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Hoon Ryu

Publications and source records attributed to Hoon Ryu.

36 records · Page 2Linked to original sources
PubMed2004

ASC is a Bax adaptor and regulates the p53-Bax mitochondrial apoptosis pathway.

The apoptosis-associated speck-like protein (ASC) is an unusual adaptor protein that contains the Pyrin/PAAD death domain in addition to the CARD protein-protein interaction domain. Here, we present evidence that ASC can function as an adaptor molecule for Bax and regulate a p53-Bax mitochondrial pathway of apoptosis. When ectopically expressed, ASC interacted directly with Bax, colocalized with Bax to the mitochondria, induced cytochrome c release with a significant reduction of mitochondrial membrane potential and resulted in the activation of caspase-9, -2 and -3. The rapid induction of apoptosis by ASC was not observed in Bax-deficient cells. We also show that induction of ASC after exposure to genotoxic stress is dependent on p53. Blocking of endogenous ASC expression by small-interfering RNA (siRNA) reduced the apoptotic response and inhibited translocation of Bax to mitochondria in response to p53 or genotoxic insult, suggesting that ASC is required to translocate Bax to the mitochondria. Our findings demonstrate that ASC has an essential role in the intrinsic mitochondrial pathway of apoptosis through a p53-Bax network.

Apoptosis↗
PubMed2004

Genetic and pharmacological inactivation of the adenosine A2A receptor attenuates 3-nitropropionic acid-induced striatal damage.

Adenosine A2A receptor (A2AR) antagonism attenuates 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurodegeneration and quinolinic acid-induced excitotoxicity in the neostriatum. As A2ARs are enriched in striatum, we investigated the effect of genetic and pharmacological A2A inactivation on striatal damage produced by the mitochondrial complex II inhibitor 3-nitropriopionic acid (3-NP). 3-NP was administered to A2AR knockout (KO) and wild-type (WT) littermate mice over 5 days. Bilateral striatal lesions were analyzed from serial brain tissue sections. Whereas all of the 3-NP-treated WT mice (C57BL/6 genetic background) had bilateral striatal lesions, only one of eight of the 3-NP-treated A2AR KO mice had detectable striatal lesions. Similar attenuation of 3-NP-induced striatal damage was observed in A2AR KO mice in a 129-Steel background. In addition, the effect of pharmacological antagonism on 3-NP-induced striatal neurotoxicity was tested by pre-treatment of C57Bl/6 mice with the A2AR antagonist 8-(3-chlorostyryl) caffeine (CSC). Although bilateral striatal lesions were observed in all mice treated either with 3-NP alone or 3-NP plus vehicle, there were no demonstrable striatal lesions in mice treated with CSC (5 mg/kg) plus 3-NP and in five of six mice treated with CSC (20 mg/kg) plus 3-NP. We conclude that both genetic and pharmacological inactivation of the A2AR attenuates striatal neurotoxicity produced by 3-NP. Since the clinical and neuropathological features of 3-NP-induced striatal damage resemble those observed in Huntington's disease, the results suggest that A2AR antagonism may be a potential therapeutic strategy in Huntington's disease patients.

Adenosine A2 Receptor Antagonists↗
PubMed2004

Endocrine and immune effects of Qi-training.

Psychoneuroimmunological approaches have shown that Qi-training influences the holistic health state in men. We found that Qi-training increased the plasma level of growth hormone (GH) and insulin-like growth factor (IGF)-I. In addition, the respiratory function and adhesion capacity of neutrophil was increased after Qi-training. In an in vitro analysis, GH primed and increased the respiratory function and adhesion of neutrophils through tyrosin kinase passway. Taken together, in vivo and in vitro data suggest that the beneficial effects of Qi-training on immunological functions are mediated via neuroendocrine responses.

Adult↗
PubMed2004

Qi-training enhances neutrophil function by increasing growth hormone levels in elderly men.

This article investigated the effects of Qi-training on the neuroendocrine response and superoxide generation by neutrophils in healthy elderly men. One hour of Qi-training significantly reduced the plasma concentration of cortisol, and increased plasma concentrations of growth hormone and melatonin. Generation of superoxide by neutrophils increased significantly immediately after Qi-training (p < .01). The change in neutrophil superoxide generation was significantly correlated with the change in growth hormone concentration after Qi-training (p < .01). These data indicate that, in elderly men, Qi-training enhances superoxide generation by neutrophils, possibly via the changes in plasma growth hormone concentration.

Aged↗
PubMed2004

Effect of qi training on neutrophil function in young and elderly males.

