• Applied Biological Chemistry
• /
• v.39 no.2
• /
• pp.104-111
• /
• 1996

We have isolated several proteinase inhibitor II genes pin2 from a Russet Burbank potato DNA library. One of these, pin2T was subcloned and a 1.8 kb Xbal/Nsil insert was sequenced. This fragment contained the complete Inhibitor II gene including 965 Up of flanking DNA upstream from the gene and 200 bp of flanking DNA downstream from the gene. The open reading frame encodes a protein that is similar to other reported proteinase Inhibitor II proteins. The DNA sequence of the 5' flanking region of pin2T from -714 to +1 is highly homologous (91% identity) with that of the previously isolated wound-inducible pin2K. There are, however, four small deletions in the pin2T promoter which are located at -221 to -200, -263 to -254, -523 to -426 and -759 to -708 relative to the transcription start site of the wound-inducible pin2K. Three of these deletions map to a portion of the promoter that controls the wound-inducibility of the proteinase inhibitor genes. Chimeric genes containing the promoter of the pin2T gene linked with the both CAT and GUS were constructed and transfered into tobacco plants. Analysis of these plants indicated that pin2T is not a wound-inducible gene but is expressed at low levels. Thus, wound-inducibility is lost with the concomitant natural deletion of three small regions of the promoter. Comparision of the sequences deleted in pin2T relative to the pin2K with Genebank sequences indicates that the deleted sequences contain a motif (consensus 5'-AGTAAA-3') that is found in many other wound-inducible genes but not easily found in the published promoter sequences of other plant genes. Nuclear proteins from unwounded and wounded potato leaves were bound to the proximal promoter region, downstream of the 5'-AGTAAA-3', of pin2T. The comparison of the pin2T gone with the pin2K gene indicates that the natural internal promoter deletions are likely responsible for loss of the wound-inducible phenotype in the pin2T gene.

• Proceedings of the Korean Society of Toxicology Conference
• /
• 2003.10b
• /
• pp.166-166
• /
• 2003

Cytochrome P-450 3A4 (CYP3A4) is major enzyme in human liver, the role of this is detoxification and metabolizing more than 50% clinical drugs in use. The transcription of CYP3A4 is regulated by the Pregnenolone X receptor (PXR),of which human form is Steroid and Xenobiotics receptor (SXR).(omitted)

• Journal of Applied Biological Chemistry
• /
• v.66
• /
• pp.165-170
• /
• 2023

Isolation of the culture broth of a marine-derived Acremonium sp. CNQ-049 guided by HPLC-UV yielded compound 1 (3-phenethyl-2-phenylquinazolin-4(3H)-one), and its inhibitory activities against monoamine oxidases (MAOs), cholinesterases (ChEs), and β-secretase 1 (BACE1) were evaluated. Compound 1 was an effective selective MAO-B inhibitor with an IC₅₀ value of 9.39 µM and a selectivity index (SI) value of 4.26 versus MAO-A. In addition, compound 1 showed a potent selective butyrylcholinesterase (BChE) inhibition with an IC₅₀ value of 7.99 µM and an SI value of 5.01 versus acetylcholinesterase (AChE). However, compound 1 showed weak inhibitions against MAO-A, AChE, and BACE1. The Ki value of compound 1 for MAO-B was 5.22±1.73 µM with competitive inhibition, and the Ki value of compound 1 for BChE was 3.00±1.81 µM with mixed-type inhibition. Inhibitions of MAO-B and BChE by compound 1 were recovered by dialysis experiments. These results suggest that compound 1 is a dual-functional reversible inhibitor of MAO-B and BChE, that can be used as a treatment agent for neurological disorders.

• Korean Journal of Clinical Pharmacy
• /
• v.20 no.3
• /
• pp.229-234
• /
• 2010

섬유근통 증후군은 만성 전신 통증을 나타내며 피곤, 두통, 우울증, 수면장애 등을 동반하는 질환이다. 주로 30-50대의 여성에게서 많이 나타나며 미국에서 2-4%, 한국에서 2%의 발병률을 보이고 있다. 정확한 원인과 기전이 밝혀져 있지 않아서 진단과 치료에 많은 논란과 어려움이 있다. 현재는 증상치료에 목표를 두고 삼환계항우울약을 많이 사용하고 있으나 심각한 부작용의 문제가 있다. 이러한 문제 때문에 최근에는 selective serotonin reuptake inhibitor (SSRI) 또는 serotonin-norepinephrine reuptake inhibitor (SNRI)를 빈번히 사용하고 있다. 본 연구는 SNRI의 하나인 milnacipran의 섬유근통 증후군 치료에 대한 효능 및 안정성을 알아보기 위해, MEDLINE에 등재된 논문을 기한없이 milnacipran과 fibromyalgia로 검색하여 무작위 배정 및 이중맹검 임상연구자료들을 선별하였다. 선별된 6개의 임상연구 결과, milnacipran를 사용했을 때 일관된 효능성과 안정성이 관찰되었고 섬유근통증후군 치료와 그에 수반되는 여러증상에 효과적인 것으로 나타났다.

