• Molecules and Cells
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• v.43 no.8
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• pp.671-685
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• 2020

The regulator of calcineurin (RCAN) was first reported as a novel gene called DSCR1, encoded in a region termed the Down syndrome critical region (DSCR) of human chromosome 21. Genome sequence comparisons across species using bioinformatics revealed three members of the RCAN gene family, RCAN1, RCAN2, and RCAN3, present in most jawed vertebrates, with one member observed in most invertebrates and fungi. RCAN is most highly expressed in brain and striated muscles, but expression has been reported in many other tissues, as well, including the heart and kidneys. Expression levels of RCAN homologs are responsive to external stressors such as reactive oxygen species, Ca²⁺, amyloid β, and hormonal changes and upregulated in pathological conditions, including Alzheimer's disease, cardiac hypertrophy, diabetes, and degenerative neuropathy. RCAN binding to calcineurin, a Ca²⁺/calmodulin-dependent phosphatase, inhibits calcineurin activity, thereby regulating different physiological events via dephosphorylation of important substrates. Novel functions of RCANs have recently emerged, indicating involvement in mitochondria homeostasis, RNA binding, circadian rhythms, obesity, and thermogenesis, some of which are calcineurin-independent. These developments suggest that besides significant contributions to DS pathologies and calcineurin regulation, RCAN is an important participant across physiological systems, suggesting it as a favorable therapeutic target.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.1
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• pp.81-88
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• 2020

Regulator of calcineurin 1 (RCAN1) can be induced by an intracellular calcium increase and oxidative stress, which are characteristic features of temporal lobe epilepsy. Thus, we investigated the spatiotemporal expression and cellular localization of RCAN1 protein and mRNA in the mouse hippocampus after pilocarpine-induced status epilepticus (SE). Male C57BL/6 mice were given pilocarpine hydrochloride (280 mg/kg, i.p.) and allowed to develop 2 h of SE. Then the animals were given diazepam (10 mg/kg, i.p.) to stop the seizures and sacrificed at 1, 3, 7, 14, or 28 day after SE. Cresyl violet staining showed that pilocarpine-induced SE resulted in cell death in the CA1 and CA3 subfields of the hippocampus from 3 day after SE. RCAN1 immunoreactivity showed that RCAN1 was mainly expressed in neurons in the shammanipulated hippocampi. At 1 day after SE, RCAN1 expression became detected in hippocampal neuropils. However, RCAN1 signals were markedly enhanced in cells with stellate morphology at 3 and 7 day after SE, which were confirmed to be reactive astrocytes, but not microglia by double immunofluorescence. In addition, realtime reverse transcriptase-polymerase chain reaction showed a significant upregulation of RCAN1 isoform 4 (RCAN1-4) mRNA in the SE-induced hippocampi. Finally, in situ hybridization with immunohistochemistry revealed astrocytic expression of RCAN1-4 after SE. These results demonstrate astrocytic upregulation of RCAN1 and RCAN1-4 in the mouse hippocampus in the acute and subacute phases of epileptogenesis, providing foundational information for the potential role of RCAN1 in reactive astrocytes during epileptogenesis.

• Molecules and Cells
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• v.37 no.11
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• pp.785-794
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• 2014

Mitophagy, a cellular process that selectively targets dysfunctional mitochondria for degradation, is currently a hot topic in research into the pathogenesis and treatment of many human diseases. Considering that hypoxia causes mitochondrial dysfunction, which results in cell death, we speculated that selective activation of mitophagy might promote cell survival under hypoxic conditions. In the present study, we introduced the Regulator of calcineurin 1-1L (Rcan1-1L) to initiate the mitophagy pathway and aimed to evaluate the effect of Rcan1-1L-induced mitophagy on cell survival under hypoxic conditions. Recombinant adenovirus vectors carrying Rcan1-1L were transfected into human umbilical vein endothelial cells and human adult cardiac myocytes. Using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MTT assay and Trypan blue exclusion assay, Rcan1-1L overexpression was found to markedly reverse cell growth inhibition induced by hypoxia. Additionally, Rcan1-1L overexpression inhibited cell apoptosis under hypoxic conditions, as detected by annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) apoptosis assay. Meanwhile, the mitochondria-mediated cell apoptotic pathway was inhibited by Rcan1-1L. In contrast, knockdown of Rcan1-1L accelerated hypoxia-induced cell apoptosis. Moreover, Rcan1-1L overexpression significantly reduced mitochondrial mass, decreased depolarized mitochondria, and downregulated ATP and reactive oxygen species production. We further delineated that the loss of mitochondrial mass was due to the activation of mitophagy induced by Rcan1-1L. Rcan1-1L overexpression activated autophagy flux and promoted translocation of the specific mitophagy receptor Parkin into mitochondria from the cytosol, whereas inhibition of autophagy flux resulted in the accumulation of Parkin-loaded mitochondria. Finally, we demonstrated that mitochondrial 1permeability transition pore opening was significantly increased by Rcan1-1L overexpression, which suggested that Rcan1-1L might evoke mitophagy through regulating mitochondrial permeability transition pores. Taken together, we provide evidence that Rcan1-1L overexpression induces mitophagy, which in turn contributes to cell survival under hypoxic conditions, revealing for the first time that Rcan1-1L-induced mitophagy may be used for cardioprotection.

• Proceedings of the Korean Society of Broadcast Engineers Conference
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• 2022.11a
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• pp.85-87
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• 2022

최근 CCTV 출입 기록, 휴대폰 보안, 스마트 매장 등에서 얼굴 인식을 통해 개인을 식별하는 기술이 널리 사용되고 있다. 카메라의 각도, 조명, 사람의 움직임 등 얼굴 인식에 많은 외부 환경이 영향을 미치고 있지만 그중에서도 실제 영상에서 얼굴이 차지하는 영역이 작아 저해상도 얼굴 인식에 어려움을 겪고 있다. 이러한 문제점을 해결하고자 본 논문에서는 이미지 해상도가 얼굴 인식에 끼치는 영향을 알아보고 이미지 초해상화를 통해 얼굴 인식 성능을 개선하고자 한다. 쌍선형, 양3차 회선 보간법과 딥러닝 기반의 이미지 초해상화 모델인 RCAN을 이용하여 업스케일링한 데이터셋에 대해 학습한 ArcFace를 통해 얼굴 검증 평가를 진행하였다. 고해상도 이미지는 얼굴 인식 성능을 향상시키며, RCAN을 사용한 이미지 초해상화가 보간법을 사용한 방법보다 더 좋은 성능을 보였다.