OBJECTIVES: To examine the effect of qi training on neutrophil bactericidal function (superoxide generation and adhesion). METHODS: We studied the effects of one session of qi training on superoxide generation and adhesion of neutrophils immediately after (Post I), and 2 hours after qi training (Post II), in nine young and nine elderly male subjects. RESULTS: The qi training significantly enhanced the superoxide generation and adhesion of neutrophils, and there were significant differences at Post I compared to before qi training (Pre) in both groups. CONCLUSION: Our current observations show that qi training enhances superoxide generation and adhesion of neutrophils. It is supposed that qi training may increase the resistance of trained individuals against common infection and inflammation.

Adult↗
PubMed2004

Effects of Qi-training (Qigong) on forearm blood gas concentrations.

Using an ABA' design, the authors investigated the effects of Qi-training on blood gas concentrations with a 20 min control rest period (A), 1 h of Qi-training (B), and a 20-min rest period (A'). The blood partial pressures of oxygen (PO2) and carbon dioxide (PCO2), and oxygen content, oxygen saturation, and pH were significantly altered. The mean PO2 value increased significantly during Qi-training by 14 mmHg (about 24%, p < .01) compared with control A. During Qi-training, the mean decrease in PCO2 was 3 mmHg (about 10%). These results suggest that the practical application of Qi-training may exert a positive regulatory function on physiological status.

Adult↗
PubMed2003

Histone deacetylase inhibition by sodium butyrate chemotherapy ameliorates the neurodegenerative phenotype in Huntington's disease mice.

The precise cause of neuronal death in Huntington's disease (HD) is unknown. Although no single specific protein-protein interaction of mutant huntingtin has emerged as the pathologic trigger, transcriptional dysfunction may contribute to the neurodegeneration observed in HD. Pharmacological treatment using the histone deacetylase inhibitor sodium butyrate to modulate transcription significantly extended survival in a dose-dependent manner, improved body weight and motor performance, and delayed the neuropathological sequelae in the R6/2 transgenic mouse model of HD. Sodium butyrate also increased histone and Specificity protein-1 acetylation and protected against 3-nitropropionic acid neurotoxicity. Microarray analysis showed increased expression of alpha- and beta-globins and MAP kinase phosphatase-1 in sodium butyrate-treated R6/2 mice, indicative of improved oxidative phosphorylation and transcriptional regulation. These findings strengthen the hypothesis that transcriptional dysfunction plays a role in the pathogenesis of HD and suggest that therapies aimed at modulating transcription may target early pathological events and provide clinical benefits to HD patients.

Acetylation↗
PubMed2003

Molecular basis of vitamin E action: tocotrienol modulates 12-lipoxygenase, a key mediator of glutamate-induced neurodegeneration.

Vitamin E is a generic term for tocopherols and tocotrienols. This work is based on our striking evidence that, in neuronal cells, nanomolar concentrations of alpha-tocotrienol, but not alpha-tocopherol, block glutamate-induced death by suppressing early activation of c-Src kinase (Sen, C. K., Khanna, S., Roy, S., and Packer, L. (2000) J. Biol. Chem. 275, 13049-13055). This study on HT4 and immature primary cortical neurons suggests a central role of 12-lipoxygenase (12-LOX) in executing glutamate-induced neurodegeneration. BL15, an inhibitor of 12-LOX, prevented glutamate-induced neurotoxicity. Moreover, neurons isolated from 12-LOX-deficient mice were observed to be resistant to glutamate-induced death. In the presence of nanomolar alpha-tocotrienol, neurons were resistant to glutamate-, homocysteine-, and l-buthionine sulfoximine-induced toxicity. Long-term time-lapse imaging studies revealed that neurons and their axo-dendritic network are fairly motile under standard culture conditions. Such motility was arrested in response to glutamate challenge. Tocotrienol-treated primary neurons maintained healthy growth and motility even in the presence of excess glutamate. The study of 12-LOX activity and metabolism revealed that this key mediator of glutamate-induced neurodegeneration is subject to control by the nutrient alpha-tocotrienol. In silico docking studies indicated that alpha-tocotrienol may hinder the access of arachidonic acid to the catalytic site of 12-LOX by binding to the opening of a solvent cavity close to the active site. These findings lend further support to alpha-tocotrienol as a potent neuroprotective form of vitamin E.

Animals↗
PubMed2003

Sp1 and Sp3 are oxidative stress-inducible, antideath transcription factors in cortical neurons.

