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Tae Chul Moon,Chang Seob Seo,Kyungmi Haa,Jin Cheul Kim,Nam Kyung Hwang,Tae Gyun Hong,Jee Hyeun Kim,Do Hun Kim1,손종근,장현욱 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.5
Meso-dihydroguaiaretic acid (MDGA) is a medicinal herbal product isolated from the aerial parts of Saururus chinensis that inhibits the cyclooxygenase-2 (COX-2)-dependent phase of prostaglandin D2 (PGD2) generation in bone marrow-derived mast cells (BMMC) (IC50 9.8 μM). However, this compound did not inhibit COX-2 protein expression in BMMC at concentrations up to 30 μM, indicating that MDGA directly inhibits COX-2 activity. In addition, this compound consistently inhibited the production of leukotriene C4 (IC50 1.3 μM). These results demonstrate that MDGA inhibits both COX-2 and 5-lipoxygenase. Furthermore, this compound strongly inhibited the degranulation reaction in BMMC (IC50 11.4 μM). Therefore, this compound might provide a basis for novel anti-inflammatory drug development.
Distinct Z-DNA binding mode of a PKR-like protein kinase containing a Z-DNA binding domain (PKZ)
Kim, Doyoun,Hur, Jeonghwan,Park, Kwangsoo,Bae, Sangsu,Shin, Donghyuk,Ha, Sung Chul,Hwang, Hye-Yeon,Hohng, Sungchul,Lee, Joon-Hwa,Lee, Sangho,Kim, Yang-Gyun,Kim, Kyeong Kyu Oxford University Press 2014 Nucleic acids research Vol.42 No.9
<P>Double-stranded ribonucleic acid-activated protein kinase (PKR) downregulates translation as a defense mechanism against viral infection. In fish species, PKZ, a PKR-like protein kinase containing left-handed deoxyribonucleic acid (Z-DNA) binding domains, performs a similar role in the antiviral response. To understand the role of PKZ in Z-DNA recognition and innate immune response, we performed structural and functional studies of the Z-DNA binding domain (Zα) of PKZ from <I>Carassius auratus</I> (caZα<SUB>PKZ</SUB>). The 1.7-Å resolution crystal structure of caZα<SUB>PKZ</SUB>:Z-DNA revealed that caZα<SUB>PKZ</SUB> shares the overall fold with other Zα, but has discrete structural features that differentiate its DNA binding mode from others. Functional analyses of caZα<SUB>PKZ</SUB> and its mutants revealed that caZα<SUB>PKZ</SUB> mediates the fastest B-to-Z transition of DNA among Zα, and the minimal interaction for Z-DNA recognition is mediated by three backbone phosphates and six residues of caZα<SUB>PKZ</SUB>. Structure-based mutagenesis and B-to-Z transition assays confirmed that Lys56 located in the β-wing contributes to its fast B-to-Z transition kinetics. Investigation of the DNA binding kinetics of caZα<SUB>PKZ</SUB> further revealed that the B-to-Z transition rate is positively correlated with the association rate constant. Taking these results together, we conclude that the positive charge in the β-wing largely affects fast B-to-Z transition activity by enhancing the DNA binding rate.</P>
Leptin induces CREB-dependent aromatase activation through COX-2 expression in breast cancer cells
Kim, Hyung Gyun,Jin, Sun Woo,Kim, Yong An,Khanal, Tilak,Lee, Gi Ho,Kim, Se Jong,Rhee, Sang Dal,Chung, Young Chul,Hwang, Young Jung,Jeong, Tae Cheon,Jeong, Hye Gwang Elsevier 2017 Food and Chemical Toxicology Vol. No.
<P><B>Abstract</B></P> <P>Leptin plays a key role in the control of adipocyte formation, as well as in the associated regulation of energy intake and expenditure. The goal of this study was to determine if leptin-induced aromatase enhances estrogen production and induces tumor cell growth stimulation. To this end, breast cancer cells were incubated with leptin in the absence or presence of inhibitor pretreatment, and changes in aromatase and cyclooxygenase-2 (COX-2) expression were evaluated at the mRNA and protein levels. Transient transfection assays were performed to examine the aromatase and COX-2 gene promoter activities and immunoblot analysis was used to examine protein expression. Leptin induced aromatase expression, estradiol production, and promoter activity in breast cancer cells. Protein levels of phospho-STAT3, PKA, Akt, ERK, and JNK were increased by leptin. Leptin also significantly increased cAMP levels, cAMP response element (CRE) activation, and CREB phosphorylation. In addition, leptin induced COX-2 expression, promoter activity, and increased the production of prostaglandin E<SUB>2</SUB>. Finally, a COX-2 inhibitor and aromatase inhibitor suppressed leptin-induced cell proliferation in MCF-7 breast cancer cells. Together, our data show that leptin increased aromatase expression in breast cancer cells, which was correlated with COX-2 upregulation, mediated through CRE activation and cooperation among multiple signaling pathways.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Leptin increases aromatase expression and promoter activity in breast cancer cells. </LI> <LI> Leptin induces the intracellular levels of cAMP and the phosphorylation of PKA/CREB in MCF-7 cells. </LI> <LI> Leptin increases COX-2 expression and PGE<SUB>2</SUB> production in MCF-7 cells. </LI> <LI> Up-regulation of aromatase by leptin induces breast cancer cell proliferation. </LI> </UL> </P>
Kim, Hyun-Min,Kim, Hyun-Min,Lee, Min-Jung,Cho, Min-Gi,Kang, Deok,Kim, Yu-Kyung,Kim, Changmin,Kang, Do-Hyun,Jeong, Si-Hwa,Ahn, Ik-Gyun,Hwang, Jun-Hyeok,Kim, Jae-Hyun,Lee, Hyun-Jin,Jang, Jun-Yeong,Park, Cellmed Orthocellular Medicine and Pharmaceutical 2018 셀메드 (CellMed) Vol.8 No.1
Pharmacopuncture, or herbal acupuncture, is a new form of therapy derived from combinations of two traditional therapeutic methods, herbal medicine and acupuncture therapy. To compare the efficacy between loratadine-pharmacopuncture (LP) and loratadine-oral administration (LO), the effect of loratadine was investigated in murine models. Anti-anaphylactic effects of loratadine treatments were investigated in compound 48/80-induced systemic anaphylactic reaction and passive cutaneous anaphylaxis (PCA). LP treatment significantly inhibited the compound 48/80-induced systemic anaphylactic reaction and PCA. The effect between LP and LO were on a similar level. These results indicate that LP can be used as an alternative method for LO in case of emergency.