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인동덩굴로부터 분리된 Cynaroside이 Doxorubicin으로 유도된 인간 근위세뇨관 HK-2 세포의 괴사에 미치는 저해 효과
노종현,정호경,이무진,장지훈,심미옥,정자균,정다은,안병관,조현우,Nho, Jong Hyun,Jung, Ho Kyung,Lee, Mu Jin,Jang, Ji Hun,Sim, Mi Ok,Jung, Ja Kyun,Jung, Da Eun,An, Byeong Kwan,Cho, Hyun Woo 한국약용작물학회 2017 한국약용작물학회지 Vol.25 No.5
Background: Cynaroside is a flavone, a flavonoid-like compound, known by different names (luteoloside and cinaroside). It is commonly found in Lonicera japonica Thunb., Chrysanthemum moriflium, and Angelica keiskei. The process of cell death has been classified as necrosis and apoptosis. Necrosis refers to unregulated cell death induced by a chemotherapeutic agent. Doxorubicin is an anthracycline anti-cancer drug used to treat acute leukemia, cancer, and lymphoma. However, it induces nephrotoxicity including tubular damage. Therefore, we investigated the protective effect of cynaroside against doxorubicin-induced necrosis in HK-2 cells. Methods and Results: To confirm the beneficial effect of cynaroside on doxorubicin-induced necrosis, HK-2 cells, a human proximal tubule epithelial cell line were treated with $10{\mu}M$ doxorubicin and $80{\mu}M$ cynaroside. Doxorubicin treatment resulted in increased DNA fragmentation, caspase-3 activity and mitochondria hyperactivation during cell necrosis. However, pretreatment with $80{\mu}M$ cynaroside attenuated DNA fragmentation, caspase-3 activity and mitochondria hyperactivation induced by $10{\mu}M$ doxorubicin in HK-2 cells. Conclusions: These results indicated that pretreatment with cynaroside ameliorated doxorubicin-induced necrosis in HK-2 cells. Therefore, cynaroside be used as a therapeutic agent for improving doxorubicin-induced nephrotoxicity. However, further studies are required to evaluated the toxicity of cynaroside treatment in animals and to determine its protective effect against doxorubicin-induced nephrotoxicity in an animal model.
Alu-Derived Alternative Splicing Events Specific to Macaca Lineages in CTSF Gene
Lee, Ja-Rang,Park, Sang-Je,Kim, Young-Hyun,Choe, Se-Hee,Cho, Hyeon-Mu,Lee, Sang-Rae,Kim, Sun-Uk,Kim, Ji-Su,Sim, Bo-Woong,Song, Bong-Seok,Jeong, Kang-Jin,Lee, Youngjeon,Jin, Yeung Bae,Kang, Philyong,Hu Korean Society for Molecular and Cellular Biology 2017 Molecules and cells Vol.40 No.2
Cathepsin F, which is encoded by CTSF, is a cysteine proteinase ubiquitously expressed in several tissues. In a previous study, novel transcripts of the CTSF gene were identified in the crab-eating monkey deriving from the integration of an Alu element-AluYRa1. The occurrence of AluYRa1-derived alternative transcripts and the mechanism of exonization events in the CTSF gene of human, rhesus monkey, and crabeating monkey were investigated using PCR and reverse transcription PCR on the genomic DNA and cDNA isolated from several tissues. Results demonstrated that AluYRa1 was only integrated into the genome of Macaca species and this lineage-specific integration led to exonization events by producing a conserved 3' splice site. Six transcript variants (V1-V6) were generated by alternative splicing (AS) events, including intron retention and alternative 5' splice sites in the 5' and 3' flanking regions of CTSF_AluYRa1. Among them, V3-V5 transcripts were ubiquitously expressed in all tissues of rhesus monkey and crab-eating monkey, whereas AluYRa1-exonized V1 was dominantly expressed in the testis of the crab-eating monkey, and V2 was only expressed in the testis of the two monkeys. These five transcript variants also had different amino acid sequences in the C-terminal region of CTSF, as compared to reference sequences. Thus, species-specific Alu-derived exonization by lineage-specific integration of Alu elements and AS events seems to have played an important role during primate evolution by producing transcript variants and gene diversification.
