• BMB Reports
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• 제47권10호
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• pp.563-568
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• 2014

Human genome projects have enabled whole genome mapping and improved our understanding of the genes in humans. However, many unknown genes remain to be functionally characterized. In this study, we characterized human chromosome 4 open reading frame 34 gene (hC4orf34). hC4orf34 was highly conserved from invertebrate to mammalian cells and ubiquitously expressed in the organs of mice, including the heart and brain. Interestingly, hC4orf34 is a novel ER-resident, type I transmembrane protein. Mutant analysis showed that the transmembrane domain (TMD) of hC4orf34 was involved in ER retention. Overall, our results indicate that hC4orf34 is an ER-resident type I transmembrane protein, and might play a role in ER functions including $Ca^{2+}$ homeostasis and ER stress.

• 한국동물학회지
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• 제38권2호
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• pp.167-176
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• 1995

Glucose-regulated proteins (grp's), srp94 3nd grp78/BiP, are a group of stress proteins which are highly synthesized in cells exposed to a variety of stressful agents including tunicamycin 3nd Ca2+ ionophore. Grp78/BiP is hon to function as a molecular chaperone which regulates the folding and assembly of secretory or membrane proteins, but the biological function of grp941 remains to be elucidated. In this study, we have examined the intracellular distribution of grV's and the function of srp94. Grp's are resident in the endoplasmic reticulum (ERI 3nd a specific sequence (Lys-Asp-Glu-Leu) at their C-terminus is known to be responsible for their retention within the ER. However, it has been unclear whether upon disturbance of cellular Caa+ homeostasis by the Ca2+ ionophore, grp94 is retained within the ER or secreted into the medium. In this study, we showed that in the presence of C3a+ ionophore, grp94 and gif78/BiP are present in the cells, mainly within the ER. We have also investigated whether grp94 might function as a molecular chaperone. Here we showed that in the immunoglobulin (Ig)-secreting hvbridom3 cells, grp94 transientlY interacts with fully glycosylated Is heavy chain, suggesting that grpg94 may be involved in facilitating the folding and assembly of Ig heavy chains.

• 생명과학회지
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• 제25권4호
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• pp.473-480
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• 2015

진핵세포의 소포체는 분비를 담당하는 첫 번째 기관이다. 대부분의 분비단백질과 막 형성단백질은 소포체에서 세포질/핵으로 전달되는 신호전달에 의한 번역후수식에 의해서 소포체를 통해서 분비된다. 그 결과 완전하게 접 힘이 일어난 단백질만 세포 밖으로 분비된다. 소포체내에서 완전하게 접힘이 일어나지 않아 축적된 단백질은 세 포내스트레스(소포체스트레스)가 되어 unfolded protein response (UPR)시스템을 작동시킨다. UPR을 작동시키는 3종류의 소포체막단백질은 inositol requiring 1 (IRE1), PKR-like ER kinase (PERK), activating transcription factor 6 (ATF6)이 존재한다. 최근에 새로운 종류의 ATF6이 동정되었다. 이들은(Luman, OASIS, BBF2H7, CREBH, CREB4) 공통적으로 소포체막관통영역, 전사활성영역, bZIP영역을 가지며 특이조직과 세포내기관에서 기능을 가 진다. 현재로서는 OASIS family의 정확한 분자기전 설명은 어렵지만, 본 리뷰에서 이들 분자신호를 포괄적으로 소개할 것이다

• The Korean Journal of Physiology and Pharmacology
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• 제11권6호
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• pp.239-246
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• 2007

Expressions of endoplasmic reticulum stress response (ERSR) genes were examined during the neuronal differentiation of rat fetal cortical precursor cells (rCPC) and rat pheochromocytoma PC12 cells. When rCPC were differentiated into neuronal cells for 7 days, early stem cell marker, nest in, expression was decreased from day 4, and neuronal markers such as neurofilament-L, -M and Tuj1 were increased after day 4. In this condition, expressions of BIP, ATF6, and phosphorylated PERK as well as their down stream signaling molecules such as CHOP, ATF4, XBP1, GADD34, Nrf2 and $p58^{IPK}$ were significantly increased, suggesting the induction of ERSR during neuronal differentiation of rCPC. ERSR was also induced during the differentiation of PC12 cells for 9 days with NGF. Neurofilament-L transcript was time-dependently increased. Both mRNA and protein levels of Tuj1 were increased after the induction, and the significant increase in NeuN was observed at day 9. Similar to the expression patterns of neuronal markers, BIP/GRP78 and CHOP mRNAs were highly increased at day 9, and ATF4 mRNA was also increased from day 7. These results strongly suggest the induction and possible role of ERSR in neuronal differentiation process. Further study to identify targets responsible for neuronal induction will be necessary.