Neuronal cell death in response to oxidative stress may reflect the failure of endogenous adaptive mechanisms. However, the transcriptional activators induced by oxidative stress in neurons that trigger adaptive genetic responses have yet to be fully elucidated. We report that basal DNA binding of the zinc finger transcription factors Sp1 and Sp3 is unexpectedly low in cortical neurons in vitro and is significantly induced by glutathione depletion-induced or hydrogen peroxide-induced oxidative stress in these cells. The increases in Sp1/Sp3 DNA binding reflect, in part, increased levels of Sp1 and Sp3 protein in the nuclei of cortical neurons. Similar induction of Sp1 and Sp3 protein is also observed in neurons in vivo in a chemical or a genetic model of Huntington's disease, two rodent models in which neuronal loss has been attributed to oxidative stress. Sustained high-level expression of full-length Sp1 or full-length Sp3, but not the Sp1 zinc finger DNA-binding domain alone, prevents death in response to oxidative stress, DNA damage, or both. Taken together, these results establish Sp1 and Sp3 as oxidative stress-induced transcription factors in cortical neurons that positively regulate neuronal survival.

Animals↗
PubMed2003

Translational control of inducible nitric oxide synthase expression by arginine can explain the arginine paradox.

L-Arginine is the only endogenous nitrogen-containing substrate of NO synthase (NOS), and it thus governs the production of NO during nervous system development as well as in disease states such as stroke, multiple sclerosis, Parkinson's disease, and HIV dementia. The "arginine paradox" refers to the dependence of cellular NO production on exogenous L-arginine concentration despite the theoretical saturation of NOS enzymes with intracellular L-arginine. Herein, we report that decreased availability of L-arginine blocked induction of NO production in cytokine-stimulated astrocytes, owing to inhibition of inducible NOS (iNOS) protein expression. However, activity of the promoter of the iNOS gene, induction of iNOS mRNA, and stability of iNOS protein were not inhibited under these conditions. Our results indicate that inhibition of iNOS activity by arginine depletion in stimulated astrocyte cultures occurs via inhibition of translation of iNOS mRNA. After stimulation by cytokines, uptake of L-arginine negatively regulates the phosphorylation status of the eukaryotic initiation factor (eIF2 alpha), which, in turn, regulates translation of iNOS mRNA. eIF2 alpha phosphorylation correlates with phosphorylation of the mammalian homolog of yeast GCN2 eIF2 alpha kinase. As the kinase activity of GCN2 is activated by phosphorylation, these findings suggest that GCN2 activity represents a proximal step in the iNOS translational regulation by availability of l-arginine. These results provide an explanation for the arginine paradox for iNOS and define a distinct mechanism by which a substrate can regulate the activity of its associated enzyme.

Animals↗
PubMed2003

Modulation of p53 and p73 levels by cyclin G: implication of a negative feedback regulation.

Cyclin G is a transcriptional target gene of tumor suppressor p53. Recent studies present evidence that cyclin G may play a central role in the p53-Mdm2 autoregulated module, but the precise function of cyclin G remains elusive. Here, we show a negative effect of cyclin G on the stability of p53 and p73. Cyclin G expression resulted in a dramatic decrease of p53 protein levels in response to DNA damage and abrogated irradiation-mediated G1 arrest along with an increase of S phase in MCF7 cells containing wild-type p53. In p53-null Saos2 cells, cyclin G inhibited p73 induction in response to genotoxic stress and delayed the camptothecin-mediated cell cycle arrest. Cyclin G interacts with p53 as well as p73, and its binding to p53 or p73 presumably mediates downregulation of p53 and p73. We also found that cyclin G-mediated reduction of p53 but not of p73 is Mdm2-dependent. Moreover, inhibition of cyclin G by small interfering RNA (siRNA) caused the accumulation of p53 and p73 protein levels in response to DNA damage. Therefore, our results imply that cyclin G is transcriptionally activated by p53 or p73, and, in turn, cyclin G negatively regulates the stabilization of p53 family proteins through an unknown mechanism different from ubiquitination or transcriptional control.

Blotting, Northern↗
PubMed2003

Histone deacetylase inhibitors prevent oxidative neuronal death independent of expanded polyglutamine repeats via an Sp1-dependent pathway.

Oxidative stress is believed to be an important mediator of neurodegeneration. However, the transcriptional pathways induced in neurons by oxidative stress that activate protective gene responses have yet to be fully delineated. We report that the transcription factor Sp1 is acetylated in response to oxidative stress in neurons. Histone deacetylase (HDAC) inhibitors augment Sp1 acetylation, Sp1 DNA binding, and Sp1-dependent gene expression and confer resistance to oxidative stress-induced death in vitro and in vivo. Sp1 activation is necessary for the protective effects of HDAC inhibitors. Together, these results demonstrate that HDAC inhibitors inhibit oxidative death independent of polyglutamine expansions by activating an Sp1-dependent adaptive response.

Acetylation↗
PubMed2003

Qi-training enhances respiratory burst function and adhesive capacity of neutrophils in young adults: a preliminary study.

