• Title/Summary/Keyword: RPE1

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Sulfasalazine attenuates tamoxifen-induced toxicity in human retinal pigment epithelial cells

  • Hwang, Narae;Chung, Su Wol
    • BMB Reports
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    • v.53 no.5
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    • pp.284-289
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    • 2020
  • Tamoxifen, a nonsteroidal estrogen receptor (ER) antagonist, is used routinely as a chemotherapeutic agent for ER-positive breast cancer. However, it is also causes side effects, including retinotoxicity. The retinal pigment epithelium (RPE) has been recognized as the primary target of tamoxifen-induced retinotoxicity. The RPE plays an essential physiological role in the normal functioning of the retina. Nonetheless, potential therapeutic agents to prevent tamoxifen-induced retinotoxicity in breast cancer patients have not been investigated. Here, we evaluated the action mechanisms of sulfasalazine against tamoxifen-induced RPE cell death. Tamoxifen induced reactive oxygen species (ROS)-mediated autophagic cell death and caspase-1-mediated pyroptosis in RPE cells. However, sulfasalazine reduced tamoxifen-induced total ROS and ROS-mediated autophagic RPE cell death. Also, mRNA levels of tamoxifen-induced pyroptosis-related genes, IL-1β, NLRP3, and procaspase-1, also decreased in the presence of sulfasalazine in RPE cells. Additionally, the mRNA levels of tamoxifen-induced AMD-related genes, such as complement factor I (CFI), complement factor H (CFH), apolipoprotein E (APOE), apolipoprotein J (APOJ), toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4), were downregulated in RPE cells. Together, these data provide novel insight into the therapeutic effects of sulfasalazine against tamoxifen-induced RPE cell death.

Gender Comparison of Ratings of Perceived Exertion (RPE) as a Predictor of Exercise Intensity in College Students (RPE에 의한 운동강도 예측인자의 남녀 대학생 비교)

  • Kim, Do-Yeon;Lee, Jeong-Ah
    • Journal of Life Science
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    • v.21 no.1
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    • pp.9-14
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    • 2011
  • Perceived exertion involves detection and interpretation of sensations arising from the body during physical exercise. Physiological variables such as heart rate and oxygen consumption positively correlate with ratings of perceived exertion (RPE). It is unknown whether the accuracy of predicting exercise intensity from RPE differs between men and women. Therefore, it was examined whether men or women could predict relative exercise intensity, determined by oxygen consumption, more accurately from RPE. Ten male and ten female young adult subjects aged 25.1${\pm}$3.52 yr volunteered to participate. RPE were determined by the Borg 15-category scale, and a standard Bruce treadmill protocol was used to perform graded exercise testing. There was no significant difference in slope means between males and females (p=0.501). No significant difference was observed when plotting rates of perceived exertion (RPE) vs. percentage of $VO_2$ max. The relative maximal oxygen consumptions ($VO_{2max,\;}_{rel}$) were 52.36${\pm}$7.35 ml/kg/min for males and 41.44${\pm}$6.71 ml/kg/min for females, respectively and there was a significantly high difference between the two groups in the relative $VO_{2max}$, as well as figures of 4.05${\pm}$0.36 l/min for males and 2.53${\pm}$0.39 l/min for females in the absolute $VO_{2max}$ in this study. There were no significant differences in slope, y-intercept, and standard error of estimate (SEE) between males and females. No significant difference with RPE according to exercise intensity was found between males and females. However, RPE was a useful predictor of exercise intensity in independent genders.

