• The Korean Journal of Mycology
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• v.46 no.2
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• pp.161-176
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• 2018

Fungal ${\beta}$-glucan, known to have immunostimulatory and antitumor activities, can be recognized by host immune cells as one of the pathogen-associated molecular patterns (PAMPs). Although there are several reports on the diverse immunostimulatory activities of ${\beta}$-glucan, little is known about the intracellular signal transduction of ${\beta}$-glucan. Stimulation of RAW264.7 macrophage cells with ${\beta}$-glucan from Ganoderma lucidum induced the expressions of dectin-1, toll-like receptor 2 (TLR2), TLR4, and TLR6 at the transcription stage. Treatment with ${\beta}$-glucan also induced inflammatory mediators such as macrophage inflammatory proteins (MIP)-$1{\alpha}$, MIP-$1{\beta}$, MIP-$1{\gamma}$, interleukin (IL)-$1{\beta}$, and tumor necrosis factor (TNF)-${\alpha}$. Treatment of the cells with polymyxin B, an inhibitor of lipopolysaccharides (LPS), blocked the induction of inflammatory mediators in LPS- or ${\beta}$-glucan-stimulated systems. Pretreatment of the cells in our cell culture system with LY294002, a phosphoinositide 3-kinase (PI3K) inhibitor, or U0126, a mitogen-activated protein kinase/extracellular-signal-regulated kinase (MAPK/ERK) kinase (MEK)1/MEK2 inhibitor, led to a reduction in the induction of inflammatory mediators in a concentration-dependent manner. These results show that stimulation of the macrophage cells by ${\beta}$-glucan induced the expressions of both dectin-1 and TLRs. We also found that the PI3K/Akt and MEK pathways were involved in the induction of inflammatory mediators in macrophage cells during intracellular signal transduction of ${\beta}$-glucan.

• Korean Journal of Biological Psychiatry
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• v.18 no.4
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• pp.189-196
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• 2011

Major depressive disorder is characterized by cellular and molecular alterations resulting in the depressive behavioral phenotypes. Preclinical and clinical studies have demonstrated the deficits, including cell atrophy and loss, in limbic and cortical regions of patients with depression, which is restored with antidepressants by reestablishing proper molecular changes. These findings have implicated the involvement of relevant intracellular signaling pathways in the pathogenetic and therapeutic mechanisms of depressive disorders. This review summarizes the current knowledge of the signal transduction mechanisms related to depressive disorders, including cyclic-AMP, mitogen-activated protein kinase, Akt, and protein translation initiation signaling cascades. Understanding molecular components of signaling pathways regulating neurobiology of depressive disorders may provide the novel targets for the development of more efficacious treatment modalities.

• The Journal of Korean Physical Therapy
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• v.19 no.4
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• pp.1-14
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• 2007

Background: It is generally accepted that skeletal muscle contraction is triggered by nerve impulse and intracellular $Ca^{2+}\;([Ca^{2+}]_i)$ released from intracellular $Ca^{2+}$ stores such as sarcoplasmic reticulum (SR). Specifically, this process, called excitation-contraction (E-C) coupling, takes place at intracellular junctions between the plasma membrane, the transverse (T) tubule L-type $Ca^{2+}$ channel (dihydropyridine-sensitive L-rype $Ca^{2+}$ channel, DHPR, also called tetrads), and the SR $Ca^{2+}$ release channel (ryanodine-sensitive $Ca^{2+}$ release channel, RyR, also called feet) of internal $Ca^{2+}$ stores in skeletal muscle cells. Furthermore, it has been reported that the $Ca^{2+-}$ dependent and -independent contraction determine the expression of skeletal muscle genes, thus providing a mechanism for tightly coupling the extent of muscle contraction to regulation of muscle plasticity-related excitation-transcription (E-T) coupling. Purpose: Expression and activity of plasticity-associated enzymes in gastrocnemius muscle strips have not been well studied, however. Methods: Therefore, in this study the expression and phosphorylation of E-C and E-T coupling-related mediators such as protein kinases, ROS(reactive oxygen species)- and apoptosis-related substances, and others in gastrocnemius muscles from rats was examined. Results: I found that expression and activity of MAPKs (mitogen-activated protein kinases, ERK1/2, p38MAPK, and SAPK/JNK), apoptotic proteins (cleaved caspase-3, cytochrome c, Ref-1, Bad), small GTP-binding proteins (RhoA and Cdc42), actin-binding protein (cofilin), PKC (protein kinase C) and $Ca^{2+}$ channel (transient receptor potential channel 6, TRPC6) was observed in rat gastrocnemius muscle strips. Conclusion: These results suggest that MAPKs, ROS- and apoptosis-related enzymes, cytoskeleton-regulated proteins, and $Ca^{2+}$ channel may in part functionally import in E-C and E-T coupling from rat skeletal muscles.

