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Dive into the research topics where Tae Hee Ko is active.

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Featured researches published by Tae Hee Ko.


Cardiovascular Research | 2012

NecroX-5 prevents hypoxia/reoxygenation injury by inhibiting the mitochondrial calcium uniporter

Vu Thi Thu; Hyoung-Kyu Kim; Le Thanh Long; Sung-Ryul Lee; Tran My Hanh; Tae Hee Ko; Hye-Jin Heo; Nari Kim; Soon Ha Kim; Kyung Soo Ko; Byoung Doo Rhee; Jin Han

AIMS Preservation of mitochondrial function is essential to limit myocardial damage in ischaemic heart disease. We examined the protective effects and mechanism of a new compound, NecroX-5, on rat heart mitochondria in a hypoxia/reoxygenation (HR) model. METHODS AND RESULTS NecroX-5 reduced mitochondrial oxidative stress, prevented the collapse in mitochondrial membrane potential, improved mitochondrial oxygen consumption, and suppressed mitochondrial Ca(2+) overload during reoxygenation in an in vitro rat heart HR model. Furthermore, NecroX-5 reduced the ouabain- or histamine-induced increase in mitochondrial Ca(2+). CONCLUSION These findings suggest that NecroX-5 may act as a mitochondrial Ca(2+) uniporter inhibitor to protect cardiac mitochondria against HR damage.


Experimental and Molecular Medicine | 2013

Combination treatment with 2-methoxyestradiol overcomes bortezomib resistance of multiple myeloma cells

In-Sung Song; Yu Jeong Jeong; Seung Hun Jeong; Hye Jin Heo; Hyoung Kyu Kim; Sung Ryul Lee; Tae Hee Ko; Jae Boum Youm; Nari Kim; Kyung Soo Ko; Byoung Doo Rhee; Jin Han

Bortezomib is a proteasome inhibitor used for the treatment of relapsed/refractory multiple myeloma (MM). However, intrinsic and acquired resistance to bortezomib has already been observed in MM patients. In a previous report, we demonstrated that changes in the expression of mitochondrial genes lead to changes in mitochondrial activity and bortezomib susceptibility or resistance, and their combined effects contribute to the differential sensitivity or resistance of MM cells to bortezomib. Here we report that the combination treatment of bortezomib and 2-methoxyestradiol (2ME), a natural estrogen metabolite, induces mitochondria-mediated apoptotic cell death of bortezomib-resistant MM KMS20 cells via mitochondrial reactive oxygen species (ROS) overproduction. Bortezomib plus 2ME treatment induces a higher level of cell death compared with treatment with bortezomib alone and increases mitochondrial ROS and Ca2+ levels in KMS20 cells. Pretreatment with the antioxidant N-acetyl-L-cysteine scavenges mitochondrial ROS and decreases cell death after treatment with bortezomib plus 2ME in KMS20 cells. Moreover, we observed that treatment with bortezomib plus 2ME maintains the activation of c-Jun N-terminal kinase (JNK) and mitogen-activated protein kinase kinase kinase 4/7 (MKK4/7). Collectively, combination treatment with bortezomib and 2ME induces cell death via JNK-MKK4/7 activation by overproduction of mitochondrial ROS. Therefore, combination therapy with specific mitochondrial-targeting drugs may prove useful to the development of novel strategies for the treatment of bortezomib-resistant MM patients.


Nutrition Research and Practice | 2012

Independent beneficial effects of aged garlic extract intake with regular exercise on cardiovascular risk in postmenopausal women

Dae Yun Seo; Sung Ryul Lee; Hyoung Kyu Kim; Yeong Ho Baek; Yi Sub Kwak; Tae Hee Ko; Nari Kim; Byoung Doo Rhee; Kyoung Soo Ko; Byung Joo Park; Jin Han

