High Glucose Causes Human Cardiac Progenitor Cell Dysfunction by Promoting Mitochondrial Fission: Role of a GLUT1 Blocker

Choi, He Yun; Park, Ji Hye; Jang, Woong Bi; Ji, Seung Taek; Jung, Seok Yun; Kim, Da Yeon; Kang, Songhwa; Kim, Yeon Ju; Yun, Jisoo; Kim, Jae Ho; Baek, Sang Hong; Kwon, Sang-Mo

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저자정보: Choi, He Yun (Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, Pusan National University) Park, Ji Hye (Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, Pusan National University) Jang, Woong Bi (Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, Pusan National University) Ji, Seung Taek (Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, Pusan National University) Jung, Seok Yun (Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, Pusan National University) Kim, Da Yeon (Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, Pusan National University) Kang, Songhwa (Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, Pusan National University) Kim, Yeon Ju (Laboratory for Vascular Medicine a) Yun, Jisoo Kim, Jae Ho Baek, Sang Hong Kwon, Sang-Mo

저널정보: 한국응용약물학회 Biomolecules & Therapeutics(구 응용약물학회지) Biomolecules & therapeutics 제24권 제4호

발행연도: 2016.1

수록면: 363 - 370 (8page)

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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.

#Cardiac progenitor cell #Hyperglycemia #Fasentin #Mitochondrial dynamics #Diabetic cardiomyopathy

참고문헌 (19)

참고문헌 신청

Archer, S. L / 2013 / Mitochondrial dynamics--mitochondrial fission and fusion in human diseases / N. Engl. J. Med 369:2236~2251

Bell, D. S / 2003 / Heart failure: the frequent, forgotten, and often fatal complication of diabetes / Diabetes Care 26:2433~2441

Choi, S. H / 2013 / Amine-enriched surface modification facilitates expansion, attachment, and maintenance of human cardiacderived c-kit positive progenitor cells / Int. J. Cardiol 168:100~107

Davidson, J. A / 2009 / Is hyperglycemia a causal factor in cardiovascular disease? Does proving this relationship really matter? Yes / Diabetes Care 32:s331~s333

Di Lorenzo, T. P / 2007 / Translational mini-review series on type 1 diabetes: Systematic analysis of T cell epitopes in autoimmune diabetes / Clin. Exp. Immunol 148:1~16

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