12 results on '"Woong Bi Jang"'
Search Results
2. Pharmacological inhibition of mTOR attenuates replicative cell senescence and improves cellular function via regulating the STAT3-PIM1 axis in human cardiac progenitor cells
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Ji Hye Park, Na Kyoung Lee, Hye Ji Lim, Seung taek Ji, Yeon-Ju Kim, Woong Bi Jang, Da Yeon Kim, Songhwa Kang, Jisoo Yun, Jong seong Ha, Hyungtae Kim, Dongjun Lee, Sang Hong Baek, and Sang-Mo Kwon
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Medicine ,Biochemistry ,QD415-436 - Abstract
Abstract The mammalian target of rapamycin (mTOR) signaling pathway efficiently regulates the energy state of cells and maintains tissue homeostasis. Dysregulation of the mTOR pathway has been implicated in several human diseases. Rapamycin is a specific inhibitor of mTOR and pharmacological inhibition of mTOR with rapamycin promote cardiac cell generation from the differentiation of mouse and human embryonic stem cells. These studies strongly implicate a role of sustained mTOR activity in the differentiating functions of embryonic stem cells; however, they do not directly address the required effect for sustained mTOR activity in human cardiac progenitor cells. In the present study, we evaluated the effect of mTOR inhibition by rapamycin on the cellular function of human cardiac progenitor cells and discovered that treatment with rapamycin markedly attenuated replicative cell senescence in human cardiac progenitor cells (hCPCs) and promoted their cellular functions. Furthermore, rapamycin not only inhibited mTOR signaling but also influenced signaling pathways, including STAT3 and PIM1, in hCPCs. Therefore, these data reveal a crucial function for rapamycin in senescent hCPCs and provide clinical strategies based on chronic mTOR activity.
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- 2020
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3. Author Correction: Human cardiac stem cells rejuvenated by modulating autophagy with MHY-1685 enhance the therapeutic potential for cardiac repair
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Ji Hye Park, Hyeok Kim, Hyung Ryong Moon, Bong-Woo Park, Jae-Hyun Park, Woo-Sup Sim, Jin-Ju Kim, Hye Ji Lim, Yeon-Ju Kim, Seung Taek Ji, Woong Bi Jang, Vinoth Kumar Rethineswaran, Le Thi Hong Van, Ly Thanh Truong Giang, Jisoo Yun, Jong Seong Ha, Kiwon Ban, Hae Young Chung, Sang Hong Baek, Hun-Jun Park, and Sang-Mo Kwon
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Clinical Biochemistry ,Molecular Medicine ,Molecular Biology ,Biochemistry - Published
- 2022
4. AGR2 is a target of canonical Wnt/β-catenin signaling and is important for stemness maintenance in colorectal cancer stem cells
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Yun Hak Kim, Ji Hye Park, Jong Seong Ha, Songhwa Kang, Shreekrishna Lamichane, Yeon-Ju Kim, Da Yeon Kim, Li Dehua, Seung Taek Ji, Sang-Mo Kwon, Seok Yun Jung, Jisoo Yun, Woong Bi Jang, and Babita Dahal Lamichane
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0301 basic medicine ,Colorectal cancer ,Biophysics ,AGR2 ,Biology ,Stem cell marker ,Biochemistry ,Metastasis ,03 medical and health sciences ,Mucoproteins ,0302 clinical medicine ,Cancer stem cell ,Cell Line, Tumor ,Spheroids, Cellular ,medicine ,Humans ,Gene Silencing ,Neoplasm Metastasis ,Wnt Signaling Pathway ,Molecular Biology ,beta Catenin ,Oncogene Proteins ,Oncogene ,Gene Expression Profiling ,Wnt signaling pathway ,Cell Biology ,HCT116 Cells ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Wnt Proteins ,HEK293 Cells ,030104 developmental biology ,030220 oncology & carcinogenesis ,Neoplastic Stem Cells ,Cancer research ,Stem cell ,Colorectal Neoplasms ,Signal Transduction - Abstract
Colorectal cancer is one of the leading causes of cancer-related deaths. Due to relapse after current therapy regimens, cancer stem cells (CSCs) are being studied to target this small tumor-initiating population. Anterior gradient 2 (AGR2), a disulfide isomerase protein, is a well-known pro-oncogenic/metastatic oncogene overexpressed in various tumor tissues, including colon cancer. We found that AGR2 was a novel stem cell marker that was regulated by the canonical Wnt/β-catenin pathway in colon CSCs. AGR2 was highly co-expressed with surface stem cell markers in spheroidal culture. Silencing of AGR2 resulted in decreased sphere-forming ability and down-regulated expression of stem cell markers, whereas the opposite effects were seen with AGR2 overexpression. Moreover, patients with high β-catenin and AGR2 expression showed lower overall survival than those with low expression. In conclusion, our study describes a novel role for AGR2 as a stem cell marker that is highly regulated by canonical Wnt/β-catenin signaling in colorectal cancer.
