• Journal of Ginseng Research
• /
• v.44 no.4
• /
• pp.593-602
• /
• 2020

Background: Heat stress orchestrates neurodegenerative disorders and results in the formation of reactive oxygen species that leads to cell death. Although the immunomodulatory effects of ginseng are well studied, the mechanism by which ginseng alleviates heat stress in the brain remains elusive. Methods: Rats were exposed to intermittent heat stress for 6 months, and brain samples were examined to elucidate survival and antiinflammatory effect after Korean Red Ginseng (KRG) treatment. Results: Intermittent long-term heat stress (ILTHS) upregulated the expression of cyclooxygenase 2 and inducible nitric oxide synthase, increasing infiltration of inflammatory cells (hematoxylin and eosin staining) and the level of proinflammatory cytokines [tumor necrosis factor α, interferon gamma (IFN-γ), interleukin (IL)-1β, IL-6], leading to cell death (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay) and elevated markers of oxidative stress damage (myeloperoxidase and malondialdehyde), resulting in the downregulation of antiapoptotic markers (Bcl-2 and Bcl-x_L) and expression of estrogen receptor beta and brain-derived neurotrophic factor, key factors in regulating neuronal cell survival. In contrast, KRG mitigated ILTHS-induced release of proinflammatory mediators, upregulated the mRNA level of the antiinflammatory cytokine IL-10, and increased myeloperoxidase and malondialdehyde levels. In addition, KRG significantly decreased the expression of the proapoptotic marker (Bax), did not affect caspase-3 expression, but increased the expression of antiapoptotic markers (Bcl-2 and Bcl-x_L). Furthermore, KRG significantly activated the expression of both estrogen receptor beta and brain-derived neurotrophic factor. Conclusion: ILTHS induced oxidative stress responses and inflammatory molecules, which can lead to impaired neurogenesis and ultimately neuronal death, whereas, KRG, being the antioxidant, inhibited neuronal damage and increased cell viability.

• Journal of Life Science
• /
• v.17 no.1 s.81
• /
• pp.150-161
• /
• 2007

Acori graminei Rhizomn (AGR) is a perennial herb which has been used clinically as a traditional oriental medicine against stroke, Alzheimer's disease, and vascular dementia. We investigated the effect of AGR on the modulation of gene expression profile in a hypoxic model of cultured rat cortical cells. Rat cerebrocortical cells were grown in Neurobasal medium. On DIV12, cells were treated with AGR $(10ug/m\ell)$, given a hypoxic shock (2% $O_2$, 3 hr) on DIV14, and total RNAs were prepared one day after shock. Microarray analyses indicated that the expression levels of most genes were altered within the global M values +0.5 and -0.5, i.e., 40% increase or decrease. There were 750 genes which were upregulated by < global M +0,2, while 700 genes were downregulated by > global M -0.2. The overall profile of gene expression suggests that AGR suppresses apoptosis (upregulation of anti-apopotic genes such as TEGT, TIEG, Dad, p53, and downregulation of pro-apopotic genes such as DAPK, caspase 2, pdcd8), ROS (upregulation of RARa, AhR), and that AGR has neurotrophic effects (upregulation of Aktl, Akt2). These results provide a platform for investigation of the molecular mechanism of the effect of AGR in neuroprotection.

• Molecules and Cells
• /
• v.39 no.3
• /
• pp.266-279
• /
• 2016

The mechanism by which 12-O-tetradecanoylphorbol-13-acetate (TPA) bypasses cellular senescence was investigated using human diploid fibroblast (HDF) cell replicative senescence as a model. Upon TPA treatment, protein kinase C (PKC) ${\alpha}$ and $PKC{\beta}1$ exerted differential effects on the nuclear translocation of cytoplasmic pErk1/2, a protein which maintains senescence. $PKC{\alpha}$ accompanied pErk1/2 to the nucleus after freeing it from $PEA-15pS^{104}$ via $PKC{\beta}1$ and then was rapidly ubiquitinated and degraded within the nucleus. Mitogen-activated protein kinase docking motif and kinase activity of $PKC{\alpha}$ were both required for pErk1/2 transport to the nucleus. Repetitive exposure of mouse skin to TPA downregulated $PKC{\alpha}$ expression and increased epidermal and hair follicle cell proliferation. Thus, $PKC{\alpha}$ downregulation is accompanied by in vivo cell proliferation, as evidenced in 7, 12-dimethylbenz(a)anthracene (DMBA)-TPA-mediated carcinogenesis. The ability of TPA to reverse senescence was further demonstrated in old HDF cells using RNA-sequencing analyses in which TPA-induced nuclear $PKC{\alpha}$ degradation freed nuclear pErk1/2 to induce cell proliferation and facilitated the recovery of mitochondrial energy metabolism. Our data indicate that TPA-induced senescence reversal and carcinogenesis promotion share the same molecular pathway. Loss of $PKC{\alpha}$ expression following TPA treatment reduces pErk1/2-activated SP1 biding to the $p21^{WAF1}$ gene promoter, thus preventing senescence onset and overcoming G1/S cell cycle arrest in senescent cells.

