• The Korean Journal of Physiology and Pharmacology
• /
• v.6 no.4
• /
• pp.199-205
• /
• 2002

The role of peripheral vestibular receptors in acute hypotension was investigated in anesthetized rats. Acute hypotension was induced by either intravenous infusion of sodium nitroprusside (SNP) or by experimental hemorrhage, and electrical activity and expression of cFos-like immunoreactive (cFL) protein were measured in the medial vestibular nuclei (MVN). Blood pressure decreased proportionately to the does of intravenous SNP and to the volume of the hemorrhage. Blood pressure decreased 10, 30, 50% for the 5, 10, $15{\mu}g/kg$ SNP injection, respectively, and also decreased 30 and 50% after 1- and 2-ml blood loss, respectively, due to hemorrhage. In animals with intact labyrinths, acute hypotension induced by either intravenous infusion of SNP or hemorrhage produced different electrical activities with three different patterns in type I and II neurons of MVN. The responses of type I neurons showed excitatory in 2/3 of recorded neurons and inhibitory or no change in 1/3 of neurons, while the responses of type II neurons showed inhibitory in 2/3 of recorded neurons and excitatory or no change in 1/3 of neurons. In unilateral labyrinthectomized animals, 2/3 of type I neurons ipsilateral to the lesion showed an inhibitory response, and 2/3 of contralateral type I neurons showed an excitatory response after the induction of acute hypotension. The response patterns of type II neurons were opposite from those of the type I neurons. After 30% decrease in blood pressure, cFL protein expressed in the bilateral vestibular nuclei of control animals with intact labyrinths. Expression of cFL protein increased significantly proportionately to the reduction of blood pressure. The unilateral labyrinthectomized animals with acute hypotension produced expression of cFL neurons in contralateral vestibular nuclei to the lesion side, but not in ipsilateral vestibular nuclei. However, cFL protein was not expressed in bilateral vestibular nuclei after acute hypotension in bilateral labyrinthectomized animals. These results suggest that the peripheral vestibular receptors might play a significant role in controlling blood pressure following acute hypotension via activation of type I neurons and inhibition of type II neurons in the vestibular nuclei.

• Journal of Life Science
• /
• v.21 no.7
• /
• pp.985-991
• /
• 2011

The purpose of this study was to investigate the biological effect of obesity-induced oxidative damage on neurogenesis and early protein expression. Obesity was induced I thirty 4-week old male Sprague-Dawley rats through a high fat diet for 15 weeks. After one week of environmental adaptation, the rats were divided into 2 groups: high fat diet sedentary group (HDS, n=15) and high fat diet training group (HDT, n=15). Exercise training was performed 5 times a week for 8 weeks, with mild-intensity treadmill running for weeks 1-4 and moderate-intensity treadmill running for weeks 5-8. After the 8 week training period, we analyzed lipid profiles, serum 8-hydroxyguanosine (8-OHdG), liver tissue malondialdehyde (MDA) related to oxidative damage factors, nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), c-fos, c-jun, and extracellular signal regulated kinase (Erk) in the hippocampus. The results of this study are as follows. There were differences between HDS and HDT in triglyceride (TG) and total cholesterol (TC) (p<0.05). In high density lipoprotein (HDL-c), the HDT was higher than HDS after treadmill training (p<0.05). In 8-OHdG, the HDT was lower than HDS after treadmill training (p<0.05). Genetic expressions of c-jun, BDNF and MDA in the HDT were higher than in the HDS after treadmill training in hippocampus (p<0.05). Therefore, we conclude that 8 weeks of treadmill training can improve imbalanced lipid profiles, reduce oxidative damage, and activate neurogenesis in obese rats.

• YAKHAK HOEJI
• /
• v.36 no.6
• /
• pp.529-537
• /
• 1992

To investigate the effect of ursolic acid on the expression of oncogenes in tumor cells of mice, sarcoma 180 ascites tumor cells were implanted into the left groin of ICR mice and the tumor bearing mice were treated with ursolic acid. The expression of oncogenes were measured by in situ hybridization method. Ursolic acid significantly reduced the expression of oncogenes in the tumor cells. Therefore, it can be said that the prestated anticarcinogenic effect of ursolic acid could be partly ascribed to the mechanism included in the oncogene´s transcription level.

