having a vital involvement in p38 MAPK activation and plays a key impact on pain hypersensitive modulation [100] (Figure 2d).