• BMB Reports
• /
• v.32 no.1
• /
• pp.28-32
• /
• 1999

Annexin I (also called lipocortin 1), a 37-kDa member of the annexin family of proteins, has been implicated in the mitogenic signal transduction by epidermal growth factor (EGF). Annexin I is phosphorylated by the EGF signal, however, the role of annexin I in the EGF signal transduction is still unknown. To transduce extracellular signals into the intracellular targets, selective translocation of the signaling molecules to their targets would be necessary. In this study, we examined the subcellular locations of annexin I during EGF signal transduction. Treatment of A549 cells with EGF resulted in the translocation of cytoplasmic annexin I to the nucleus and perinuclear region as determined by Western blot and immunofluorescent staining. The nuclear translocation of annexin I was inhibited by tyrphostin AG 1478 and genistein, the inhibitors of EGF receptor kinase and downstream tyrosine kineses, respectively. Pretreatment of cells with cyclohexamide did not inhibit the nuclear translocation. The results suggest that nuclear translocation of annexin I is controlled by a series of kinase dependent events in the EGF receptor signaling pathway and may be important in tranducing the signals by EGF.

• BMB Reports
• /
• v.44 no.12
• /
• pp.782-786
• /
• 2011

Aberrant GAPDH expression following S-nitrosoglutathione (GSNO) treatment was compared in HepG2 cells, which express functional p53, and Hep3B cells, which lack functional p53. The results of Western blotting and fluorescent immunocytochemistry revealed that nuclear translocation and accumulation of GAPDH occur in both HepG2 and Hep3B cells. This finding suggests that p53 may not be necessary for the GSNO-induced translocation of GAPDH to the nucleus during apoptotic cell death in hepatoma cells.

• Toxicological Research
• /
• v.21 no.4
• /
• pp.285-290
• /
• 2005

We demonstrate that radicicol, a macrocyclic antifungal antibiotic originally isolated from Monosporium bonorden, inhibits LPS-induced expression of iNOS gene in RAW 264.7 cells. Treatment of peritoneal macrophages and RAW 264.7 cells with radicicol inhibited LPS-stimulated nitric oxide production in a dose-related manner. Immunohistochemical staining of iNOS and RTPCR analysis showed that the decrease of NO was due to the inhibition of iNOS gene expression in RAW 264.7 cells. Immunostaining of p65, EMSA, and reporter gene assay showed that radicicol inhibited $NF-\kappa/Rel$ nuclear translocation. DNA binding, and transcriptional activation, respectively. Collectively, these series of experiments indicate that radicicol inhibits iNOS gene expression by blocking $NF-\kappa/Rel$ nuclear translocation. Due to the critical role that NO release plays in mediating inflammatory responses, the inhibitory effects of radicicol on iNOS suggest that radicicol may represent a useful anti-inflammatory agent.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 2001.11a
• /
• pp.101-101
• /
• 2001

In the present study, we explored to determine if insulin has any effect on the nuclear translocation of insulin receptor and tyrosine phosphoryaltion of nuclear proteins in the UMR-106 cells. Significant amount of insulin receptors and IRS-1 proteins were detected in the nucleus. IRS-1 and PI$_3$-Kinase appeared to translocate to the nucleus in a time dependent manner. Tyrosine phosphorylation of a number of proteins including 180 KDa, 85 KDa protein in the nucleus was significantly stimulated by insulin, suggesting IRS-1 and PI$_3$-Klnase was activated in the nucleus by insulin treatment. In addition, p70 S6 Kinase, a downstream target of PI3-Kinase was transiently appeared in the nucleus by insulin and its activity was stimulated by insulin. These results suggest that the insulin signaling system containing insulin receptor, IRS-1, PI$_3$-Kinase and p70 S6 Kinase operates in the nucleus of osteoblast cells. The nuclear insulin-mediated tyrosine phosphorylation may play an essential role in the gene expression, differentiation and growth of osteoblast cells.

• Proceedings of the PSK Conference
• /
• 2002.10a
• /
• pp.241.3-242
• /
• 2002

Expression of phase II detoxifying genes is regulated by NF-E2-related factor 2 (Nrf2)-mediated antioxidant response element (ARE) activation. Phosphatidylinositol 3-kinase (PI3-kinase) plays an essential role in ARE-mediated rGSTA2 induction by oxidative stress and controls microfilaments and translocation of actin-associated proteins. This study was designed to investigate the P13-kinase-mediated nuclear translocation of Nrf2 and the interaction of Nrf2 with actin. (omitted)

• Nuclear Engineering and Technology
• /
• v.8 no.3
• /
• pp.139-143
• /
• 1976

$^{32}$ P was supplied to the roots of stem-ringed 1-year-old apple trees and 2-year-old citrus trees on which bark segments were isolated above and below the ring. $^{32}$ P was translocated to shoots and leaves although considerable translocation occurred especially in wood and bark tissues. The accumulation of $^{32}$ P in isolated bark segments indicated that the occurrence of these materials in this tissue was via radial translocation from xylem tissue, and that the main upward translocation pathway of $^{32}$ P supplied to roots is through the xylem.