• Korean Journal of Microbiology
• /
• v.28 no.4
• /
• pp.297-303
• /
• 1990

Secretion of Serratia marcescens nuclease by E. coli harboring pNUC4 was investigated. 29.2, 54.2 and 16.6% of total nuclease were observed in culture medium, periplasm, and cytoplasm of E. coli, respectively. To investigate the secretion mechanism of Serratia nuclease by E. coli, secretion kinetics of nuclease was examined in the presences of sodium azide, and energy metabolism inhibitor; procaine, an exoprotein processing inhibitor; and chloramphenicol, a protein synthesis inhibitor. In the presence of sodium azide, periplasmic unclease was gradually decreased and the extracellular nyclease was linearly increased according to the incubation time. Similar results were obtained in presences of procaine and chloramphenicol. From these results, we concluded that two transport processes are involved in nuclease secretion: secretion of nuclease through the inner membrane is occurred by an energy-dependent process and probably requiring precusor processing: secretion of nuclease through outer membrane does not require energy, de novo protein synthesis, and precursor processing.

• Journal of Yeungnam Medical Science
• /
• v.16 no.1
• /
• pp.69-75
• /
• 1999

Imidapril(Tanatril$^{(R)}$), a newly developed ACE inhibitor, has been used to treat hypertension and congestive heart failure. This study was designed to assess the antihypertensive effect and safety of Imidapril(Tanatril$^{(R)}$) in patients with essential hypertension. 5-10mg of imidapril(Tanatril$^{(R)}$) was administered once a day in 30 patients with essential hypertension and followed up for 8 weeks. We tested the drug's effectiveness, safety, and the incidence of imidapril induced dry coughs. After 8 weeks of treatment with imidapril, 76.2%(16/21) of patients showed lowered blood pressure and 47.6% showed normal blood pressure. The overall incidence of adverse effects was 33.3%(7/21), and among these adverse effects, dry cough was shown in only 9.5%. Thus, we concluded that imidapril(Tanatril$^{(R)}$) is as safe and effective as other ACE inhibitors, especially with imidapril showing very little incidence of dry cough compared to other ACE inhibitors.

• Biomolecules & Therapeutics
• /
• v.29 no.5
• /
• pp.562-570
• /
• 2021

Topoisomerase IIα has been a representative anti-cancer target for decades thanks to its functional necessity in highly proliferative cancer cells. As type of topoisomerase IIα targeting drugs, topoisomerase II poisons are frequently in clinical usage. However, topoisomerase II poisons result in crucial consequences resulted from mechanistically induced DNA toxicity. For this reason, it is needed to develop catalytic inhibitors of topoisomerase IIα through the alternative mechanism of enzymatic regulation. As a catalytic inhibitor of topoisomerase IIα, AK-I-191 was previously reported for its enzyme inhibitory activity. In this study, we clarified the mechanism of AK-I-191 and conducted various types of spectroscopic and biological evaluations for deeper understanding of its mechanism of action. Conclusively, AK-I-191 represented potent topoisomerase IIα inhibitory activity through binding to minor groove of DNA double helix and showed synergistic effects with tamoxifen in antiproliferative activity.

• The Korean Journal of Physiology and Pharmacology
• /
• v.22 no.2
• /
• pp.135-143
• /
• 2018

Tumor necrosis $factor-{\alpha}$ ($TNF{\alpha}$) and the angiotensin system are involved in inflammatory diseases and may contribute to acute kidney injury. We investigated the mechanisms by which $TNF{\alpha}$-converting enzyme (TACE) contributes to lipopolysaccharide (LPS)-induced renal inflammation and the effect of TACE inhibitor treatment on LPS-induced cellular injury in human renal proximal tubule epithelial (HK-2) cells. Mice were treated with LPS (10 mg/kg, i.p.) and HK-2 cells were cultured with or without LPS ($10{\mu}g/ml$) in the presence or absence of a type 1 TACE inhibitor ($1{\mu}M$) or type 2 TACE inhibitor ($10{\mu}M$). LPS treatment induced increased serum creatinine, $TNF{\alpha}$, and urinary neutrophil gelatinase-associated lipocalin. Angiotensin II type 1 receptor, mitogen activated protein kinase (MAPK), and TACE increased, while angiotensin-converting enzyme-2 (ACE2) expression decreased in LPS-induced acute kidney injury and LPS-treated HK-2 cells. LPS induced reactive oxygen species and the down-regulation of ACE2, and these responses were prevented by TACE inhibitors in HK-2 cells. TACE inhibitors increased cell viability in LPS-treated HK-2 cells and attenuated oxidative stress and inflammatory cytokines. Our findings indicate that LPS activates renin angiotensin system components via the activation of TACE. Furthermore, inhibitors of TACE are potential therapeutic agents for kidney injury.

• Bulletin of the Korean Chemical Society
• /
• v.34 no.4
• /
• pp.1286-1289
• /
• 2013

• Journal of Microbiology and Biotechnology
• /
• v.2 no.3
• /
• pp.220-225
• /
• 1992

Chemotaxonomic and numerical identification were carried out for an isolate of Streptomyces strain SMF13 producing thiol protease inhibitor. Fifty taxonomic unit characters were tested and the data were analyzed numerically using the TAXON program. The isolate SMF13 was identified to be a member of the cluster 5 of Streptomyces and best matched to Streptomyces omiyaensis which is a synonym of Streptomyces exfoliatus. Therefore. it was concluded that the isolate was identified to be a strain of Streptomyces exfoliatus.