Wnt/β-Catenin Signaling Pathway Is Necessary for the Specification but Not the Maintenance of the Mouse Retinal Pigment Epithelium

  • Jong-Myeong Kim;Kwang Wook Min;You-Joung Kim;Ron Smits;Konrad Basler;Jin Woo Kim
    • Molecules and Cells
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    • v.46 no.7
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    • pp.441-450
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    • 2023
  • β-Catenin (Ctnnb1) has been shown to play critical roles in the development and maintenance of epithelial cells, including the retinal pigment epithelium (RPE). Ctnnb1 is not only a component of intercellular junctions in the epithelium, it also functions as a transcriptional regulator in the Wnt signaling pathway. To identify which of its functional modalities is critically involved in mouse RPE development and maintenance, we varied Ctnnb1 gene content and activity in mouse RPE lineage cells and tested their impacts on mouse eye development. We found that a Ctnnb1 double mutant (Ctnnb1dm), which exhibits impaired transcriptional activity, could not replace Ctnnb1 in the RPE, whereas Ctnnb1Y654E, which has reduced affinity for the junctions, could do so. Expression of the constitutively active Ctnnb1∆ex3 mutant also suppressed the development of RPE, instead facilitating a ciliary cell fate. However, the post-mitotic or mature RPE was insensitive to the loss, inactivation, or constitutive activation of Ctnnb1. Collectively, our results suggest that Ctnnb1 should be maintained within an optimal range to specify RPE through transcriptional regulation of Wnt target genes in the optic neuroepithelium.

Subretinal transplantation of putative retinal pigment epithelial cells derived from human embryonic stem cells in rat retinal degeneration model

  • Park, Un-Chul;Cho, Myung-Soo;Park, Jung-Hyun;Kim, Sang-Jin;Ku, Seung-Yup;Choi, Young-Min;Moon, Shin-Yong;Yu, Hyeong-Gon
    • Clinical and Experimental Reproductive Medicine
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    • v.38 no.4
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    • pp.216-221
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    • 2011
  • Objective: To differentiate the human embryonic stem cells (hESCs) into the retinal pigment epithelium (RPE) in the defined culture condition and determine its therapeutic potential for the treatment of retinal degenerative diseases. Methods: The embryoid bodies were formed from hESCs and attached on the matrigel coated culture dishes. The neural structures consisting neural precursors were selected and expanded to form rosette structures. The mechanically isolated neural rosettes were differentiated into pigmented cells in the media comprised of N2 and B27. Expression profiles of markers related to RPE development were analyzed by reverse transcription-polymerase chain reaction and immunostaining. Dissociated putative RPE cells ($10^5$ cells/5 ${\mu}L$) were transplanted into the subretinal space of rat retinal degeneration model induced by intravenous sodium iodate injection. Animals were sacrificed at 1, 2, and 4 weeks after transplantation, and immnohistochemistry study was performed to verify the survival of the transplanted cells. Results: The putative RPE cells derived from hESC showed characteristics of the human RPE cells morphologically and expressed molecular markers and associated with RPE fate. Grafted RPE cells were found to survive in the subretinal space up to 4 weeks after transplantation, and the expression of RPE markers was confirmed with immunohistochemistry. Conclusion: Transplanted RPE cells derived from hESC in the defined culture condition successfully survived and migrated within subretinal space of rat retinal degeneration model. These results support the feasibility of the hESC derived RPE cells for cell-based therapies for retinal degenerative disease.

A Study on Excitation Sequence Quantization in RPE Speech Coding (PVQ를 이용한 RPE 구동 시퀀스 양자화 연구)

  • 강상원
    • Proceedings of the Acoustical Society of Korea Conference
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    • 1995.06a
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    • pp.164-167
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    • 1995
  • RPE 음성부호화기에서 합성 필터로 인한 구동벡터 양자화잡음의 증폭효과를 분석하고 regular pulse 시퀀스의 양자화로 인한 성능감쇄를 줄이기 위해 pyramid vector 양자화방식을 도입하였다. 제안된 방식의 성능평가는 구동시퀀스 양자화를 위해 adaptive PCM을 이용하는 GSM 표준 RPE 방식과의 객관적 및 주관적 성능비교를 통해 수행하였다.T JDSMDQLRY 결과 제안된 방식은 대략 1dB의 SNR 및 segmental SNR 값 증가를 가져왔고, 또한 비공식 청취시험결과 명료도의 증가를 느낄 수 있었다.

