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기니 픽 회장 운동 기능에 미치는 phosphodiesterase 4형 및 5형 억제제의 효과
박효진,최성우,임정현,이상인,박인서 대한소화기학회 2002 대한소화기학회 춘계학술대회 Vol.2002 No.-
<배경 및 목적> 세포내 cAMP 또는 cGMP는 각각 adenylyl cylase 및 guanylate cyclase의 활성화에 반응하여 생성되며 phosphodiesterase (PDE)는 cAMP 및 cGMP의 대사에 관여하는 효소이다. 저자 등은 4형 및 5형 PDE 억제제가 기니 픽 회장 연동 및 근 수축에 미치는 영향을 알아보고자 본 연구를 시행하였다. <방법> 약 400 그램정도되는 수컷 기니 픽 회장을 채취하여 4형 PDE 억제제인 rol
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박효진,박재영,김진우,양슬기,정재민,김민지,박정준,구덕본 한국발생생물학회 2017 발생과 생식 Vol.21 No.4
In the present study, we investigated the role of binding immunoglobulin protein/glucose-regulated protein, 78-kDa (BIP/GRP78)-regulated endoplasmic reticulum (ER)-stress on meiotic maturation and cumulus cells expansion in porcine cumulus-oocyte complexes (COCs). Previously, it has been demonstrated that unfolded protein response (UPR)-related genes, such as molecules involved in ER-stress defense mechanisms, were expressed in matured oocytes and cumulus cells during in vitro maturation (IVM) of porcine oocytes. However, BIP/GRP78-mediated regulation of ER stress in porcine oocytes has not been reported. Firstly, we observed the effects of knockdown of BIP/GRP78 (an UPR initiation marker) using porcine-specific siRNAs (#909, #693, and #1570) on oocyte maturation. Among all siRNAs, siRNA #693 significantly re-duced the protein levels of UPR marker proteins (BIP/GRP78, ATF4, and P90ATF6) in porcine COCs observed by Western blotting and immunofluorescence analysis. We also observed that the reduction of BIP/GRP78 levels by siRNA#693 signifi-cantly inhibited the meiotic maturation of oocytes (siRNA #693: 32.5±10.1% vs control: 77.8±5.3%). In addition, we also checked the effect of ER-stress inhibitors, tauroursodeoxycholic acid (TUDCA, 200 μM) and melatonin (0.1 μM), in BIP/ GRP78-knockdown oocytes. TUDCA and melatonin treatment could restore the expression levels of ER-stress marker pro-teins (BIP/GRP78, p-eIF2α, eIF2α, ATF4, and P90ATF6) in siRNA #693-transfected matured COCs. In conclusion, these re-sults demonstrated that BIP/GRP78-mediated regulation of UPR signaling and ER stress plays an important role in in vitro maturation of porcine oocytes.
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박효진,최지하,김주희,윤진숙,최양지,최윤희,국경훈 연세대학교의과대학 2017 Yonsei medical journal Vol.58 No.6
Purpose: This study was conducted to identify and to functionally characterize genetic variants in ST3GAL5 and ST8SIA1 in Koreanpatients with thyroid-associated ophthalmopathy (TAO). Materials and Methods: Genetic analyses were conducted using DNA samples from TAO patients (n=50) and healthy subjects (n=48) to identify TAO-specific genetic variants of ST3GAL5 or ST8SIA1. The effect of each genetic variant on the transcription or expression of these genes was examined. Additionally, correlations between functional haplotypes of ST3GAL5 or ST8SIA1 and clinical characteristics of the patients were investigated. Results: Six promoter variants and one nonsynonymous variant of ST3GAL5 were identified, and four major promoter haplotypes were assembled. Additionally, three promoter variants and two major haplotypes of ST8SIA1 were identified. All ST3GAL5 and ST8SIA1 variants identified in TAO patients were also found in healthy controls. Promoter activity was significantly decreased in three promoter haplotypes of ST3GAL5 and increased in one promoter haplotype of ST8SIA1. Transcription factors activating protein-1, NKX3.1, and specificity protein 1 were revealed as having roles in transcriptional regulation of these haplotypes. The nonsynonymousvariant of ST3GAL5, H104R, did not alter the expression of ST3GAL5. While no differences in clinical characteristics were detected in patients possessing the functional promoter haplotypes of ST3GAL5, exophthalmic values were significantly lower in patients with the ST8SIA1 haplotype, which showed a significant increase in promoter activity. Conclusion: These results from genotype-phenotype analysis might suggest a possible link between the ST8SIA1 functional promoterhaplotype and the clinical severity of TAO. However, further studies with larger sample sizes are warranted.
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