• Proceedings of the Korean Society of Life Science Conference
• /
• 2003.10a
• /
• pp.130-130
• /
• 2003

• BMB Reports
• /
• v.37 no.6
• /
• pp.753-756
• /
• 2004

Membranes prepared from Bacillus cereus KCTC 3674, grown aerobically on a complex medium, oxidized NADH exclusively, whereas deamino-NADH was little oxidized. The respiratory chain-linked NADH oxidase exhibited an apparent $K_m$ value of approximately $65\;{\mu}m$ for NADH. The maximum activity of the NADH oxidase was obtained at about pH 8.5 in the presence of 0.1 M KCl (or NaCl). Respiratory chain inhibitor 2-heptyl-4-hydroxyquinoline-N-oxide (HQNO) inhibited the activity of the NADH oxidase by about 90% at a concentration of $40\;{\mu}m$. Interestingly, rotenone and capsaicin inhibited the activity of the NADH oxidase by about 60% at a concentration of $40\;{\mu}m$ and the activity was also highly sensitive to $Ag^+$.

• Biomolecules & Therapeutics
• /
• v.4 no.4
• /
• pp.385-390
• /
• 1996

General pharmacological properties of urinary trypsin inhibitor (UTI) following intravenous administration of 1,000,000 units/kg were examined in terms of effects on central nervous system, cardiovascular system, respiratory system, gastrointestinal system in mice, rats and rabbits. Administration of UTI (1,000,000 units/kg, iv) had no effect on central nervous system; no influences on pentobarbital sleeping time, spontaneous activity, normal body temperature, chemoshock produced by pentylenetetrazole solution, writhing syndromes induced by 0.6% acetic acid solution, and motor coordination of mice. The administration of UTI (1,000,000) units/kg, iv) in rats had no effect on systolic blood pressure and pulse rate. UTI (500,000 units/kg, iv) given to anesthetized rabbits showed no effect on respiratory rate. However, it showed significant elevation of respiratory rate at the concentration of 1,000,000 units/kg. Gastric secretion of rat and intestinal motility of mice were not influenced by the dose of 1,000,000 units/kg. In terms of autonomic nervous system, the material did not show direct effect and inhibitory or augmentative action of histamine- or acetylcholine-induced contraction at the concentration of 2,000 units/ml in the isolated ileum of guinea pig.

• Tuberculosis and Respiratory Diseases
• /
• v.79 no.4
• /
• pp.248-256
• /
• 2016

Somatic mutations that lead to hyperactivation of epidermal growth factor receptor (EGFR) signaling are detected in approximately 50% of lung adenocarcinoma in people from the Far East population and tyrosine kinase inhibitors are now the standard first line treatment for advanced disease. They have led to a doubling of progression-free survival and an increase in overall survival by more than 2 years. However, emergence of resistant clones has become the primary cause for treatment failure, and has created a new challenge in the daily management of patients with EGFR mutations. Identification of mechanisms leading to inhibitor resistance has led to new therapeutic modalities, some of which have now been adapted for patients with unsuccessful tyrosine kinase inhibitor treatment. In this review, we describe mechanisms of tyrosine kinase inhibitor resistance and the available strategies to overcoming resistance.

• Tuberculosis and Respiratory Diseases
• /
• v.70 no.6
• /
• pp.462-473
• /
• 2011

Background: Smoking is a risk factor for idiopathic pulmonary fibrosis (IPF), but the mechanism of the association remains obscure. There is evidence demonstrating that plasminogen activator inhibitor-1 (PAI-1) is involved in the progression of pulmonary fibrosis. This study was to determine whether the administration of small interfering RNA (siRNA) targeting PAI-1 or PAI-1 inhibitor to the cigarette smoking extract (CSE)-exposed rat alveolar type II epithelial cells (ATII cells) limits the epithelial-mesenchymal transition (EMT). Methods: ATII cells were isolated from lung of SD-rat using percoll gradient method and cultured with 5% CSE. The EMT was determined from the ATII cells by measuring the real-time RT PCR and western blotting after the PAI-1 siRNA transfection to the cells and after administration of tiplaxtinin, an inhibitor of PAI-1. The effect of PAI-1 inhibitor was also evaluated in the bleomycin-induced rats. Results: PAI-1 was overexpressed in the smoking exposed ATII cells and was directly associated with EMT. The EMT from the ATII cells was suppressed by PAI-1 siRNA transfection or administration of tiplaxtinin. Signaling pathways for EMT by smoking extract were through the phosphorylation of SMAD2 and ERK1/2, and finally Snail expression. Tiplaxtinin also suppressed the pulmonary fibrosis and PAI-1 expression in the bleomycin-induced rats. Conclusion: Our data shows that CSE induces rat ATII cells to undergo EMT by PAI-1 via SMAD2-ERK1/2-Snail activation. This suppression of EMT by PAI-1 siRNA transfection or PAI-1 inhibitor in primary type II alveolar epithelial cells might be involved in the attenuation of bleomycin-induced pulmonary fibrosis in rats.