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AMPK-induced mitochondrial biogenesis decelerates retinal pigment epithelial cell degeneration under nutrient starvation

  • Yujin Park;Yeeun Jeong;Sumin Son;Dong-Eun Kim
    • BMB Reports
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    • v.56 no.2
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    • pp.84-89
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    • 2023
  • The implications of nutrient starvation due to aging on the degeneration of the retinal pigment epithelium (RPE) is yet to be fully explored. We examined the involvement of AMPK activation in mitochondrial homeostasis and its relationship with the maintenance of a healthy mitochondrial population and epithelial characteristics of RPE cells under nutrient starvation. Nutrient starvation induced mitochondrial senescence, which led to the accumulation of reactive oxygen species (ROS) in RPE cells. As nutrient starvation persisted, RPE cells underwent pathological epithelial-mesenchymal transition (EMT) via the upregulation of TWIST1, a transcription regulator which is activated by ROS-induced NF-κB signaling. Enhanced activation of AMPK with metformin decelerated mitochondrial senescence and EMT progression through mitochondrial biogenesis, primed by activation of PGC1-α. Thus, by facilitating mitochondrial biogenesis, AMPK protects RPE cells from the loss of epithelial integrity due to the accumulation of ROS in senescent mitochondria under nutrient starvation.

Adhesion and Proliferation Behavior of Retinal Pigment Epithelial Cells on Hesperidin/PLGA Films (헤스페리딘/PLGA 필름에서 망막색소상피세포의 부착과 증식거동)

  • Lee, So Jin;Kang, Su Ji;Kim, Hye Yun;Lee, Jung Hwan;Kim, Eun Young;Kwon, Soon Yong;Chung, Jin Wha;Joo, Choun-Ki;Khang, Gilson
    • Polymer(Korea)
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    • v.38 no.1
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    • pp.24-30
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    • 2014
  • Retinal pigment epithelium (RPE) plays an important role in maintaining the visual function and the degeneration of the RPE causes several retinal degeneration disease. In order to fabricate the suitable carrier for RPE transplantation, the hybrid poly(lactide-co-glycolide) (PLGA) film with hesperidin was prepared. Hesperidin has an anti-inflammatory and antioxidant characteristics. ARPE-19 was seeded on hesperidin/PLGA film and then, cell proliferation was determined by the MTT assay, and cell adhesion and cell morphology were confirmed by SEM. Also, RT-PCR was performed to confirm the expression of the specific genes, and AEC immunohistochemical staining was performed to determine the expression of RPE65. As a result, we confirmed that attachment, proliferation and phenotype maintenance of RPE cells were more excellent on hesperidin/PLGA film than PLGA film, thereby we were able to confirm the potential applications of hesperidin/PLGA film as tissue engineering carrier for regeneration of retina.

Morphology and Mechanical Properties of Waste PVC Blends (I) -Morphology and Mechanical Properties of Waste PVC/PE Blends (폐 PVC계 고분자 블렌드의 구조 및 물성 연구(I) -폐 PVC/PE고분자 블렌드의 모폴로지 및 물성)

  • 박재찬;원종찬;최길영;이재흥;조성만;김명기
    • Polymer(Korea)
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    • v.26 no.1
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    • pp.37-44
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    • 2002
  • The polymer blends of waste polyvinyl chloride (RPVC) and waste polyethylene(RPE) were prepared by melt mixing, and their morphology and tensile properties were evaluated after the copolymers having an ethylene group in backbone and ester group in side position were added as comptatibilizers. The blend compositions were varied as follows ; RPVC/RPE 85/15 wt%, where RPVC formed a continuous phase : 50/50, mid composition : 15/85, RPE a continuous phase. The blends revealed a very low compatibility between component polymers because they showed domain sizes greater than $10\mu\textrm{m}$ over all compositions, especially the worst compatibility around mid composition. The blends showed higher compatibility when ethylene vinylacetate copolymer(EVA) and ethylene ethylacrylate-graft-methyl methacrylate copolymers(EEA-MMA) were added.

