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Garcinia indica (Kokum) and Ilex aquifolium (European Holly)
Published in Azamal Husen, Herbs, Shrubs, and Trees of Potential Medicinal Benefits, 2022
Dicson Sheeja Malar, Mani Iyer Prasanth, Tewin Tencomnao, James Michael Brimson, Anchalee Prasansuklab
In prostate and gastric cancer cells, UA inhibits the mitochondrial translocation of cofilin-1 by targeting ROCK/PTEN signaling pathway leading to apoptosis (Gai et al. 2016; Mu et al., 2018; Li et al., 2014; Tang et al., 2014). UA shows apoptotic effect in prostate cancer cells through the inhibition of Wnt/β-catenin signaling (Park et al., 2013), PI3K/Akt/mTOR (Meng et al., 2015), while augmenting JNK pathway (Zhang et al., 2010a). Activation of JNK could induce the phosphorylation of Bcl-2 leading to its degradation, thereby reverting the resistance of cancer cells to apoptosis (Zhang et al., 2009; Zhang et al., 2010b). Invasion and metastasis of prostate cancer cells were found to be inhibited by UA through the modulation of pro-inflammatory pathways and inhibition of CXCR4/CXCL12 signaling axis in mouse models (Shanmugam et al., 2011; Shanmugam et al., 2012).
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).
Red Blood Cell and Platelet Mechanics
Published in Michel R. Labrosse, Cardiovascular Mechanics, 2018
The platelet cytoskeleton consists of three major components: a spectrin-based skeleton adherent to the plasma membrane, microtubule coils (marginal band) along the perimeter, and the cytoplasmic actin network. Actin is the most abundant protein, with 2 × 106 molecules per platelet. Approximately 800,000 actin monomers assemble to form 2000–4000 actin filaments (Hartwig and DeSisto 1991). The crosslinker protein filamin A was shown to be important for controlling the distribution of the GPIb-V-IX receptor on the platelet surface and attaching it to the actin cytoskeleton (Nakamura et al. 2006). On activation, platelets rearrange their cytoskeleton with the help of cytoskeletal-regulatory proteins (such as gelsolin, cofilin, profilin, Arp2/3, Wiskott–Aldrich Syndrome protein (WASP), and CapZ), change their discoid form to spherical shape, and tether the integrin αIIbβ3 to the underlying, newly assembled actin filaments. Finally, cytoplasmic myosin binds to actin polymers and applies contractile forces (Cove and Crawford 1975). In general, the platelet has turned out be a good model to study mechanobiological questions, since platelets are anucleated cells, have a high actin content, and highly express mechanical-relevant receptors, such as integrins (αIIbβ3: 80,000 copies), on a small surface (Ciciliano et al. 2014).
The roles of epidermal growth factor receptor in viral infections
Published in Growth Factors, 2022
Herpes simplex virus 1 (HSV-1) is another member of family Herpesviridae which is composed of a double-stranded linear DNA genome, an icosahedral nucleocapsid and an outer envelope with glycoprotein spikes. The infectious cycle of HSV-1 begins with a primary orolabial infection, establishment of latency in neurons and reactivation under specific conditions. Reactivation of HSV-1 causes cutaneous herpes, conjunctivitis, keratitis, encephalitis, or eczema herpeticum (Kukhanova, Korovina, and Kochetkov 2014; Kumar et al. 2016). Zheng et al. (2014) have reported that entry of HSV-1 into neuroblastoma (SK-N-SH) cell requires a cofilin-mediated biphasic remodelling of actin cytoskeleton. Similar to TGEV, EGFR signalling pathway is essential for the cofilin activity. In the early entry stage, HSV-1 induces phosphorylation of cofilin and F-actin polymerisation which facilitates virus entry via EGFR and its downstream PI3K/ERK1/2/ROCK/LIMK signalling pathways. Subsequently, cofilin is activated and promotes F-actin depolymerisation which allows viral penetration and intracellular trafficking. Treatments of EGFR inhibitor, AG1478 and siRNA inhibit phosphorylation of cofilin and disrupt HSV-1 entry (Figure 3(b)) (Zheng et al. 2014).
LIM kinase inhibitor T56-LIMKi protects mouse brain from photothrombotic stroke
Published in Brain Injury, 2021
Svetlana V. Demyanenko, Anatoly Uzdensky
T56-LIMKi that can penetrate into brain tissue was first developed as a drug for the treatment of neurofibromatosis in humans (26,44). Since T56-LIMKi prevents the LIMK-mediated cofilin inactivation and maintains its active state (26,27), one can suggest that its neuroprotective activity observed in the present work was associated with its participation in various brain regeneration processes. The observed protective effect of cofilin might be also associated with another mechanism. T56-LIMKi can prevent LIMK-induced microtubule disruption and thus stabilize the microtubular cytoskeleton, independently on the regulation of the actin filaments (27). This effect was observed in cancer cells but was not demonstrated yet in neurons, in which numerous microtubules provide mechanical firmness and stability of the axon and dendrites as well as transport of proteins, mRNA and mitochondria to remote neurite regions and synapses. It would be of interest to study the effect of T56-LIMKi on the neuronal structure after ischemic stroke to get clearer explanation of its neuroprotective capability.
Biochemical and immunocytochemical characterization of coronins in platelets
Published in Platelets, 2020
David R. J. Riley, Jawad S. Khalil, Khalid M. Naseem, Francisco Rivero
At high speed nearly all the Coro1 was recovered in the Triton X-100 insoluble pellet, which contains short actin filaments, even upon treatment with LatB, indicating that the association of Coro1 to the HS pellet is independent of an association with short actin filaments. We investigated the behavior of profilin and cofilin, two proteins involved in actin filament turnover. Profilin was recovered in the supernatants at both LS and HS, consistent with its role as monomeric actin-binding protein. Cofilin, which interacts with F-actin in addition to G-actin, was observed in HS and LS pellets and was removed from the LS pellet upon actin depolymerization, but not completely from the HS pellet. Coro1, as well as part of cofilin, may be associated with membranes or membrane proteins independently of actin, as suggested by the presence of a fraction of the membrane protein and lipid rafts component CD36 [22]. Syk was used as Triton X-100 soluble fraction marker to confirm that isolation of cytoskeleton fraction was clean.