• Tuberculosis and Respiratory Diseases
• /
• v.77 no.6
• /
• pp.271-273
• /
• 2014

Disease flare-up after discontinuing epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) has been considered as a critical issue in lung cancer patients who have experienced radiologic progression after showing initial durable response. This is a case of systemic nocardiosis that occurred after chronic steroid use for radionecrosis from stereotactic radiosurgery. It was initially thought as a disease flare-up after stopping EGFR-TKI.

• Journal of Microbiology and Biotechnology
• /
• v.6 no.6
• /
• pp.391-396
• /
• 1996

The Gram-negative marine bacterium Marinomonas vaga, which requires 0.5 M NaCl concentration for optimal growth, is slightly halophilic. The growth of M vaga was highly resistant to the proton conductor, carbonyl cyanide m-chlorophenylhydrazone (CCCP) under alkaline pH conditions (pH 8.5) but very sensitive to CCCP under acidic pH conditions (pH 6.5). These results suggest that the respiratory chain-linked NADH oxidase system of M. vaga may lead to generation of a $Na^{+}$ electrochemical gradient. In order to examine the existence of $Na^{+}$-stimulated NADH oxidase in M. vaga, membrane fractions were prepared by the osmotic lysis method. The membrane-bound NADH oxidase oxidized both NADH and deamino-NADH as substrates and required $Na^{+}$ for maximum activity. The maximum activity of NADH oxidase was obtained at about pH 8.5 in the presence of 0.2 M NaCl. The site of $Na^{+}$-dependent activation in the NADH oxidase system was at the NADH:quinone oxidoreductase segment. The NADH oxidase and NADH:quinone oxidoreductase were very sensitive to the respiratory chain inhibitor, 2-heptyl-4-hydroxyquinoline-N-oxide (HQNO) in the presence of 0.2 M NaCl but highly resistant to another respiratory inhibitor, rotenone. Based on these findings, we conclude that M. vaga possesses the $Na^{+}$-dependent NADH:quinone oxidoreductase that may function as an electrogenic $Na^{+}$ pump.

• Journal of Microbiology and Biotechnology
• /
• v.25 no.12
• /
• pp.2007-2010
• /
• 2015

A new chemical inhibitor against severe acute respiratory syndrome (SARS) coronavirus helicase, 7-ethyl-8-mercapto-3-methyl-3,7-dihydro-1H-purine-2,6-dione, was identified. We investigated the inhibitory effect of the compound by conducting colorimetry-based ATP hydrolysis assay and fluorescence resonance energy transfer-based double-stranded DNA unwinding assay. The compound suppressed both ATP hydrolysis and double-stranded DNA unwinding activities of helicase with IC₅₀ values of 8.66 ± 0.26 μM and 41.6 ± 2.3 μM, respectively. Moreover, we observed that the compound did not show cytotoxicity up to 80 μM concentration. Our results suggest that the compound might serve as a SARS coronavirus inhibitor.

• Tuberculosis and Respiratory Diseases
• /
• v.75 no.6
• /
• pp.236-237
• /
• 2013

Many attempts have been made to find genetic abnormalities inducing carcinogenesis after the development of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor targeting EGFR in lung cancer. New target therapies have been already commercialized and studied along with the recent discovery of gene rearrangement involved in the carcinogenic process of non-small cell lung cancer. This study aims to investigate anplastic lymphoma kinase, c-ros oncogene 1, and receptor tyrosine kinase, in particular.

• Applied Biological Chemistry
• /
• v.33 no.3
• /
• pp.264-267
• /
• 1990

Representative synthetic piericidin-like compounds, such as hydroxypyridine and hydroxyquinoline derivatives, which showed high inhibition activity against NADH-ubiquinone oxidoreductase on the respiratory chain revealed good fungicide activity. Especially, hydrolrypyridine ones showed high activity against rice blast (Pyricularia oryzae) and barley powdery mildew (Erysiphe graminis).