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- 2019
5. Basic helix-loop-helix transcription factor Twist1 is a novel regulator of anterior gradient protein 2 homolog (AGR2) in breast cancer
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Le Thi Hong Van, Jisoo Yun, Woong Bi Jang, Dong Hwan Kim, Parkyong Song, Seung Taek Ji, Yeon-Ju Kim, Seong Jang Kim, Ji Hye Park, Songhwa Kang, Jong Seong Ha, Ly Thanh Truong Giang, Da Yeon Kim, Vinoth Kumar Rethineswaran, Sang-Mo Kwon, and Seok Yun Jung
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0301 basic medicine ,animal structures ,Biophysics ,AGR2 ,Breast Neoplasms ,Biology ,Biochemistry ,Small hairpin RNA ,03 medical and health sciences ,Mucoproteins ,0302 clinical medicine ,Breast cancer ,Cell Movement ,Cell Line, Tumor ,medicine ,Humans ,Promoter Regions, Genetic ,Protein disulfide-isomerase ,Molecular Biology ,Transcription factor ,Anterior Gradient Protein 2 Homolog ,Cell Proliferation ,Oncogene Proteins ,Basic helix-loop-helix ,Endoplasmic reticulum ,Twist-Related Protein 1 ,Nuclear Proteins ,Cell Biology ,Middle Aged ,medicine.disease ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,Female - Abstract
Anterior gradient protein 2 homolog (AGR2) belongs to the disulfide isomerase family of endoplasmic reticulum proteins. Itis overexpressed in several types of solid tumors, including tumors of the prostate, lung, and pancreas. However, the role of AGR2 in breast cancer and the regulatory mechanisms underlying AGR2 protein expressionare not fullyunderstood. We demonstrated that AGR2 levels are increased under hypoxic conditions and in breast cancer tumors. Mechanistically, Twist1 binds to, and activates the AGR2 promoter via an E-box sequence. Under hypoxic conditions, the increased expression of ARG2 is attenuated when Twist1 levels are reduced by shRNA. Conversely, Twist1 overexpression fully reverses decreased AGR2 levels upon HIF-1α knockdown. Notably, AGR2 is required for Twist1-induced proliferation, migration, and invasion of breast cancer cells. Collectively, these findings extend our understanding of AGR2 regulation in breast cancer and may contribute to development of Twist1-AGR2 targeting therapeutics for breast cancer.
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- 2019
6. 3D bioprinted tissue-specific spheroidal multicellular microarchitectures for advanced cell therapy
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Sanskrita Das, Sang-Mo Kwon, Yejin Park, Jinah Jang, Geunseon Ahn, Uijung Yong, Seung Taek Ji, and Woong Bi Jang
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Cell ,Biomedical Engineering ,Cell- and Tissue-Based Therapy ,Microextrusion ,Bioengineering ,Nanotechnology ,Matrix (biology) ,Biochemistry ,law.invention ,Biomaterials ,Cell therapy ,law ,medicine ,Viability assay ,3D bioprinting ,Decellularization ,Tissue Engineering ,Tissue Scaffolds ,Chemistry ,Bioprinting ,Endothelial Cells ,General Medicine ,Multicellular organism ,medicine.anatomical_structure ,Printing, Three-Dimensional ,Biotechnology - Abstract
Intercellular interaction is the most crucial factor in promoting cell viability and functionality in an engineered tissue system. Of the various shapes available for cell-laden constructs, spheroidal multicellular microarchitectures (SMMs) have been introduced as building blocks and injectable cell carriers with substantial cell-cell and cell-extracellular matrix (ECM) interactions. Here, we developed a precise and expeditious SMM printing method that can create a tissue-specific microenvironment and thus be potentially useful for cell therapy. This printing strategy is designed to manufacture SMMs fabricated with optimal bioink blended with decellularized ECM and alginate to enhance the functional performance of the encapsulated cells. Experimental results showed that the proposed method allowed for size controllability and mass production of SMMs with high cell viability. Moreover, SMMs co-cultured with endothelial cells promoted lineage-specific maturation and increased functionality compared to monocultured SMMs. Overall, it was concluded that SMMs have the potential for use in cell therapy due to their high cell retention and proliferation rate compared to single-cell injection, particularly for efficient tissue regeneration after myocardial infarction. This study suggests that utilizing microextrusion-based 3D bioprinting technology to encapsulate cells in cell-niche-standardized SMMs can expand the range of possible applications.