• The Korean Journal of Physiology and Pharmacology
• /
• v.13 no.5
• /
• pp.385-392
• /
• 2009

Angiotensin II (Ang II) plays an important role in vascular hypertension. The role of the chemokine CCL5 on Ang II-induced activities in vascular smooth muscle cells (VSMCs) has not been studied. In this study, we elucidated the effect of CCL5 on Ang II-induced 12-lipoxygenase (LO) expression and cell proliferation in spontaneously hypertensive rats (SHR) VSMCs. CCL5 decreased Ang II-induced 12-LO mRNA expression and protein production, and it increased Ang II type 2 ($AT_2$) receptor expression in SHR VSMCs. The inhibitory effect of CCL5 on Ang II-induced 12-LO mRNA expression was mediated through the $AT_2$ receptor. Although treatment of CCL5 alone induced SHR VSMCs proliferation, CCL5 inhibited Ang II-induced VSMCs proliferation and PD123,319, an $AT_2$ receptor antagonist, blocked the inhibitory effect of CCL5 on Ang II-induced VSMCs proliferation. Phosphorylation of p38 was detected in VSMCs treated with Ang II or CCL5 alone. But, decrease of p38 phosphorylation was detected in VSMCs treated with Ang II and CCL5 simultaneously (Ang II/CCL5) and PD123,319 increased p38 phosphorylation in VSMCs treated with Ang II/CCL5. Therefore, these results suggest that the inhibitory effect of CCL5 on Ang II-induced VSMCs proliferation is mediated by the $AT_2$ receptor via p38 inactivation, and CCL5 may play a beneficial role in Ang II-induced vascular hypertension.

• The Korean Journal of Physiology and Pharmacology
• /
• v.13 no.5
• /
• pp.349-356
• /
• 2009

We previously reported that glial cell line-derived neurotropic factor (GDNF) receptor ${\alpha}$ 1 (GFR ${\alpha}$ 1) is a direct target of apurinic/apyrimidinic endonuclease 1 (Ape1/Ref-1). In the present study, we further analyzed the physiological roles of Ape1/Ref-1-induced GFR ${\alpha}$ 1 expression in Neuro2a mouse neuroblastoma cells. Ape1/Ref-1 expression caused the clustering of GFR ${\alpha}$ 1 immunoreactivity in lipid rafts in response to GDNF. We also found that Ret, a downstream target of GFR ${\alpha}$ 1, was functionally activated by GDNF in Ape1/Ref-1-expressing cells. Moreover, GDNF promoted the proliferation of Ape1/Ref-1-expressing Neuro2a cells. Furthermore, GFR ${\alpha}$ 1-specific RNA experiments demonstrated that the downregulation of GFR ${\alpha}$ 1 by siRNA in Ape1/Ref-1-expressing cells impaired the ability of GDNF to phosphorylate Akt and PLC ${\gamma}$-1 and to stimulate cellular proliferation. These results show an association between Ape1/Ref-1 and GDNF/GFR ${\alpha}$ signaling, and suggest a potential molecular mechanism for the involvement of Ape1/Ref-1 in neuronal proliferation.

• Journal of Microbiology and Biotechnology
• /
• v.18 no.11
• /
• pp.1862-1867
• /
• 2008

Streptochlorin is a small molecule isolated from marine Streptomyces sp. that is known to have antiangiogenic and anticancer properties. In this study, we examined the effects of this compound on reactive oxygen species (ROS) production and the association of these effects with apoptotic tumor cell death, using a human hepatocarcinoma Hep3B cell line. The results of this study demonstrated that streptochlorin mediates ROS production, and that this mediation is followed by a decrease in the mitochondrial membrane potential (MMP, ${\Delta}{\Psi}_m$), activation of caspase-3, and downregulation of antiapoptotic Bcl-2 protein. The quenching of ROS generation by N-acetyl-L-cysteine administration, a scavenger of ROS, reversed the streptochlorin-induced apoptosis effects via inhibition of ROS production, MMP collapse, and the subsequent activation of caspase-3. These observations clearly indicate that ROS are involved in the early molecular events in the streptochlorin-induced apoptotic pathway. Taken together, our data imply that streptochlorin-induced ROS is a key mediator of MMP collapse, which leads to the caspase-3 activation, culminating in apoptosis.

• Journal of Microbiology and Biotechnology
• /
• v.24 no.1
• /
• pp.127-131
• /
• 2014

While searching for lactic acid bacteria that can restore aging-impaired immune responses, we isolated the Toll-like receptor (TLR) 2/NF-${\kappa}B$-activating strain Lactobacillus plantarum HY7712 from kimchi and investigated its immunomodulating effect in whole-body ${\gamma}$-irradiated mice. Exposure to HY7712 strongly activated NF-${\kappa}B$ signaling in RAW264.7 cells, but inhibited lipopolysaccharide-stimulated NF-${\kappa}B$ activation. Moreover, HY7712 protected against the downregulation of interferon (IFN)-${\gamma}$ and upregulation of interleukin (IL)-13 caused by ${\gamma}$-irradiation in mice. In mice, ${\gamma}$-irradiation impaired NK-cell activity against YAC-1 tumor cells, but following HY7712 exposure, the activity of NK cells was restored to 91.5% of the level measured in control mice (p < 0.05). These findings suggest that HY7712 activates the TLR2/NF-${\kappa}B$ signaling pathway and protects against the impairment of NK-cell activity caused by ${\gamma}$-irradiation or aging.