Re-expansion Pulmonary Edema in a patient with Secondary Spontaneous Pneumothorax Following Closed Thoracostomy: A Case Report (이차성 자연기흉 환자에게 폐쇄식 흉관삽입술로 인한 재팽창성 폐부종에 관한 증례보고)

  • Seon Woo Oh;Su Wan Kim
    • Journal of Medicine and Life Science
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    • v.18 no.3
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    • pp.61-65
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    • 2021
  • Although re-expansion pulmonary edema (RPE) is rare (incidence rate <1%), it is associated with a mortality rate of >20%; therefore, early diagnosis and treatment are important. We report a case of RPE following chest tube insertion in a patient with spontaneous pneumothorax. We have specifically focused on the mechanism underlying RPE and the possible etiology. An 82-year-old man with a history of chronic anemia, chronic obstructive pulmonary disease, diabetes mellitus, and hypertension was referred to the emergency department for management of recurrent right-sided pneumothorax. We performed emergency closed thoracostomy for suspected tension pneumothorax, which led to stabilization of the patient's vital signs; however, he coughed up frothy pink sputum accompanied by severe right-sided chest pain 30 min postoperatively. The patient showed new-onset right pulmonary consolidation on chest radiography, as well as desaturation, tachycardia, and tachypnea and was diagnosed with RPE. He was transferred to the intensive care unit for mechanical ventilation and supportive treatment using diuretics, ionotropic agents, and prophylactic antibiotics. RPE gradually resolved, and the patient was extubated 3 days after admission. He has not experienced recurrent pneumothorax or pulmonary disease for 4 months. We emphasize the importance of RPE prevention and that aggressive ventilator care and supportive treatment can effectively treat RPE following an accurate understanding of the underlying pathogenetic mechanisms and risk factors.

Differential Roles of Tubby Family Proteins in Ciliary Formation and Trafficking

  • Hong, Julie J.;Kim, Kyung Eun;Park, So Young;Bok, Jinwoong;Seo, Jeong Taeg;Moon, Seok Jun
    • Molecules and Cells
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    • v.44 no.8
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    • pp.591-601
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    • 2021
  • Cilia are highly specialized organelles that extend from the cell membrane and function as cellular signaling hubs. Thus, cilia formation and the trafficking of signaling molecules into cilia are essential cellular processes. TULP3 and Tubby (TUB) are members of the tubby-like protein (TULP) family that regulate the ciliary trafficking of G-protein coupled receptors, but the functions of the remaining TULPs (i.e., TULP1 and TULP2) remain unclear. Herein, we explore whether these four structurally similar TULPs share a molecular function in ciliary protein trafficking. We found that TULP3 and TUB, but not TULP1 or TULP2, can rescue the defective cilia formation observed in TULP3-knockout (KO) hTERT RPE-1 cells. TULP3 and TUB also fully rescue the defective ciliary localization of ARL13B, INPP5E, and GPR161 in TULP3 KO RPE-1 cells, while TULP1 and TULP2 only mediate partial rescues. Furthermore, loss of TULP3 results in abnormal IFT140 localization, which can be fully rescued by TUB and partially rescued by TULP1 and TULP2. TUB's capacity for binding IFT-A is essential for its role in cilia formation and ciliary protein trafficking in RPE-1 cells, whereas its capacity for PIP2 binding is required for proper cilia length and IFT140 localization. Finally, chimeric TULP1 containing the IFT-A binding domain of TULP3 fully rescues ciliary protein trafficking, but not cilia formation. Together, these two TULP domains play distinct roles in ciliary protein trafficking but are insufficient for cilia formation in RPE-1 cells. In addition, TULP1 and TULP2 play other unknown molecular roles that should be addressed in the future.