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Sung-Ryul Lee,
Hyoung-Kyu Kim,
In-Sung Song,
Jaeboum Youm,
Louise Anne Dizon,
Seung-Hun Jeong, Tae-Hee Ko,
Hae-Jin Huh,
Kyoung Soo Ko,
Byoung Doo Rhee,
Nari Kim,
Jin Han
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ABSTRACT: Glucocorticoids (GCs) affect most physiological systems and are the most frequently used drugs for multiple disorders and organ transplantation. GC functions depend on a balance between circulating GC and cytoplasmic glucocorticoid receptor II (GR). Mitochondria individually enclose circular, double-stranded DNA that is expressed and replicated in response to nuclear-encoded factors imported from the cytoplasm. Fine-tuning and response to cellular demands should be coordinately regulated by the nucleus and mitochondria. Thus, mitochondrial-nuclear interaction is vital to optimal mitochondrial function. Elucidation of the direct and indirect effects of steroids, including GCs, on mitochondria is an important and emerging field of research. Mitochondria may also be under GC control because GRs are present in mitochondria and glucocorticoid response elements (GREs) reside in the mitochondrial genome. Therefore, mitochondrial gene expression can be regulated by GCs via at least two different mechanisms: direct action on mitochondrial DNA and oxidative phosphorylation (OXPHOS) genes or by an indirect effect through interaction with nuclear genes. In this review, we outline possible mechanisms of regulation of mitochondrial genes in response to GCs in view of translocation of the GR into mitochondria and the possible regulation of OXPHOS genes by GREs in the mitochondrial genome.
Progress in Biophysics and Molecular Biology 04/2013; · 3.20 Impact Factor
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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
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ABSTRACT: Telmisartan is an angiotensin II receptor blocker and partial peroxisome proliferator-activated receptor gamma agonist that modulates the renin-angiotensin-aldosterone system. It is used primarily to manage hypertension, diabetic nephropathy, and congestive heart failure. Recent studies have reported that myocardial infarction (MI) has occurred in telmisartan-treated patients. The purpose of the study was to investigate the specific conditions and underlying mechanisms that may result in telmisartan-induced MI. We evaluated the effect of telmisartan on whole hearts, cardiomyocytes, and cardiac sarcolemmal ion channels. Hearts of 8-week-old male Sprague-Dawley rats were perfused with 3, 10, 30, or 100 μM telmisartan or losartan or with normal Tyrode's solution (control) for 3 h. We found that telmisartan induced myocardial infarction, with an infarct size of 21 % of the total at 30 μM (P < 0.0001) and 63 % of the total area at 100 μM (P < 0.001). Telmisartan also induced cardiac dysfunction (e.g., decreased heart rate, diminished coronary flow, hypercontracture, and arrhythmia). Confocal microscopy demonstrated that 30 μM telmisartan significantly elevated the intracellular Ca(2+) level, leading to hypercontracture and cell death. Patch clamp analysis of isolated cardiomyocytes revealed that telmisartan induced Na(+) overload by slowing the inactivation of voltage-gated Na(+) current (I (Na)), activating the reverse mode of Na(+)-Ca(2+) exchanger activity, and causing Ca(2+) overload. Telmisartan significantly delayed the inactivation of the voltage-gated Na(+) channel, causing cytosolic Na(+) overload, prolonged action potential duration, and subsequent Ca(2+) overload. Above 30 μM, telmisartan may potentially cause cardiac cell death and MI.
Pflügers Archiv - European Journal of Physiology 10/2012; · 4.46 Impact Factor
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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
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ABSTRACT: 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.
Nutrition research and practice 06/2012; 6(3):226-31. · 1.08 Impact Factor
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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
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ABSTRACT: 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.
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+).
These findings suggest that NecroX-5 may act as a mitochondrial Ca(2+) uniporter inhibitor to protect cardiac mitochondria against HR damage.
Cardiovascular research 03/2012; 94(2):342-50. · 5.80 Impact Factor