The main objective of this study is to examine the effect of Qi-training on the immune system, especially neutrophil bactericidal function. Nine healthy male subjects were studied for the effects of one bout of ChunDoSunBup (CDSB) Qi-training on superoxide (O2- production and adhesion capacity of neutrophils at times immediately after (Post I) and 2 hours after the Qi-training (Post II). The Qi-training enhanced O2- production, reaction velocity and neutrophil adhesion capacity and there were significant differences at Post I compared to before Qi-training (Pre). In addition, the number of white blood cells (WBC), monocytes and lymphocytes were changed significantly through Qi-training.Therefore, it seems that CDSB Qi-training may increase the resistance of trained individuals against common infection and inflammation.

Adult↗
PubMed2003

Effects of Qigong on immune cells.

The aim of this study was to investigate the influence of two acute Qigong interventions (Qi-training and Qi-therapy) on immune cells. The Qigong interventions were compared with placebo training and placebo therapy in which no attempt was made to gather or move Qi. Immune cell numbers were measured pre-intervention, immediately post-intervention and 1 or 2 hours post-intervention. White blood cells increased significantly 2 hours after actual Qi-training (p < 0.05) but not sham training compared with pre-intervention There were significant increases in lymphocytes 2 hours after actual but not sham Qi-training (p < 0.05) and monocyte numbers were significantly increased immediately after both actual Qi-training (p < 0.01) and sham training (p < 0.05). NK cell numbers decreased significantly both immediately after Qi-training and after sham movements done without concomitant Qi-training (p < 0.01). There were no significant effects on neutrophils. Actual Qi-therapy but not sham therapy increased monocyte numbers immediately after Qi-therapy, and lymphocytes increased more after real than after sham therapy. Neutrophils were again little changed The data indicate that a single Qigong intervention can increase the monocyte and lymphocyte numbers.

Breathing Exercises↗
PubMed2003

Effects of in vitro and in vivo Qi-therapy on neutrophil superoxide generation in healthy male subjects.

The present study investigated the effects of in vitro and in vivo Korean ChunSoo Qi-Energy Healing on neutrophil superoxide generation. Neutrophil superoxide generation was measured by a chemiluminescence assay. Superoxide generation was significantly increased in vitro by emitted Qi-therapy (QT) of 60-second duration and 150-second duration compared to control (1.59-fold for 60 seconds, p < 0.05; 1.50-fold for 150 seconds, p < 0.05). Neutrophil superoxide generation increased significantly immediately after 5 minutes of QT in vivo (1.42-fold, p < 0.05). These results show that QT in vivo and in vitro has an acute stimulatory effect on neutrophil superoxide generation. This study provides direct scientific support that Qi as such may positively affect human innate immunity.

Adult↗
PubMed2002

Depletion of intracellular glutathione mediates zinc-induced cell death in rat primary astrocytes.

In the present study, we investigated the possible mechanisms of cellular injury induced by zinc in rat primary astrocytes and C6 glioma cells. Reactive oxygen species (ROS) production, cellular glutathione (GSH) level and mitochondrial transmembrane potential were examined. Exposure to 200-300 microM Zn2+ for 24 h resulted in significant lactate dehydrogenase (LDH) release in rat primary astrocytes and C6 glioma cells. An exposure of 200 microM Zn2+ resulted in profound morphological changes, for example, shrunken and fragmented nuclei. Pretreatment of a protein synthesis inhibitor, cycloheximide, did not attenuate cellular toxicity induced by Zn2+. Zn2+ exposure increased intracellular ROS levels by about 250%, and depleted cellular GSH within 2 h, which preceded observable LDH release from the cell. Addition of GSH, N-acetylcysteine (NAC) and ascorbic acid substantially attenuated cellular death induced by Zn+ in a concentration dependent manner. ROS production and morphological changes induced by zinc were also inhibited by co-treatment of GSH or NAC with Zn2+. Zn2+ significantly depolarized mitochondrial transmembrane potential, which was reversed by co-treatment of GSH or NAC with zinc. In summary, ROS generation, GSH depletion and mitochondrial dysfunction may be key factors in Zn2+-induced glial toxicity.

Animals↗
PubMed2002

Effects of Qi-training on heart rate variability.

This study investigates changes in autonomic nervous function through Qi-training. The power spectrum of heart rate variability (HRV) was examined in 20 sedentary healthy subjects and 20 Qi-trainees. It was found that Qi-training in healthy young subjects during controlled respiration increases the high frequency (HF) power and decreases the low frequency/high frequency (LF/HF) power ratio of HRV. These results support the hypothesis that Qi-training increases cardiac parasympathetic tone. In addition, Qi-trainees were found to have higher parasympathetic heart modulation compared with their age-matched, sedentary counterparts. This augmented HRV in Qi-trainees provides further support for long-term Qi-training as a possible non-pharmacological cardio-protective maneuver. In conclusion, Qi-training may stabilize the autonomic nervous system by modulating the parasympathetic nervous system.

Adult↗