• Journal of Microbiology and Biotechnology
• /
• v.30 no.11
• /
• pp.1729-1738
• /
• 2020

Salmonellosis is a form of gastroenteritis caused by Salmonella infection. The main transmission route of salmonellosis has been identified as poorly cooked meat and poultry products contaminated with Salmonella. However, in recent years, the number of outbreaks attributed to contaminated raw produce has increased dramatically. To understand how Salmonella adapts to produce, transcriptomic analysis was conducted on Salmonella enterica serovar Virchow exposed to fresh-cut radish greens. Considering the different Salmonella lifestyles in contact with fresh produce, such as motile and sessile lifestyles, total RNA was extracted from planktonic and epiphytic cells separately. Transcriptomic analysis of S. Virchow cells revealed different transcription profiles between lifestyles. During bacterial adaptation to fresh-cut radish greens, planktonic cells were likely to shift toward anaerobic metabolism, exploiting nitrate as an electron acceptor of anaerobic respiration, and utilizing cobalamin as a cofactor for coupled metabolic pathways. Meanwhile, Salmonella cells adhering to plant surfaces showed coordinated upregulation in genes associated with translation and ribosomal biogenesis, indicating dramatic cellular reprogramming in response to environmental changes. In accordance with the extensive translational response, epiphytic cells showed an increase in the transcription of genes that are important for bacterial motility, nucleotide transporter/metabolism, cell envelope biogenesis, and defense mechanisms. Intriguingly, Salmonella pathogenicity island (SPI)-1 and SPI-2 displayed up- and downregulation, respectively, regardless of lifestyles in contact with the radish greens, suggesting altered Salmonella virulence during adaptation to plant environments. This study provides molecular insights into Salmonella adaptation to plants as an alternative environmental reservoir.

• Proceedings of the Korean Society of Food Science and Nutrition Conference
• /
• 2001.12a
• /
• pp.22-37
• /
• 2001

Melatonin is secreted during the hours of darkness and is thought to influence the circadian and seasonal timing of a variety of physiological processes. Serotonin N-acetyltransferase (AA-NAT) which is found to be expressed in pineal gland, retina, and various tissues, catalyses the conversion of serotonin to N-acetylserotonin and is known as the rate-limiting enzyme in the biosynthetic pathway of melatonin. The compounds that modulate the activity of AA-NAT can be used to treat serotonin-and melatonin-related diseases such as insomnia, depression and seasonal affective disorders (SAD). Several assay methods have been developed by which to measure AA-NAT activity. We have also developed a simple, rapid and sensitive AA-NAT assay method that takes advantage of differences in the organic solubilities between acetyl CoA and N-acetyltryptamine. We screened modulators of AA-NAT activity from the water extracts of the medicinal plants. We found MNP1005 which strongly inhibited the activity of AA-NAT ($IC_{50}$=2.2$\mu$M). Enzyme inhibitory kinetic studies revealed that MNP1005 exhibited a noncompetitive inhibition toward tryptamine. The antidepressant effect of MNP1005 was investigated on behavioral despair test so called forced swimming test (FST). MNP1005 significantly increased swimming behavior by reducing immobility with treatment of 10 mg/kg when compared to the vehicle-treated control group (P < 0.05). This suggests that MNP1005 possesses antidepressant activity. The influence of chronic MNP1005 treatment on the expression of brain-derived neurotrophic factor (BDNF) was examined by in situ hybridization and Northern blot. Chronic treatment of MNP1005 blocked the downregulation of BDNF mRNA in the frontal cortex and other cortex regions in response to restraint stress.

• Journal of Ginseng Research
• /
• v.38 no.3
• /
• pp.208-214
• /
• 2014

Background: In previous work, we reported that Korean Red Ginseng saponin fraction (RGSF) showed anti-inflammatory activities in vitro and in vivo. Methods: The present study investigated the radioprotective properties of RGSF by examining its effects on ionizing radiation (IR)-enhanced and lipopolysaccharide (LPS)-mediated inflammatory responses in murine macrophage cells. Results: RGSF induced strong downregulation of IR-enhanced and LPS-induced proinflammatory responses such as nitric oxide (NO) production (Inhibitory Concentration $50(IC_{50})=5.1{\pm}0.8{\mu}M$) and interleukin-$1{\beta}$ levels. RGSF was found to exert its radioprotective effects by inhibition of a signaling cascade that activated checkpoint kinase 2enuclear factor-${\kappa}B$. In addition, RGSF strongly inhibited IR-enhanced LPS-induced expression of hemoxyganase-1, implying that the latter may be a potential target of RGSF. Conclusion: Taken together, our data suggest that RGSF can be considered and developed for use as an effective radioprotective agent with minimal adverse effects.