• Biomolecules & Therapeutics
• /
• v.24 no.3
• /
• pp.268-282
• /
• 2016

In the present study, we investigated the anti-inflammatory properties of Eucommia ulmoides Oliv. Bark. (EUE) in lipopolysaccharide (LPS)-stimulated microglial BV-2 cells and found that EUE inhibited LPS-mediated up-regulation of pro-inflammatory response factors. In addition, EUE inhibited the elevated production of pro-inflammatory cytokines, mediators, and reactive oxygen species (ROS) in LPS-stimulated BV-2 microglial cells. Subsequent mechanistic studies revealed that EUE suppressed LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs), phosphoinositide-3-kinase (PI3K)/Akt, glycogen synthase $kinase-3{\beta}$ ($GSK-3{\beta}$), and their downstream transcription factor, nuclear factor-kappa B ($NF-{\kappa}B$). EUE also blocked the nuclear translocation of $NF-{\kappa}B$ and inhibited its binding to DNA. We next demonstrated that EUE induced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulated heme oxygenase-1 (HO-1) expression. We determined that the significant up-regulation of HO-1 expression by EUE was a consequence of Nrf2 nuclear translocation; furthermore, EUE increased the DNA binding of Nrf2. In contrast, zinc protoporphyrin (ZnPP), a specific HO-1 inhibitor, blocked the ability of EUE to inhibit NO and $PGE_2$ production, indicating the vital role of HO-1. Overall, our results indicate that EUE inhibits pro-inflammatory responses by modulating MAPKs, PI3K/Akt, and $GSK-3{\beta}$, consequently suppressing $NF-{\kappa}B$ activation and inducing Nrf2-dependent HO-1 activation.

• Toxicological Research
• /
• v.27 no.2
• /
• pp.71-76
• /
• 2011

We demonstrate that baicalein, a bioactive flavonoid originally isolated from Scutellaria baicalensis, inhibits LPS-induced expression of iNOS gene in RAW 264.7 cells. Treatment of peritoneal macrophages and RAW 264.7 cells with baicalein inhibited LPS-stimulated nitric oxide production in a dose-related manner. Immunohistochemical staining of iNOS and RT-PCR analysis showed that the decrease of NO was due to the inhibition of iNOS gene expression in RAW 264.7 cells. Immunostaining of p65, EMSA, and reporter gene assay showed that baicalein inhibited NF-${\kappa}$B nuclear translocation, DNA binding, and transcriptional activation, respectively. Collectively, these series of experiments indicate that baicalein inhibits iNOS gene expression by blocking NF-${\kappa}$B nuclear translocation. Due to the critical role that NO release plays in mediating inflammatory responses, the inhibitory effects of baicalein on iNOS suggest that baicalein may represent a useful anti-inflammatory agent.

• 대한약리학회:학술대회논문집
• /
• 2006.11a
• /
• pp.61-61
• /
• 2006

• Molecules and Cells
• /
• v.22 no.2
• /
• pp.203-209
• /
• 2006

TBP (TATA-binding protein)-related factor 2 (TRF2) regulates transcription during a nuber of cellular processes. We previously demonstrated that it is localized in the cytoplasm and is translocated to the nucleus by DNA-damaging agents. However, the cytoplasmic localization of TRF2 is controversial. In this study, we reconfirmed its cytoplasmic localization in various ways and examined its nuclear migration. Stresses such as heat shock, redox agents, heavy metals, and osmotic shock did not affect localization whereas genotoxins such as methyl methanesulfonate (MMS), cisplatin, etoposide, and hydroxyurea caused it to migrate to the nucleus. Adriamycin, mitomycin C and ${\gamma}$-rays had no obvious effect. We determined optimal conditions for the nuclear migration. The proportions of cells with nuclei enriched for TRF2 were 25-60% and 5-10% for stressed cells and control cells, respectively. Nuclear translocation was observed after 1 h, 4 h and 12 h for cisplatin, etoposide and MMS and hydroxyurea, respectively. The association of TRF2 with the chromatin and promoter region of the proliferating cell nuclear antigen (PCNA) gene, a putative target of TRF2, was increased by MMS treatment. Thus TRF2 may be involved in genotoxin-induced transcriptional regulation.