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- 2021
7. Human cardiac stem cells rejuvenated by modulating autophagy with MHY-1685 enhance the therapeutic potential for cardiac repair
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Jae-Hyun Park, Hun-Jun Park, Sang Hong Baek, Woo-Sup Sim, Jong Seong Ha, Jin-Ju Kim, Ly Thanh Truong Giang, Hae Young Chung, Vinoth Kumar Rethineswaran, Le Thi Hong Van, Hyeok Kim, Jisoo Yun, Hyung Ryong Moon, Ji Hye Park, Woong Bi Jang, Kiwon Ban, Hye Ji Lim, Bong-Woo Park, Seung Taek Ji, Yeon-Ju Kim, and Sang-Mo Kwon
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Senescence ,Male ,Cell type ,Cardiac fibrosis ,Clinical Biochemistry ,Biology ,Biochemistry ,Article ,medicine ,Autophagy ,Humans ,Regeneration ,Molecular Biology ,PI3K/AKT/mTOR pathway ,Cells, Cultured ,Cellular Senescence ,Stem-cell therapies ,Regeneration (biology) ,Myocardium ,Stem Cells ,TOR Serine-Threonine Kinases ,Cell Differentiation ,medicine.disease ,Fibrosis ,Cell biology ,Transplantation ,Molecular Medicine ,Stem cell ,Reactive Oxygen Species ,Heart stem cells ,Cell aging ,Myoblasts, Cardiac ,Signal Transduction ,Stem Cell Transplantation - Abstract
Stem cell-based therapies with clinical applications require millions of cells. Therefore, repeated subculture is essential for cellular expansion, which is often complicated by replicative senescence. Cellular senescence contributes to reduced stem cell regenerative potential as it inhibits stem cell proliferation and differentiation as well as the activation of the senescence-associated secretory phenotype (SASP). In this study, we employed MHY-1685, a novel mammalian target of rapamycin (mTOR) inhibitor, and examined its long-term priming effect on the activities of senile human cardiac stem cells (hCSCs) and the functional benefits of primed hCSCs after transplantation. In vitro experiments showed that the MHY-1685‒primed hCSCs exhibited higher viability in response to oxidative stress and an enhanced proliferation potential compared to that of the unprimed senile hCSCs. Interestingly, priming MHY-1685 enhanced the expression of stemness-related markers in senile hCSCs and provided the differentiation potential of hCSCs into vascular lineages. In vivo experiment with echocardiography showed that transplantation of MHY-1685‒primed hCSCs improved cardiac function than that of the unprimed senile hCSCs at 4 weeks post-MI. In addition, hearts transplanted with MHY-1685-primed hCSCs exhibited significantly lower cardiac fibrosis and higher capillary density than that of the unprimed senile hCSCs. In confocal fluorescence imaging, MHY-1685‒primed hCSCs survived for longer durations than that of the unprimed senile hCSCs and had a higher potential to differentiate into endothelial cells (ECs) within the infarcted hearts. These findings suggest that MHY-1685 can rejuvenate senile hCSCs by modulating autophagy and that as a senescence inhibitor, MHY-1685 can provide opportunities to improve hCSC-based myocardial regeneration., Heart disease: keeping cardiac stem cells younger Stem cells for repairing damaged hearts could be kept in a younger and more viable state using a drug called MHY-1685 which assists processes that resist cell aging. Using stem cells to repair damaged heart tissue requires millions of cells but culturing a suitable cell type often causes many cells to age and become less viable. Ji Hye Park at Pusan University, Yangsan, South Korea, and colleagues explored the potential of MHY-1685 to rejuvenate human cardiac stem cells (hCSCs). The drug enhances a maintenance process called autophagy, which clears cells of worn-out components. Exposure to MHY-1685 generated stem cell populations that proved more effective than unexposed cells at repairing damaged heart tissue when transplanted into rats. Its potential for producing cells for treating patients should be explored.