Lee, Ja-Rang,Kim, Young-Hyun,Park, Sang-Je,Choe, Se-Hee,Cho, Hyeon-Mu,Lee, Sang-Rae,Kim, Sun-Uk,Kim, Ji-Su,Sim, Bo-Woong,Song, Bong-Seok,Jeong, Kang-Jin,Lee, Youngjeon,Jin, Yeung Bae,Kang, Philyong,Hu Hindawi Publishing Corporation 2016 International journal of genomics Vol.2016 No.-
<P><I>TSEN54</I> encodes a subunit of the tRNA-splicing endonuclease complex, which catalyzes the identification and cleavage of introns from precursor tRNAs. Previously, we identified an<I> AluSx</I>-derived alternative transcript in<I> TSEN54</I> of cynomolgus monkey. Reverse transcription-polymerase chain reaction (RT-PCR) amplification and<I> TSEN54</I> sequence analysis of primate and human samples identified five novel alternative transcripts, including the<I> AluSx</I> exonized transcript. Additionally, we performed comparative expression analysis via RT-qPCR in various cynomolgus, rhesus monkey, and human tissues. RT-qPCR amplification revealed differential expression patterns. Furthermore, genomic PCR amplification and sequencing of primate and human DNA samples revealed that<I> AluSx</I> elements were integrated in human and all of the primate samples tested. Intriguingly, in langur genomic DNA, an additional<I> AluY</I> element was inserted into<I> AluSx</I> of intron eight of<I> TSEN54</I>. The new<I> AluY</I> element showed polymorphic insertion. Using standardized nomenclature for<I> Alu</I> repeats, the polymorphic<I> AluY</I> of the langur<I> TSEN54</I> was designated as being of the<I> AluYl17</I> subfamily. Our results suggest that integration of the<I> AluSx</I> element in<I> TSEN54</I> contributed to diversity in transcripts and induced lineage- or species-specific evolutionary events such as alternative splicing and polymorphic insertion during primate evolution.</P>
프로스타글란딘 유도체의 합성과 그의 생물학적 활성에 관한 연구 2. 위궤양과 위산분비에 대한 프로스타글란딘 유도체의 효과
조태순(Tai Soon Cho),이선미(Sun Mee Lee),함원훈(Won Hun Ham),이병무(Byung Mu Lee),김경례(Kyoung Rae Kim),지상철(Sang Cheol Chi),고준일(Jun Ill Ko),박인(In Park),오창영(Chang Young Oh),박호군(Ho Koon Park),김형자(Hyoung Ja Kim),이향우(H 한국응용약물학회 1995 Biomolecules & Therapeutics(구 응용약물학회지) Vol.3 No.1
The antiulcer effects of newly synthesized prostaglandin derivatives were investigated in various experimental ulcer models and on gastric secretion in rats. HK-3 and HK-4, PGE₂ derivatives, prevented the formation of acute gastric ulcer induced by ethanol or aspirin in pylorus-ligated rats. The ulcer formation was moderately inhibited by HK-1 and HK-2, PGF_(2α) derivatives, and aggravated by SK-1, SK-2 and SK-3, PGF_(2α) derivatives. HK-3 and HK-4 reduced the volume, acid output and pepsin output of gastric juice in pylorus-ligated rats. The gastric perfusion with physiologic saline(pH 6.0) showed relatively constant acid secretion and indomethacin increased the acid secretion. The acid secretion was markedly decreased by PGE₂ but PGF_(2α) caused little change. Prostaglandin derivatives, especially HK-3 and HK-4, significantly inhibited the acid secretion induced by indomethacin. The results show that, PGE₂ derivatives, HK-3 and HK-4, inhibit acid secretion and also have protective effects on gastric ulceration induced by ethanol or aspirin.