• Toxicological Research
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• v.22 no.1
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• pp.23-30
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• 2006

Among poly aromatic hydrocarbons, dioxin and PCBs are the most controversial environmental pollutants in our modern life. These pollutants are known as human carcinogens, and liver is the most sensitive target in animal cancer models. Specific aims of the study were focused on the mechanism of carcinogenesis in hepatocytes and the structure-activity relation among these diverse environmental chemicals. Because key mechanisms of dioxin-induced carcinogenesis in human epithelial cell model are the alteration of signal transduction pathway and PKC isoforms, the alteration of the signal transduction pathways and other factors associated with carcinogenesis were studied. Rat hepatocytes cultured under the sandwich protocols were exposed with the various concentration of dioxins and PCBs, and signal transduction pathway, protein kinase C isoforms, oxidant stress, and apoptotic nuclei were evaluated. Since it is important to understand the structure-activity relation among these chemicals to properly assess the carcinogenic potentials, the study analyzed the parameters associated with carcinogenic processes, based on their structural characteristics. In addition, signal transduction pathways and PKC isoforms involved in inhibition of UV-induced apoptosis were also analyzed to elaborate the tumor promotion mechanism of these chemicals. Induction of apoptosis by UV irradiation was optimal at $60\;J/m^2$ in primary hepatocyte in culture. Compared to non coplanar PCBs such as PCB 114 and PCB 153, coplanar PCBs such as PCB 77 and PCB126 showed a stronger inhibition of apoptosis induced by UV irradiation. Production of reactive oxygen species (ROS) was more stimulated by non-coplanar PCBs than coplanar PCBs with the most potent induction of ROS by chlorinated non-coplanar PCB. As compared to the level of induction by PCB126, non-coplanar PCB153 showed a higher increase of intracellular concentrations. Besides the alteration of intracellular calcium concentration, translocation of PKC from cytosolic fraction to membrane fraction was clearly observed upon the exposure of non-coplanar PCB. Taken together, the present study demonstrated that there is a potent structure-activity relationship among PCB congeners and the mechanism of PAH-induced carcinogenesis is structure-specific. The study suggested that more diverse pathways of PAH-induced carcinogenesis should be taken into account beyond the boundary of Ah receptor dogma to assess the health impact of PAH with more accuracy.

• Archives of Pharmacal Research
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• v.28 no.4
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• pp.413-420
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• 2005

We previously demonstrated the ability of ginseng saponins (active ingredients of Panax ginseng) to enhance $Ca^{2+}$-activated $Cl^{-}$ current. The mechanism for this ginseng saponin-induced enhancement was proposed to be the release of $Ca^{2+}$ from $IP_{3}-sensitive$ intracellular stores through the activation of PTX-insensitive $G\alpha_{q/11}$ proteins and PLC pathway. Recent studies have shown that calmodulin (CaM) regulates $IP_{3}$ receptor-mediated $Ca^{2+}$ release in both $Ca^{2+}-dependent$ and -independent manner. In the present study, we have investigated the effects of CaM on ginseng saponin-induced $Ca^{2+}$-activated $Cl^{-}$ current responses in Xenopus oocytes. Intraoocyte injection of CaM inhibited ginseng saponin-induced $Ca^{2+}$-activated $Cl^{-}$ current enhancement, whereas co-injection of calmidazolium, a CaM antagonist, with CaM blocked CaM action. The inhibitory effect of CaM on ginseng saponin-induced $Ca^{2+}$-activated $Cl^{-}$ current enhancement was dose- and time-dependent, with an $IC_{50} of 14.9\pm3.5 {\mu}M$. The inhibitory effect of CaM on saponin's activity was maximal after 6 h of intraoocyte injection of CaM, and after 48 h the activity of saponin recovered to control level. The half-recovery time was calculated to be $16.7\pm4.3 h$. Intraoocyte injection of CaM inhibited $Ca^{2+}$-induced $Ca^{2+}$-activated $Cl^{-}$ current enhancement and also attenuated $IP_{3}$-induced $Ca^{2+}$-activated $Cl^{-}$ current enhancement. $Ca^{2+}$/CaM kinase II inhibitor did not inhibit CaM-caused attenuation of ginseng saponin-induced $Ca^{2+}$-activated $Cl^{-}$ current enhancement. These results suggest that CaM regulates ginseng saponin effect on $Ca^{2+}$-activated $Cl^{-}$ current enhancement via $Ca^{2+}$-independent manner.