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- 2020
8. Oleuropein attenuates hydrogen peroxide-induced autophagic cell death in human adipose-derived stem cells
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Da Yeon Kim, Ji Hye Park, Jisoo Yun, Sang-Mo Kwon, Songhwa Kang, Seok Yun Jung, Jong Seong Ha, Seung Taek Ji, Woong Bi Jang, and Yeon-Ju Kim
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0301 basic medicine ,Programmed cell death ,Iridoid Glucosides ,Cell ,Biophysics ,Apoptosis ,AMP-Activated Protein Kinases ,Biochemistry ,Cell therapy ,03 medical and health sciences ,0302 clinical medicine ,Autophagy ,medicine ,Autophagy-Related Protein-1 Homolog ,Humans ,Iridoids ,Progenitor cell ,Molecular Biology ,Cells, Cultured ,PI3K/AKT/mTOR pathway ,Chemistry ,Mesenchymal stem cell ,Intracellular Signaling Peptides and Proteins ,Mesenchymal Stem Cells ,Hydrogen Peroxide ,Cell Biology ,030104 developmental biology ,medicine.anatomical_structure ,Adipose Tissue ,Cytoprotection ,030220 oncology & carcinogenesis ,Cancer research ,Signal Transduction - Abstract
Mesenchymal stem cells (MSCs) are multipotent progenitor cells with self-renewing properties; thus, transplanting functionally enhanced MSCs might be a promising strategy for cell therapy against ischemic diseases. However, extensive oxidative damage in ischemic tissue affects the cell fate of transplanted MSCs, eventually resulting in cell damage and autophagic cell death. Oleuropein (OLP) is a bioactive compound isolated from olives and olive oil that harbors antioxidant properties. This study aimed to investigate the potential cytoprotective effects of OLP against oxidative stress and autophagic cell death in MSCs. We found that short-term priming with OLP attenuated H2O2-induced apoptosis by regulating the pro-apoptotic marker Bax and the anti-apoptotic markers Bcl-2 and Mcl-1. Notably, OLP inhibits H2O2 -induced autophagic cell death by modulating autophagy-related death signals, including mTOR (mammalian target of rapamycin), ULK1 (unc-51 like autophagy activating kinase 1), Beclin-1, AMPK (AMP-activated protein kinase), and LC3 (microtubule-associated protein 1a/1b-light chain 3). Our data suggest that OLP might reduce H2O2-induced autophagy and cell apoptosis in MSCs by regulating both the AMPK-ULK axis and the Bcl-2-Mcl-1 axis. Consequently, short-term cell priming with OLP might enhance the therapeutic effect of MSCs against ischemic vascular diseases, which provides an important potential improvement for emerging therapeutic strategies.
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- 2018
9. Adequate concentration of B cell leukemia/lymphoma 3 (Bcl3) is required for pluripotency and self-renewal of mouse embryonic stem cells via downregulation of Nanog transcription
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Da Yeon Kim, Songhwa Kang, Ji Hye Park, Seung Taek Ji, Jong Seong Ha, Sang Hong Baek, Woong Bi Jang, Sang-Mo Kwon, Seok Yun Jung, Jae Ho Kim, Yeon-Ju Kim, and Jisoo Yun
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0301 basic medicine ,Homeobox protein NANOG ,Regulation of gene expression ,Bcl3 ,Mouse embryonic stem cell ,Cell growth ,Cellular differentiation ,Nanog Homeobox Protein ,General Medicine ,Articles ,Biology ,Biochemistry ,Embryonic stem cell ,Nanog ,Cell biology ,03 medical and health sciences ,030104 developmental biology ,Self-renewal ,Ectopic expression ,Induced pluripotent stem cell ,Molecular Biology - Abstract
B cell leukemia/lymphoma 3 (Bcl3) plays a pivotal role in immune homeostasis, cellular proliferation, and cell survival, as a co-activator or co-repressor of transcription of the NF-κB family. Recently, it was reported that Bcl3 positively regulates pluripotency genes, including Oct4, in mouse embryonic stem cells (mESCs). However, the role of Bcl3 in the maintenance of pluripotency and self-renewal activity is not fully established. Here, we report the dynamic regulation of the proliferation, pluripotency, and self-renewal of mESCs by Bcl3 via an influence on Nanog transcriptional activity. Bcl3 expression is predominantly observed in immature mESCs, but significantly decreased during cell differentiation by LIF depletion and in mESC-derived EBs. Importantly, the knockdown of Bcl3 resulted in the loss of self-renewal ability and decreased cell proliferation. Similarly, the ectopic expression of Bcl3 also resulted in a significant reduction of proliferation, and the self-renewal of mESCs was demonstrated by alkaline phosphatase staining and clonogenic single cell-derived colony assay. We further examined that Bcl3-mediated regulation of Nanog transcriptional activity in mESCs, which indicated that Bcl3 acts as a transcriptional repressor of Nanog expression in mESCs. In conclusion, we demonstrated that a sufficient concentration of Bcl3 in mESCs plays a critical role in the maintenance of pluripotency and the self-renewal of mESCs via the regulation of Nanog transcriptional activity. [BMB Reports 2018; 51(2): 92-97].