The purpose of the study was to assess the effects of a 12 weeks aged garlic extract (AGE) regimen with regular exercise on cardiovascular disease (CVD) risk in postmenopausal women. A total of 30 postmenopausal women (54.4 ± 5.4 years) were randomly divided into the following four groups: Placebo (Placebo; n = 6), AGE intake (AGEI; n = 8), exercise and placebo (Ex + Placebo; n = 8), exercise and AGE (Ex + AGE; n = 8) groups. The AGE group consume 80 mg per day, and exercise groups performed moderate exercise (aerobic and resistance) three times per week. After 12 weeks of treatment, body composition, lipid profile, and CVD risk factors were analyzed. Body weight was significantly decreased in AGEI, Ex + Placebo, and Ex + AGE groups compared to baseline. Body fat % was significantly decreased in the AGEI and Ex + Placebo groups. Body mass index (BMI) was significantly decreased in the AGEI, Ex + Placebo, and Ex + AGE groups. Fat-free mass was significantly decreased in the AGEI group. Total cholesterol (TC) was significantly lower in the Ex + Placebo compared to the Placebo group. AGE supplementation or exercise effectively reduced low-density lipoprotein (LDL-C). Triglyceride (TG) was significantly increased in the AGEI group. Malondialdehyde (MDA) levels were significantly decreased in the AGEI, Ex + Placebo, and Ex + AGE compared to the placebo group. AGE supplementation reduced homocysteine levels regardless of whether the women also exercised. The present results suggest that AGE supplementation reduces cardiovascular risk factors independently of exercise in postmenopausal women.


Experimental and Molecular Medicine | 2016

Mitochondrial pyruvate dehydrogenase phosphatase 1 regulates the early differentiation of cardiomyocytes from mouse embryonic stem cells

Hye Jin Heo; Hyoung Kyu Kim; Jae Boum Youm; Sung Woo Cho; In-Sung Song; Sunyoung Lee; Tae Hee Ko; Nari Kim; Kyung Soo Ko; Byoung Doo Rhee; Jin Han

Mitochondria are crucial for maintaining the properties of embryonic stem cells (ESCs) and for regulating their subsequent differentiation into diverse cell lineages, including cardiomyocytes. However, mitochondrial regulators that manage the rate of differentiation or cell fate have been rarely identified. This study aimed to determine the potential mitochondrial factor that controls the differentiation of ESCs into cardiac myocytes. We induced cardiomyocyte differentiation from mouse ESCs (mESCs) and performed microarray assays to assess messenger RNA (mRNA) expression changes at differentiation day 8 (D8) compared with undifferentiated mESCs (D0). Among the differentially expressed genes, Pdp1 expression was significantly decreased (27-fold) on D8 compared to D0, which was accompanied by suppressed mitochondrial indices, including ATP levels, membrane potential, ROS and mitochondrial Ca2+. Notably, Pdp1 overexpression significantly enhanced the mitochondrial indices and pyruvate dehydrogenase activity and reduced the expression of cardiac differentiation marker mRNA and the cardiac differentiation rate compared to a mock control. In confirmation of this, a knockdown of the Pdp1 gene promoted the expression of cardiac differentiation marker mRNA and the cardiac differentiation rate. In conclusion, our results suggest that mitochondrial PDP1 is a potential regulator that controls cardiac differentiation at an early differentiation stage in ESCs.


The Korean Journal of Physiology and Pharmacology | 2016

Voluntary stand-up physical activity enhances endurance exercise capacity in rats

Dae Yun Seo; Sung Ryul Lee; Hyo Bum Kwak; Kyo Won Seo; Robin A. McGregor; Ji Young Yeo; Tae Hee Ko; Saranhuu Bolorerdene; Nari Kim; Kyung Soo Ko; Byoung Doo Rhee; Jin Han

Involuntary physical activity induced by the avoidance of electrical shock leads to improved endurance exercise capacity in animals. However, it remains unknown whether voluntary stand-up physical activity (SPA) without forced simulating factors improves endurance exercise capacity in animals. We examined the eff ects of SPA on body weight, cardiac function, and endurance exercise capacity for 12 weeks. Twelve male Sprague-Dawley rats (aged 8 weeks, n=6 per group) were randomly assigned to a control group (CON) or a voluntary SPA group. The rats were induced to perform voluntary SPA (lifting a load equal to their body weight), while the food height (18.0 cm) in cages was increased progressively by 3.5 every 4 weeks until it reached 28.5 cm for 12 weeks. The SPA group showed a lower body weight compared to the CON group, but voluntary SPA did not affect the skeletal muscle and heart weights, food intake, and echocardiography results. Although the SPA group showed higher grip strength, running time, and distance compared to the CON group, the level of irisin, corticosterone, genetic expression of mitochondrial biogenesis, and nuclei numbers were not affected. These findings show that voluntary SPA without any forced stimuli in rats can eff ectively reduce body weight and enhance endurance exercise capacity, suggesting that it may be an important alternative strategy to enhance endurance exercise capacity.