• Biomolecules & Therapeutics
• /
• v.22 no.4
• /
• pp.308-313
• /
• 2014

Activator protein-1 (AP-1) is an inducible transcription factor that contributes to the generation of chronic inflammation in response to oxidative and electrophilic stress. Previous studies have demonstrated that the PI3K/Akt1 pathway plays an important role in the transcriptional regulation of AP-1 expression. Although the histone post-translational modifications (PTMs) are assumed to affect the AP-1 transcriptional regulation by the PI3K/Akt pathway, the detailed mechanisms are completely unknown. In the present study, we show that heterochromatin 1 gamma ($HP1{\gamma}$) plays a negative role in TPA-induced c-Jun and c-Fos expression. We show that TPA-induced Akt1 directly phosphorylates $HP1{\gamma}$, abrogates its suppressive function and increases the interaction between histone H3 and 14-3-$3{\varepsilon}$. Collectively, these our data illustrate that the activation of PI3K/Akt pathway may play a permissive role in the recruitment of histone readers or other coactivators on the chromatin, thereby affecting the degree of AP-1 transcription.

• International Journal of Oral Biology
• /
• v.35 no.4
• /
• pp.145-151
• /
• 2010

Periodontitis is an inflammatory disorder of the periodontium and is characterized by destruction of the tooth supporting tissues, mediated by the upregulation of synthesis and release of a variety of pro-inflammatory factors. Inflammatory cytokines and prostaglandins upregulate RANKL and its subsequent binding to RANK stimulates osteoclast formation, resorption activity, and survival. In our present study, we investigated the effects of HP08-0111, composed of Coptis japonica (Thunb.) Makino, vitamin C and vitamin E, upon inflammatory responses, osteoclastogenesis and alveolar bone loss. HP08-0111 decreased the expression of IL-1$\beta$ and COX2 on LPS-induced RAW 264.7 cells and inhibited osteoclast-specific genes such as c-Fos, MMP-9, and TRAP. HP08-0111 also exhibited protective effects against alveolar bone loss in rats with ligature-induced periodontitis. Our results suggest that HP08-0111 is potentially an important therapeutic tool for the treatment of disorders associated with bone loss such as periodontitis.

• BMB Reports
• /
• v.34 no.6
• /
• pp.517-525
• /
• 2001

Six renaturable protein kinases that utilize the myelin basic protein (MBP) as a substrate were activated during prolonged exposure of cardiac myocytes to okadaic acid (OA). We characterized the substrate preference and activation of these kinases, with particular emphasis on 3 novel kinases-MBPK-55, MBPK-62 and MBPK-87. The transcription factors c-Jun, Elk, ATF2, and c-Fos that are used to assess mitogen-activated protein kinase activation were all poor substrates for these three kinases. MAPKAPK2 was also not phosphorylated. In contrast, Histone IIIS was phosphorylated by MBPK-55 and MBPK-62. These protein kinases were activated in cultured cardiac fibroblasts, H9c2 cardiac myoblasts, and Cos cells. High concentrations (0.5 to $1\;{\mu}M$) of OA were essential for the activation of the protein kinases in all of the cell types examined, whereas calyculin A [an inhibitor of protein phosphatase 1 (PP1) and PP2A], cyclosporin A (a PP2B inhibitor), and an inactive OA analog all failed to activate these kinases. The high dose of okadaic acid that is required for kinase activation was also required for phosphatase inhibition, as assessed by immunoblotting whole cell lysates with anti-phosphothreonine antibodies. A variety of chemical inhibitors, including PD98059 (MEK-specific), genistein (tyrosine kinase-specific) and Bisindolylmaleimide I (protein kinase C-specific), failed to inhibit the OA activation of these kinases. Thus, MBPK-55 and MBPK-62 are also Histone IIIS kinases that are widely expressed and specifically activated upon exposure to high OA concentrations.

• Molecular & Cellular Toxicology
• /
• v.1 no.1
• /
• pp.52-61
• /
• 2005

Transcript profiling is a particularly valuable tool in the field of steroid receptor biology, as these receptors are ligand-activated transcription factors and therefore exert their initial effects through altering gene expression in responsive cells. Also, an awareness of endocrine disrupting chemicals (EDCs) and their potential screening methods to identify endocrine activity have been increased. Here we developed an in-house cDNA microarray, named KISTCHIP-400 ver. 1.0, with 416 clones, based on public database and research papers. These clones contained estrogen, androgen, thyroid hormone & receptors, sex hormone signal transduction & regulation, c-fos, c-myc, ps2 gene, metabolism related genes etc. Also, to validate the KISTCHIP-400 ver. 1.0, we investigated gene expression profiles with reference hormones, $10^{8}\;M\;17{\beta}-estradiol,\;10^{-7}\;M\;testosterone\;and\;10^{-7}\;M$ progesterone in MCF-7 cell line. As the results, gene expression profiles of three reference hormones were distinguished from each other with significant and identified 33 $17{\beta}-estradiol$ responsive genes. This study is in first step of validation for KISTCHIP-400 ver. 1.0, as following step transcriptional profile analysis on not only low concentrations of EDCs but suspected EDCs using KISTCHIP-400 ver. 1.0 is processing. Our results indicate that the developed microarray may be a useful laboratory tool for screening EDCs and elucidating endocrine disrupting mechanism.