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- 2018
10. MHY2233 Attenuates Replicative Cellular Senescence in Human Endothelial Progenitor Cells via SIRT1 Signaling
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Songhwa Kang, Dong Hyung Lee, Babita Dahal Lamichane, Sang Hong Baek, Da Yeon Kim, Ha Jong Seong, SeungTaek Ji, Ji Hye Park, Jisoo Yun, Shreekrishna Lamichane, Hae Young Chung, Sang-Mo Kwon, Woong Bi Jang, Hyung Ryong Moon, Li Dehua, Na Kyung Lee, and Yeon-Ju Kim
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0301 basic medicine ,Senescence ,Aging ,Article Subject ,Angiogenesis ,medicine.medical_treatment ,Biology ,medicine.disease_cause ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Progenitor cell ,lcsh:QH573-671 ,Sirtuin 1 ,lcsh:Cytology ,Cell Biology ,General Medicine ,Stem-cell therapy ,Cell biology ,030104 developmental biology ,biology.protein ,Stem cell ,030217 neurology & neurosurgery ,Oxidative stress ,Deacetylase activity - Abstract
Cardiovascular diseases (CVDs) are a major cause of death worldwide. Due to the prevalence of many side effects and incomplete recovery from pharmacotherapies, stem cell therapy is being targeted for the treatment of CVDs. Among the different types of stem cells, endothelial progenitor cells (EPCs) have great potential. However, cellular replicative senescence decreases the proliferation, migration, and overall function of EPCs. Sirtuin 1 (SIRT1) has been mainly studied in the mammalian aging process. MHY2233 is a potent synthetic SIRT1 activator and a novel antiaging compound. We found that MHY2233 increased the expression of SIRT1, and its deacetylase activity thereby decreased expression of the cellular senescence biomarkers, p53, p16, and p21. In addition, MHY2233 decreased senescence-associated beta-galactosidase- (SA-β-gal-) positive cells and senescence-associated secretory phenotypes (SASPs), such as the secretion of interleukin- (IL-) 6, IL-8, IL-1α, and IL-1β. MHY2233 treatment protected senescent EPCs from oxidative stress by decreasing cellular reactive oxygen species (ROS) levels, thus enhancing cell survival and function. The angiogenesis, proliferation, and migration of senescent EPCs were enhanced by MHY2233 treatment. Thus, MHY2233 reduces replicative and oxidative stress-induced senescence in EPCs. Therefore, this novel antiaging compound MHY2233 might be considered a potent therapeutic agent for the treatment of age-associated CVDs.
