• The Korean Journal of Physiology and Pharmacology
• /
• v.20 no.4
• /
• pp.325-332
• /
• 2016

Resveratrol, a phytoalexin, is reported to activate AMP-activated protein kinase (AMPK) in vascular cells. The blood-brain barrier (BBB), formed by specialized brain endothelial cells that are interconnected by tight junctions, strictly regulates paracellular permeability to maintain an optimal extracellular environment for brain homeostasis. The aim of this study was to elucidate the effects of resveratrol and the role of AMPK in BBB dysfunction induced by lipopolysaccharide (LPS). Exposure of human brain microvascular endothelial cells (HBMECs) to LPS ($1{\mu}g/ml$) for 4 to 24 hours week dramatically increased the permeability of the BBB in parallel with lowered expression levels of occluding and claudin-5, which are essential to maintain tight junctions in HBMECs. In addition, LPS significantly increased the reactive oxygen species (ROS) productions. All effects induced by LPS in HBVMCs were reversed by adenoviral overexpression of superoxide dismutase, inhibition of NAD(P) H oxidase by apocynin or gain-function of AMPK by adenoviral overexpression of constitutively active mutant (AMPK-CA) or by resveratrol. Finally, upregulation of AMPK by either AMPK-CA or resveratrol abolished the levels of LPS-enhanced NAD(P)H oxidase subunits protein expressions. We conclude that AMPK activation by resveratrol improves the integrity of the BBB disrupted by LPS through suppressing the induction of NAD(P)H oxidase-derived ROS in HBMECs.

• YAKHAK HOEJI
• /
• v.60 no.1
• /
• pp.8-14
• /
• 2016

Endotoxemia induces production of inflammatory mediators and acute phase proteins, leading to multiorgan injury and systemic inflammation. Hypothalamic-pituitary-adrenal (HPA) axis activation and glucocorticoids (GCs) release modify endotoxemia-induced inflammatory responses. In the present study, we investigated whether pre-exposure of GCs influences endotoxin-induced production of inflammatory mediators in hepatocytes. Hepa1c1c-7 cells were pretreated with low concentrations of corticosterone for 24 h and then cultured without corticosterone in the presence or absence of LPS. Our results demonstrated that LPS alone significantly enhanced production of IL-6 and CRP but reduced vascular endothelial growth factor (VEGF) compared to controls. Combination of corticosterone pretreatment and LPS significantly upregulated production of IL-6, IL-$1{\beta}$, and VEGF but downregulated CRP compared to those in LPS alone. These findings suggest that in low concentration of corticosterone-preexposed hepatocytes, endotoxemia may induce upregulation of IL-6, IL-$1{\beta}$, VEGF and but downregulation of CRP.

• IMMUNE NETWORK
• /
• v.2 no.1
• /
• pp.6-11
• /
• 2002

Background: Inflammation is a frequent reaction following therapeutic irradiation. Since the upregulation of adhesion molecules on endothelial cell surface is known to be associated with inflammation, the expression of adhesion molecules is an important therapeutic target. Methods: Treatment of human umbilical endothelial cells (HUVECs) with ${\gamma}$-irradiation (${\gamma}IR$) induces the expression of adhesion proteins such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. Changes in the expression of these proteins on ${\gamma}$-irradiated HUVECs which had been treated previously with allicin were measured by ELISA. Results: In the present study, we demonstrate that allicin inhibits the ${\gamma}IR$ induced expression of ICAM-1, VCAM-1, and E-selectin on HUVEC in a dose-dependent manner. Allicin was also found to inhibit the ${\gamma}IR$ induced production of nitric oxide (NO). Conclusion: These data suggest that allicin has a therapeutic potential for the treatment of various inflammatory disorders associated with increase numbers of endothelial leukocyte adhesion molecules.