Pflügers Archiv: European Journal of Physiology | 2016

Cereblon in health and disease

Hyoung Kyu Kim; Tae Hee Ko; Bayalagmaa Nyamaa; Sung Ryul Lee; Nari Kim; Kyung Soo Ko; Byoung Doo Rhee; Chul-Seung Park; Bernd Nilius; Jin Han

Cereblon (CRBN) is a substrate receptor of the E3 ubiquitin ligase complex that has been linked to autosomal recessive non-syndromic mental retardation. Several key findings suggest diverse roles of CRBN, including its regulation of the large-conductance calcium- and voltage-activated potassium (BKCa) channels, regulation of thalidomide-binding proteins, and mediation of lenalidomide treatment in multiple myeloma. Recent studies also indicate that CRBN is involved in energy metabolism and negatively regulates AMP-activated protein kinase signaling. Mice with genetic depletion of CRBN are resistant to various stress conditions including a high-fat diet, endoplasmic reticulum stress, ischemia/reperfusion injury, and alcohol-related liver damage. In this review, we discuss the various roles of CRBN in human health and disease and suggest avenues for further research to enhance our basic knowledge and clinical application of CRBN.


Scientific Reports | 2017

Generation of PDGFRα Cardioblasts from Pluripotent Stem Cells.

Seon Pyo Hong; Sukhyun Song; Sung Woo Cho; Seungjoo Lee; Bong Ihn Koh; Hosung Bae; Kyun Hoo Kim; Jin-Sung Park; Hyo-Sang Do; Ilkyun Im; Hye Jin Heo; Tae Hee Ko; Jae-Hyeong Park; Jae Boum Youm; Seong-Jin Kim; Injune Kim; Jin Han; Yong-Mahn Han; Gou Young Koh

Isolating actively proliferating cardioblasts is the first crucial step for cardiac regeneration through cell implantation. However, the origin and identity of putative cardioblasts are still unclear. Here, we uncover a novel class of cardiac lineage cells, PDGFRα+Flk1− cardioblasts (PCBs), from mouse and human pluripotent stem cells induced using CsAYTE, a combination of the small molecules Cyclosporin A, the rho-associated coiled-coil kinase inhibitor Y27632, the antioxidant Trolox, and the ALK5 inhibitor EW7197. This novel population of actively proliferating cells is cardiac lineage–committed but in a morphologically and functionally immature state compared to mature cardiomyocytes. Most important, most of CsAYTE-induced PCBs spontaneously differentiated into functional αMHC+ cardiomyocytes (M+CMs) and could be a potential cellular resource for cardiac regeneration.


Pflügers Archiv: European Journal of Physiology | 2012

The angiotensin receptor blocker and PPAR-γ agonist, telmisartan, delays inactivation of voltage-gated sodium channel in rat heart: novel mechanism of drug action

Hyoung Kyu Kim; Jae Boum Youm; Sung Ryul Lee; Se Eun Lim; Sun-Young Lee; Tae Hee Ko; Le Thanh Long; Bernd Nilius; Du Nam Won; Jung Hyun Noh; Kyung Soo Ko; Byoung Doo Rhee; Nari Kim; Jin Han


Pflügers Archiv: European Journal of Physiology | 2015

Echinochrome A regulates phosphorylation of phospholamban Ser16 and Thr17 suppressing cardiac SERCA2A Ca2+ reuptake

Hyoung Kyu Kim; Jae Boum Youm; Seung Hun Jeong; Sung Ryul Lee; In Sung Song; Tae Hee Ko; Julius Ryan Pronto; Kyung Soo Ko; Byoung Doo Rhee; Nari Kim; Bernd Nilius; Natalia P. Mischchenko; Sergey A. Fedoreyev; Valentin A. Stonik; Jin Han


Pflügers Archiv: European Journal of Physiology | 2015

Influence of starvation on heart contractility and corticosterone level in rats

Sung Ryul Lee; Tae Hee Ko; Hyoung Kyu Kim; Jubert Marquez; Kyung Soo Ko; Byoung Doo Rhee; Jin Han

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