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- 2019
11. Cytoprotective Roles of a Novel Compound, MHY-1684, against Hyperglycemia-Induced Oxidative Stress and Mitochondrial Dysfunction in Human Cardiac Progenitor Cells
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Hae Young Chung, Woong Bi Jang, Babita Dahal Lamichane, Seung Taek Ji, Jisoo Yun, Songhwa Kang, Hyung Ryong Moon, Yeon-Ju Kim, Na Kyung Lee, Ji Hye Park, Jong Seong Ha, Sang Hong Baek, Da Yeon Kim, Shreekrishna Lamichane, Sang-Mo Kwon, and Seok Yun Jung
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0301 basic medicine ,Mitochondrial ROS ,Dynamins ,Aging ,Programmed cell death ,Article Subject ,Cell Survival ,Blotting, Western ,030204 cardiovascular system & hematology ,medicine.disease_cause ,Biochemistry ,Antioxidants ,GTP Phosphohydrolases ,Mitochondrial Proteins ,03 medical and health sciences ,Heart disorder ,0302 clinical medicine ,Diabetic cardiomyopathy ,Peroxynitrous Acid ,medicine ,Humans ,lcsh:QH573-671 ,Cells, Cultured ,chemistry.chemical_classification ,Reactive oxygen species ,lcsh:Cytology ,Stem Cells ,Membrane Proteins ,Cell Biology ,General Medicine ,medicine.disease ,Cell biology ,Mitochondria ,Oxidative Stress ,030104 developmental biology ,mitochondrial fusion ,chemistry ,Hyperglycemia ,Phosphorylation ,Reactive Oxygen Species ,Microtubule-Associated Proteins ,Oxidative stress ,Research Article ,Signal Transduction - Abstract
Diabetic cardiomyopathy (DCM) is tightly linked to heart disorders and dysfunction or death of the cardiomyocytes including resident cardiac progenitor cells (CPCs) in diabetic patients. In order to restore loss of function of resident or transplanted CPCs, much research has focused on novel therapeutic strategies including the discovery of novel function-modulating factors such as reactive oxygen species (ROS) scavengers. Here, we developed and defined a novel antioxidant, MHY-1684, for enhancing the angiogenic potential of CPCs against ROS-related DCM. Short-term treatment with MHY-1684 restored ROS-induced CPC cell death. Importantly, MHY-1684 decreased hyperglycemia-induced mitochondrial ROS generation and attenuated hyperglycemia-induced mitochondrial fragmentation. We observed that the activation process of both Drp1 (phosphorylation at the site of Ser616) and Fis-1 is drastically attenuated when exposed to high concentrations of D-glucose with MHY-1684. Interestingly, phosphorylation of Drp1 at the site of Ser637, which is an inhibitory signal for mitochondrial fusion, is restored by MHY-1684 treatment, suggesting that this antioxidant may affect the activation and inhibition of mitochondrial dynamics-related signaling and mitochondrial function in response to ROS stress. In conclusion, our finding of the novel compound, MHY-1684, as an ROS scavenger, might provide an effective therapeutic strategy for CPC-based therapy against diabetic cardiomyopathy.
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- 2018
- Full Text
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12. High Glucose Causes Human Cardiac Progenitor Cell Dysfunction by Promoting Mitochondrial Fission: Role of a GLUT1 Blocker
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Jae Ho Kim, Ji Hye Park, Sang-Mo Kwon, Seok Yun Jung, Jisoo Yun, He Yun Choi, Sang Hong Baek, Songhwa Kang, Da Yeon Kim, Seung Taek Ji, Yeon-Ju Kim, and Woong Bi Jang
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0301 basic medicine ,FIS1 ,medicine.medical_specialty ,Cell ,Diabetic cardiomyopathy ,030204 cardiovascular system & hematology ,Biology ,Mitochondrion ,Biochemistry ,03 medical and health sciences ,Cardiac progenitor cell ,0302 clinical medicine ,Downregulation and upregulation ,Internal medicine ,Drug Discovery ,medicine ,Viability assay ,Pharmacology ,Tube formation ,Fasentin ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Hyperglycemia ,Cancer research ,Mitochondrial dynamics ,Molecular Medicine ,Mitochondrial fission ,Original Article - Abstract
Cardiovascular disease is the most common cause of death in diabetic patients. Hyperglycemia is the primary characteristic of diabetes and is associated with many complications. The role of hyperglycemia in the dysfunction of human cardiac progenitor cells that can regenerate damaged cardiac tissue has been investigated, but the exact mechanism underlying this association is not clear. Thus, we examined whether hyperglycemia could regulate mitochondrial dynamics and lead to cardiac progenitor cell dysfunction, and whether blocking glucose uptake could rescue this dysfunction. High glucose in cardiac progenitor cells results in reduced cell viability and decreased expression of cell cycle-related molecules, including CDK2 and cyclin E. A tube formation assay revealed that hyperglycemia led to a significant decrease in the tube-forming ability of cardiac progenitor cells. Fluorescent labeling of cardiac progenitor cell mitochondria revealed that hyperglycemia alters mitochondrial dynamics and increases expression of fission-related proteins, including Fis1 and Drp1. Moreover, we showed that specific blockage of GLUT1 improved cell viability, tube formation, and regulation of mitochondrial dynamics in cardiac progenitor cells. To our knowledge, this study is the first to demonstrate that high glucose leads to cardiac progenitor cell dysfunction through an increase in mitochondrial fission, and that a GLUT1 blocker can rescue cardiac progenitor cell dysfunction and downregulation of mitochondrial fission. Combined therapy with cardiac progenitor cells and a GLUT1 blocker may provide a novel strategy for cardiac progenitor cell therapy in cardiovascular disease patients with diabetes.
- Published
- 2016
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