• Bulletin of the Korean Chemical Society
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• v.30 no.1
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• pp.236-238
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• 2009

• Molecules and Cells
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• v.26 no.2
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• pp.152-157
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• 2008

Caspases play critical roles in the execution of apoptosis. Caspase-3 and caspase-7 are closely related in sequence as well as in substrate specificity. The two caspases have overlapping substrate specificities with special preference for the DEVD motif. However, they are targeted to different subcellular locations during apoptosis, implying the existence of substrates specific for one or other caspase. To identify new caspase-7 substrates, we digested cell lysates obtained from the caspase-3-deficient MCF-7 cell line with purified recombinant caspase-7, and analyzed spots that disappeared or decreased by 2-DE (we refer to this as the caspase-7 degradome). Several proteins with various cellular functions underwent caspase-7-dependent proteolysis. The substrates of capase-7 identified by the degradomic approach were rather different from those of caspase-3 (Proteomics, 4, 3429-3435, 2004). Among the candidate substrates, we confirmed that Valosin-containing protein (VCP) was cleaved by both capspase-7 and caspase-3 in vitro and during apoptosis. Cleavage occurred at both $DELD^{307}$ and $DELD^{580}$. The degradomic study yielded several candidate caspase-7 substrates and their further analysis should provide valuables clues to the functions of caspase-7 during apoptosis.

• Molecules and Cells
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• v.24 no.2
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• pp.261-267
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• 2007

Apoptotic signals are typically accompanied by activation of aspartate-specific cysteine proteases called caspases, and caspase-3 and -7 play crucial roles in the execution of apoptosis. Previously, using the proteomic approach, protein disulfide isomerase (PDI) was found to be a candidate substrate of caspase-7. This abundant 55 kDa protein introduces disulfide bonds into proteins (via its oxidase activity) and catalyzes the rearrangement of incorrect disulfide bonds (via its isomerase activity). PDI is abundant in the ER but is also found in non-ER locations. In this study we demonstrated that PDI is cleaved by caspase-3 and -7 in vitro. In addition, in vivo experiment showed that it is cleaved during etoposide-induced apoptosis in HL-60 cells. Subcellular fractionation showed that PDI was also present in the cytosol. Furthermore, only cytosolic PDI was clearly digested by caspase-3 and -7. It was also confirmed by confocal image analysis that PDI and caspase-7 partially co-localize in both resting and apoptotic MCF-7 cells. Overexpression of cytosolic PDI (ER retention sequence deleted) inhibited cell death after an apoptotic stimulus. These data indicate that cytosolic PDI is a substrate of caspase-3 and -7, and that it has an anti-apoptotic action.

• Journal of Ginseng Research
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• v.46 no.2
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• pp.255-265
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• 2022

Background: Ginsenoside Rb1, a bioactive component isolated from the Panax ginseng, acts as a remedy to prevent myocardial injury. However, it is obscure whether the cardioprotective functions of Rb1 are related to the regulation of endogenous metabolites, and its potential molecular mechanism still needs further clarification, especially from a comprehensive metabolomics profiling perspective. Methods: The mice model of acute myocardial ischemia (AMI) and oxygen glucose deprivation (OGD)-induced cardiomyocytes injury were applied to explore the protective effect and mechanism of Rb1. Meanwhile, the comprehensive metabolomics profiling was conducted by high-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (HPLC-Q/TOF-MS) and a tandem liquid chromatography and mass spectrometry (LC-MS). Results: Rb1 treatment profoundly reduced the infarct size and attenuated myocardial injury. The metabolic network map of 65 differential endogenous metabolites was constructed and provided a new inspiration for the treatment of AMI by Rb1, which was mainly associated with mitophagy. In vivo and in vitro experiments, Rb1 was found to improve mitochondrial morphology, mitochondrial function and promote mitophagy. Interestingly, the mitophagy inhibitor partly attenuated the cardioprotective effect of Rb1. Additionally, Rb1 markedly facilitated the phosphorylation of AMP-activated protein kinase α (AMPKα), and AMPK inhibition partially weakened the role of Rb1 in promoting mitophagy. Conclusions: Ginsenoside Rb1 protects acute myocardial ischemia injury through promoting mitophagy via AMPKα phosphorylation, which might lay the foundation for the further application of Rb1 in cardiovascular diseases.