• Toxicological Research
• /
• v.17
• /
• pp.83-88
• /
• 2001

Most reactive oxygen species (ROS) are free radicals and implicated in the development of a number of disease processes including artherosclerosis, neurodegenerative disorders, aging and cancer. ROS are byproducts of a number of in vivo metabolic processes and are formed deliberately as part of nor-mal inflammatory response. On the other hand, ROS are generated either as by products of oxygen reduction during xenobiotic metabolism or are liberated as the result of the futile redox cycling of the chemical agents including several chemical carcinogens. A better understanding of the mechanisms of free radical toxicity may yield valuable clue to risks associated with chemical exposures that leading to the development of chronic diseases including cancer. The molecular biology of ROS-mediated alterations in gene expression, signal transduction and carcinognesis is one of the important subjects in free radical toxicology. Epidemiological studies suggest that high intake of vegetables and fruits are associated with the low incidence of human cancer. Many phytopolyphenols such as tea polyphenols, curcumin, resveratrol, apigenin, genistein and other flavonoids have been shown to be cancer chemopreventive agents. Most of these compounds are strong antioxidant and ROS scavengers in vitro and effective inducers of antioxidant enzymes such as superoxide dismutatse, catalase and glutathione peroxidase in vivo. Several cellular transducers namely receptor tyrosine kinase, protein kinase C, MAPK, PI3K, c-jun, c-fos, c-myc, NFkB, IkB kinase, iNOS, COX-2, Bcl-2, Bax, etc have been shown to be actively modulated by phyto-polyphenols. Recent development in free radical toxicology have provided strong basis for understanding the action mechanisms of cancer chemoprevention.

• Proceedings of the Korea Society of Environmental Toocicology Conference
• /
• 2003.05a
• /
• pp.180-180
• /
• 2003

Transcript profiling is a particularly valuable tool in the field of steroid receptor biology, as these receptors are ligand-activated transcription factors and therefore exert their initial effects through altering gene expression in responsive cells. Also, an increased awareness of endocrine disrupting chemicals (EBCs) and their potential to affect wildlife and humans has produced a demand for practical screening methods to identify endocrine activity. Here we developed an in-house cDNA microarray, named KISTCHIP-400, with 401 clones, hormone related genes, factors, and ESTs, based on public database and research papers. Theses clones contained estrogen, androgen, thyroid hormone St receptors, sex hormone signal transduction ＆ regulation, c-fos, c-myc, ps2 gene, metabolism related genes etc. And to validate the KISTCHIP-400, we investigated gene expression profiles with reference hormones, 10$\^$-8/ M 17be1a-estradiol, 10$\^$-7/ M testosterone, 10$\^$-7/ M progesterone, and thyroxin in MCF-7 cell line. Although it is in first step of validation, low doses and combinations of EDCs need to be tested. Our preliminary results that indicate the developed microarray may be a useful laboratory tool for screening EDCs and elucidating endocrine disrupting mechanism.

• The Korean Journal of Physiology and Pharmacology
• /
• v.9 no.5
• /
• pp.299-304
• /
• 2005

Cardiac hypertrophy contributes an increased risk to major cerebrovascular events. However, the molecular mechanisms underlying cerebrovascular dysfunction during cardiac hypertrophy have not yet been characterized. In the present study, we examined the molecular mechanism of isoproterenol (ISO)-evoked activation of Ras/Raf/MAPK pathways as well as PKA activity in cerebral artery of rabbits, and we also studied whether the activations of these signaling pathways were altered in cerebral artery, during ISO-induced cardiac hypertrophy compared to heart itself. The results show that the mRNA level of c-fos (not c-jun and c-myc) in heart and these genes in cerebral artery were considerably increased during cardiac hypertrophy. These results that the PKA activity and activations of Ras/Raf/ERK cascade as well as c-fos expression in rabbit heart during cardiac hypertrophy were consistent with previous reports. Interestingly, however, we also showed a novel finding that the decreased PKA activity might have differential effects on Ras and Raf expression in cerebral artery during cardiac hypertrophy. In conclusion, there are differences in molecular mechanisms between heart and cerebral artery during cardiac hypertrophy when stimulated with β2 adrenoreceptor (AR), suggesting a possible mechanism underlying cerebrovascular dysfunction during cardiac hypertrophy.