• Journal of Acupuncture Research
• /
• v.30 no.1
• /
• pp.43-55
• /
• 2013

I investigated whether snake venom toxin(SVT) from Vipera lebetina turanica enhances the apoptosis ability of tumor necrosis factor(TNF)-related apoptosis-inducing ligand(TRAIL) in cancer cells. TRAIL inhibited HCT116 cell growth in a dose-dependent manner. Consistent with cell growth inhibition, the expression of TRAIL receptors; DR4 and DR5 was significantly increased as well as apoptosis related proteins such as cleaved caspase-3, 8, 9 and Bax. However, the expression of survival proteins(eg, cFLIP, survivin, XIAP and Bcl2) was suppressed by the combination treatment of SVT and TRAIL. Pretreatment with the reactive oxygen species(ROS) scavenger N-acetylcysteine reduced the SVT and TRAIL-induced upregulation of DR4 and DR5 expression and expression of the apoptosis related protein such as caspase-3 and-9 as well as cell growth inhibitory effects. The collective results suggest that SVT facilitates TRAIL-induced apoptosis in human colorectal cancer HCT116 cells through up-regulation of the TRAIL receptors; DR4 and DR5 via ROS pathway signals.

• Journal of Acupuncture Research
• /
• v.30 no.1
• /
• pp.57-70
• /
• 2013

This study was to investigated the effects of the bee venom on inhibition of cell growth via upregulation of death receptor expression in the A549 human lung cancer cells. Bee venom(1-5 ${\mu}g$/ml) inhibited the growth of A549 lung cancer cells by the induction of apoptotic cell death in a dose dependent manner. Consistent with apoptotic cell death, expression of TNFR1, Fas, death receptors(DR) 3, 4 and 6 was increased in the cells. Expression of DR downstream pro-apoptotic proteins including caspase-3, -9 and Bax was concomitantly increased, but the expression of Bcl-2, NF-${\kappa}B$ were inhibited by treatment with bee venom in A549 cells. Moreover, deletion of DR3, DR4 by small interfering RNA significantly reversed bee venom-induced cell growth inhibitory effect, whereas Apo3L strengthened anti-proliferative effect of bee venom through enhancement of DR3 expression. These results suggest that bee venom should exert anti-tumor effect through induction of apoptotic cell death in lung cancer cells via enhancement of death receptor expression, and that bee venom could be a promising agent for preventing and treating lung cancer.

• Biomedical Science Letters
• /
• v.26 no.1
• /
• pp.37-41
• /
• 2020

The hemolymph of Korean rhinoceros Allomyrina dichotoma consists of blood and lymph in which various kinds of proteins function physiologically. We have previously demonstrated that A. dichotoma hemolymph has the potential to treatment and prevent diabetes through activating transcription factor 3-gene (ATF3) regulation. In this study, we investigate the expression of Kruppel-like factor 4 (KLF4) in A. dichotoma hemolymph-treated INS-1 pancreatic β-cells. The new findings show that A. dichotoma hemolymph, which upregulates KLF4 gene expression in a dose-dependent and time-dependent manner. In addition, hemolymph combine with mild endoplasmic reticulum (ER) stress, which also differentially regulates KLF4 gene expression. These results may provide insights to KLF4 gene-related disease therapies through KLF4 gene regulation.

• Journal of Ginseng Research
• /
• v.39 no.4
• /
• pp.299-303
• /
• 2015

Panax ginseng is a well-known economic medical plant that is widely used in Chinese traditional medicine. This species contains a unique class of natural products-ginsenosides. Recent clinical and experimental studies have presented numerous lines of evidence on the promising role of ginsenosides on different diseases including neurodegenerative diseases, cardiovascular diseases, and certain types of cancer. Nowadays, most of the attention has focused on ginsenoside Rd as a neuroprotective agent to attenuate ischemic stroke damages. Some of the evidence showed that ginsenoside Rd ameliorates ischemic stroke-induced damages through the suppression of oxidative stress and inflammation. Ginsenoside Rd can prolong neural cells' survival through the upregulation of the endogenous antioxidant system, phosphoinositide-3-kinase/AKT and extracellular signal-regulated protein kinase 1/2 pathways, preservation of mitochondrial membrane potential, suppression of the nuclear factor-kappa B, transient receptor potential melastatin, acid sensing ion channels 1a, poly(ADP-ribose) polymerase-1, protein tyrosine kinase activation, as well as reduction of cytochrome c-releasing and apoptosis-inducing factor. In the current work, we review the available reports on the promising role of ginsenoside Rd on ischemic stroke. We also discuss its chemistry, source, and the molecular mechanism underlying this effect.