• 한국수정란이식학회지
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• 제32권4호
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• pp.287-295
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• 2017

Mitochondrial dysfunction is found in oocytes and transmitted to offspring due to maternal obesity. Treatment of obese mothers with endoplasmic reticulum (ER) stress inhibitors such as salubrinal (SAL) can reverse the mitochondrial dysfunction and result in normal embryonic development. Pig oocytes have also shown ER stress mostly in metaphase II stage. ER stress in oocytes may hinder the in vitro production of pig embryos. This study investigated the effect of ER stress inhibition by SAL treatment during in vitro maturation (IVM) of porcine oocytes at 1, 10, 50 and 100 nM concentrations. Firstly, we tested various concentrations of SAL. SAL at 10 nM showed higher (P < 0.05) developmental competence to the blastocyst stage (55.6%) after parthenogenesis (PA) than control (44.2%) while not different from other concentrations (49.2, 51.6, and 50.8% for 1, 50, and 100 nM, respectively). Secondly, we performed time-dependent treatment at 10 nM of SAL for IVM of oocytes. It revealed that treatment with SAL during 22 to 44 h of IVM significantly improved PA embryonic development to the blastocyst stage compared to control (40.5, 46.3, 51.7 and 60.2% for control, 0 to 22 h, 22 to 44 h and 0 to 44 h of IVM, respectively, P < 0.05). Glutathione (GSH) content is an indicator of cytoplasmic maturation of oocytes. Reactive oxygen species (ROS) have a harmful effect on developmental competence of oocytes. For this, we determined the intraoocyte levels of GSH and ROS after 44 h of IVM. It was found that SAL increased intraoocyte GSH level and also decreased ROS level (P < 0.05). Finally, we performed somatic cell nuclear transfer (SCNT) after treating oocytes with 10 nM SAL during IVM. SAL treatment significantly improved blastocyst formation of SCNT embryos compared to control (39.6% vs. 24.7%, P < 0.05). Our results indicate that treatment of pig oocytes with ER stress inhibitor SAL during IVM improves preimplantation development PA and cloned pig embryos by influencing cytoplasmic maturation in terms of increased GSH content and decreased ROS level in IVM pig oocytes.

• 생명과학회지
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• 제23권9호
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• pp.1104-1108
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• 2013

에틸렌 글리콜(ethylene glycol)은 자동차 부동액 주성분으로 우리 실생활에 널리 쓰이고 있다. 접근이 용이하고 달콤한 맛 때문에 자살목적이나 보관 및 사용 시 의도적으로 또는 실수로 인한 오용사고가 자주 발생한다. 에틸렌 글리콜은 그 자체로는 인체의 독성이 낮지만 생체에서 대사과정을 거치면서 독성이 높아진 유기산을 만들어 다양한 조직에서 광범위한 세포손상을 유발한다. 다양한 세포 스트레스가 소포체(ER) 샤페론과 소포체 스트레스 센서의 유전자 발현을 유도하는 것은 이미 알려져 있다. 본 연구에서는 rat 조직에서 소포체 샤페론과 소포체 스트레스 센서 유전자의 발현 조절이 에틸렌 글리콜에 의해 유도되고, 조직학적 변화도 H&E 염색 및 면역 형광염색에 의해 확인하였다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권7호
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• pp.2993-2999
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• 2014

Saccharina japonica is a family member of Phaeophyceae (brown macro-alga) and extensively cultivated in China, Japan and Korea. Here, the potential anti-cancer effect of n-hexane fraction of S. japonica was evaluated in SK-Hep1 human hepatocellular carcinoma cells. The N-hexane fraction reduced cell viability and increased the numbers of apoptotic cells in a both dose- and time-dependent manner. Apoptosis was activated by both caspase-dependent and independent pathways. The caspase-dependent cell death pathway is mediated by cell surface death receptors and activated caspase-8 amplified the apoptotic signal either through direct activation of downstream caspase-3 or pro-apoptotic proteins (Bad, Bax and Bak) subsequently leading to the release of cytochrome c. On the other hand, caspase-independent apoptosis appeared mediated by disruption of mitochondrial membrane potential and translocation of AIF to the nucleus where they induced chromatin condensation and/or large-scale DNA fragmentation. In addition, the n-hexane fraction induced endoplasmic reticulum (ER)-stress and cell cycle arrest. The results suggested that potential anti-cancer effects of n-hexane extract from S. japonica on SK-Hep1 cells.

• 한국생명과학회:학술대회논문집
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• 한국생명과학회 2008년도 제49회 학술심포지움 및 국제학술대회
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• pp.88.1-88.1
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• 2008

• 한국생명과학회:학술대회논문집
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• 한국생명과학회 2008년도 제49회 학술심포지움 및 국제학술대회
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• pp.88.2-88.2
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• 2008

• 한국발생생물학회지:발생과생식
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• 제22권4호
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• pp.403-403
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• 2018