• The Korean Journal of Food And Nutrition
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• v.29 no.3
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• pp.341-346
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• 2016

Phagocytosis is a primary and an essential step of host defense, and is triggered by the interaction of particles with specific receptor of macrophages. In this study, we investigated the effect of extracts of Rudbeckia laciniata (RLE) on the phagocytic activity of macrophage, by monitoring the phagocytosis-associated signal transduction. RLE markedly increased phagocytosis of serum-opsonized zymosan particles (SOZ), while phagocytosis of IgG-opsonized zymosan particles (IOZ) or none-opsonized zymosan particles (NOZ) remained unaffected. However, RLE did not affect the binding of opsonized zymosan particles (OZ) with the cell surface of macrophage. This suggests that RLE may regulate SOZ-induced intracellular signaling during phagocytosis of macrophage. To confirm this hypothesis, we investigated whether RLE was involved in the RhoA-mediated signal transduction during phagocytosis of SOZ. Inhibitors of the RhoA-mediated signaling pathway, such as Y-27632 (for ROCK), ML-7 (for MLCK), and Tat-C3 (for RhoA), totally blocked phagocytosis of SOZ enhanced by RLE, as well as phagocytosis of SOZ. Additionally, RhoA activity was markedly increased when cells were treated with RLE, suggesting that RLE could increase the phagocytic activity of macrophage via RhoA-ROCK/MLCK signal pathway. Thus, RLE may be used to develop functional foods for immunity.

• Proceedings of the Korean Biophysical Society Conference
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• 1997.07a
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• pp.15-15
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• 1997

Recent studies indicate that hydrogen peroxide (H$_2$O$_2$), which is one of the reactive oxygen species involved in the oxidative stress, is an intracellular secondary messenger in the signal transduction. A novel family of thiol specific antioxidant (TSA) enzymes with a peroxidase activity shows no sequence homology to previously known antioxidant enzymes.(omitted)

• Biomolecules & Therapeutics
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• v.27 no.4
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• pp.337-341
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• 2019

Primary cilia and autophagy are two distinct nutrient-sensing machineries required for maintaining intracellular energy homeostasis, either via signal transduction or recycling of macromolecules from cargo breakdown, respectively. Potential correlations between primary cilia and autophagy have been recently suggested and their relationship may increase our understanding of the pathogenesis of human diseases, including ciliopathies and cancer. In this review, we cover the current issues concerning the bidirectional interaction between primary cilia and autophagy and discuss its role in cancer with cilia defect.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.207.2-207.2
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• 2003

cAMP acts as a second messenger in the functional responses of various cells to hormones, cytokines and other agents. In turn, this nucleotide also modulates the signal transduction processes regulated by a range of cytokines and growth factors. The intracellular level of cAMP is regulated by a G protein coupled adenylyl cyclase and degradation is mediated by the phosphodiesterases (PDEs), a superfamily of enzymes that catalyze the hydrolysis of cAMP. (omitted)

• Development and Reproduction
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• v.19 no.2
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• pp.61-67
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• 2015

The immediate early gene c-fos has long been known as a molecular marker of neural activity. The neuron's activity is transformed into intracellular calcium influx through NMDA receptors and L-type voltage sensitive calcium channels. For the transcription of c-fos, neural activity should be strong enough to activate mitogen-activated protein kinase (MAPK) signaling pathway which shows low calcium sensitivity. Upon translation, the auto-inhibition by Fos protein regulates basal Fos expression. The pattern of external stimuli and the valence of the stimulus to the animal change Fos signal, thus the signal reflects learning and memory aspects. Understanding the features of multiple components regulating Fos signaling is necessary for the optimal generation and interpretation of Fos signal.