• Journal of the Korea Society of Computer and Information
• /
• v.21 no.12
• /
• pp.139-145
• /
• 2016

In this paper, we propose to evaluate the effect of Resistin-like molecule alpha (Retnla) on the expression of transporters involved in modulating concentrations of peripheral cholesterol and plasma high-density lipoprotein (HDL) cholesterol. High levels of blood cholesterol are a well-recognized risk factor for atherosclerosis and are eliminated via the process of reverse cholesterol transport (RCT). We recently showed that Retnla ameliorates hypercholesterolemia and atherosclerosis by increasing biliary cholesterol secretion, the final step of the process, in low-density lipoprotein receptor-deficient mice. However, the role of Retnla in HDL-mediated cholesterol efflux, initial step of RCT pathway, is not yet clear. To identify cholesterol transport genes regulated by Retnla, we performed an extensive microarray-based gene expression screen using livers from Retnla-overexpressing (Tg) mice and control animals. The most significant change in Retnla-Tg mice was an upregulation of ATP-binding cassette sub-family G member 4 (Abcg4) transport and was validated using quantitative RT-PCR. The validated gene was also induced by treatment of purified Retnla protein in RAW 264.7 cells incubated with acetylated low-density lipoprotein and Hepa1c1c7 cells. Taken together, these results indicates that Retnla might also accelerate initial step of RCT pathway, suggesting therapeutic value of Retnla in the treatment of hypercholesterolemia and atherosclerosis.

• Archives of Pharmacal Research
• /
• v.26 no.5
• /
• pp.405-410
• /
• 2003

Vitamin K-related analogs induce growth inhibition in various cancer cell lines. A naphthoquinone analog, termed 2,3-dichloro-5, 8-dihydroxy-1,4-naphthoquinone (DDN), induces apoptosis in human promyeloid leukemic HL-60 cells, and shows antitumor activity in vivo. Following treatment with DDN, evidence of apoptosis, including DNA fragmentation and cleavage of poly ADP ribose polymerase (PARP), was observed. DDN induced an upregulation of proapoptotic Bax protein, and Bid cleavage. Antiapoptotic Bcl-2 protein levels were not changed by DDN, but the expression of Bcl-xL was decreased. In addition, DDN reduced the mass of solid tumor in the Sarcoma 180 tumor-bearing mouse model. These results indicate that DDN exerts antitumor activity, which appears to be related to the induction of apoptosis by regulating Bcl-2 family proteins.

• Clinical and Experimental Reproductive Medicine
• /
• v.47 no.2
• /
• pp.94-100
• /
• 2020

The inverse correlation between maternal age and pregnancy rate represents a major challenge for reproductive endocrinology. The high embryo ploidy error rate in failed in vitro fertilization (IVF) cycles reflects genetic misfires accumulated by older oocytes over time. Despite the application of different follicular recruitment protocols during IVF, gonadotropin modifications are generally futile in addressing such damage. Even when additional oocytes are retrieved, quality is frequently poor. Older oocytes with serious cytoplasmic and/or chromosomal errors are often harvested from poorly perfused follicles, and ovarian vascularity and follicular oxygenation impact embryonic chromosomal competency. Because stimulation regimens exert their effects briefly and immediately before ovulation, gonadotropins alone are an ineffective antidote to long-term hypoxic pathology. In contrast, the tissue repair properties (and particularly the angiogenic effects) of platelet-rich plasma (PRP) are well known, with applications in other clinical contexts. Injection of conventional PRP and/or its components (e.g., isolated platelet-derived growth factors as a cell-free substrate) into ovarian tissue prior to IVF has been reported to improve reproductive outcomes. Any derivative neovascularity may modulate oocyte competence by increasing cellular oxygenation and/or lowering concentrations of intraovarian reactive oxygen species. We propose a mechanism to support intrastromal angiogenesis, improved follicular perfusion, and, crucially, embryo ploidy rescue. This last effect may be explained by mRNA upregulation coordinated by PRP-associated molecular signaling, as in other tissue systems. Additionally, we outline an intraovarian injection technique for platelet-derived growth factors and present this method to help minimize reliance on donor oocytes and conventional hormone replacement therapy.