• 대한약리학회:학술대회논문집
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• 2006.11a
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• pp.45-45
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• 2006

• Journal of Gastric Cancer
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• v.17 no.1
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• pp.33-42
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• 2017

Purpose: Endoscopic submucosal dissection (ESD) in early gastric cancer causes an artificial gastric ulcer and local inflammation that has a negative intraprocedural impact on additional laparoscopic gastrectomy in patients with noncurative ESD. In this study, we analyzed the effect of ESD on short-term surgical outcomes and evaluated the risk factors. Materials and Methods: From January 2003 to January 2013, 1,704 patients of the National Cancer Center underwent laparoscopic gastrectomy with lymph node dissection because of preoperative stage Ia or Ib gastric cancer. They were divided into 2 groups: (1) with preoperative ESD or (2) without preoperative ESD. Clinicopathologic factors and short-term surgical outcomes were retrospectively evaluated along with risk factors such as preoperative ESD. Results: Several characteristics differed between patients who underwent ESD-surgery (n=199) or surgery alone (n=1,505). The mean interval from the ESD procedure to the operation was 43.03 days. Estimated blood loss, open conversion rate, mean operation time, and length of hospital stay were not different between the 2 groups. Postoperative complications occurred in 23 patients (11.56%) in the ESD-surgery group and in 189 patients (12.56%) in the surgery-only group, and 3 deaths occurred among patients with complications (1 patient [ESD-surgery group] vs. 2 patients [surgery-only group]; P=0.688). A history of ESD was not significantly associated with postoperative complications (P=0.688). Multivariate analysis showed that male sex (P=0.008) and laparoscopic total or proximal gastrectomy (P=0.000) were independently associated with postoperative complications. Conclusions: ESD did not affect short-term surgical outcomes during and after an additional laparoscopic gastrectomy.

• BMB Reports
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• v.37 no.1
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• pp.35-44
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• 2004

Recently produced information on post-translational modifications makes it possible to interpret their biological regulation with new insights. Various protein modifications finely tune the cellular functions of each protein. Understanding the relationship between post-translational modifications and functional changes ("post-translatomics") is another enormous project, not unlike the human genome project. Proteomics, combined with separation technology and mass spectrometry, makes it possible to dissect and characterize the individual parts of post-translational modifications and provide a systemic analysis. Systemic analysis of post-translational modifications in various signaling pathways has been applied to illustrate the kinetics of modifications. Availability will advance new technologies that improve sensitivity and peptide coverage. The progress of "post-translatomics", novel analytical technologies that are rapidly emerging, offer a great potential for determining the details of the modification sites.

• Bulletin of the Korean Chemical Society
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• v.34 no.2
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• pp.673-676
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• 2013

• Journal of Microbiology and Biotechnology
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• v.18 no.2
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• pp.270-282
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• 2008

The yeast Saccharomyces cerevisiae has defense mechanisms identical to higher eukaryotes. It offers the potential for genome-wide experimental approaches owing to its smaller genome size and the availability of the complete sequence. It therefore represents an ideal eukaryotic model for studying cellular redox control and oxidative stress responses. S. cerevisiae Yap1 is a well-known transcription factor that is required for $H_2O_2$-dependent stress responses. Yap1 is involved in various signaling pathways in an oxidative stress response. The Gpx3 (Orp1/PHGpx3) protein is one of the factors related to these signaling pathways. It plays the role of a transducer that transfers the hydroperoxide signal to Yap1. In this study, using extensive proteomic and bioinformatics analyses, the function of the Gpx3 protein in an adaptive response against oxidative stress was investigated in wild-type, gpx3-deletion mutant, and gpx3-deletion mutant overexpressing Gpx3 protein strains. We identified 30 proteins that are related to the Gpx3-dependent oxidative stress responses and 17 proteins that are changed in a Gpx3-dependent manner regardless of oxidative stress. As expected, $H_2O_2$-responsive Gpx3-dependent proteins include a number of antioxidants related with cell rescue and defense. In addition, they contain a variety of proteins related to energy and carbohydrate metabolism, transcription, and protein fate. Based upon the experimental results, it is suggested that Gpx3-dependent stress adaptive response includes the regulation of genes related to the capacity to detoxify oxidants and repair oxidative stress-induced damages affected by Yap1 as well as metabolism and protein fate independent from Yap1.

• The Journal of the Korean dental association
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• v.55 no.7
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• pp.457-466
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• 2017

In the case of failed fixed implant prosthesis accompanied by abutment screw fracture, fractured screw fragment must be removed to use the existing implant fixtures. A 61-year-old male patient, who had a failed maxillary fixed implant prosthesis accompanied by three abutment screw fracture, hoped to reconstruct the maxillary implant prosthesis, while maintaining the existing implant fixtures. To use the existing implant fixtures, fractured screw fragments were removed. A maxillary implant overdenture using available existing implants was planned. Bar-attachment with Locator was used for implant splinting, denture stability, and retention. Final impression was taken after treatment of peri-implantitis. Jaw relation registration was taken to evaluate available interarch space for bar-attachment. After fabricating bar-attachment, centric relation was taken. Implant overdenture using bar-attachment with Locator was delivered after wax-denture evaluation. This case report showed that a satisfactory clinical result was achieved by implant overdenture using existing implant fixtures in a maxillary edentulous patient.