Seol-Hee Jeon

Taurine increases cell proliferation and generates an increase in [Mg2+]i accompanied by ERK 1/2 activation in human osteoblast cells

Taurine has been reported to influence bone metabolism, and its specific transport system, the taurine transporter, is expressed in osteoblasts. The mean [Mg2+]i was 0.51 ± 0.01 mM in normal culture media. Taurine caused an increase in [Mg2+]i by 0.72 ± 0.04 mM in human osteoblast (HOB) cells. This increment in [Mg2+]i was inhibited significantly by PD98059, nifedipine, lidocaine, and imipramine. Taurine was also shown to stimulate the activation of ERK 1/2. This taurine‐stimulated ERK 1/2 activation was inhibited by PD98059. In the present study, taurine was shown to increase cell proliferation and generate an increase in [Mg2+]i accompanied by ERK 1/2 activation in HOB cells.

The antioxidant, taurine reduced lipopolysaccharide (LPS)-induced generation of ROS, and activation of MAPKs and Bax in cultured pneumocytes.

Lipopolysaccharide (LPS) can cause damage to the epithelia of the respiratory tract. However, taurine can protect the lung tissue from such oxidant-induced inflammation. This study examined the effects of a LPS treatment on the intracellular calcium levels ([Ca(2+)]i) as well as the specific mechanisms of LPS-induced cell death in pneumocytes. In addition, the effects of taurine on the LPS-induced increase in the accumulation of reactive oxygen species (ROS) in pneumocytes were investigated. The [Ca(2+)]i in cultured pneumocytes was determined using microfluorescence techniques. The level of activation of the mitogen-activated protein kinases (MAPKs) and Bax protein were measured by Western blotting. LPS at 10 and 100 ng/ml induced cell death and decreased the viability of MRC-5 cells. Moreover, the intracellular Ca(2+) and ROS levels were increased by LPS. The LPS treatment led to the phosphorylation of ERK1/2, JNK and the activation of Bax. A pretreatment with 20 mM taurine reduced the LPS-induced production of ROS and MARK activity. These results show that a LPS treatment induces cell death in MRC-5 cells by increasing the intracellular ROS and Ca(2+) levels. The increase in the intracellular level of ROS promotes MAPKs activation and Bax translocation. Overall, LPS induces lung cell death by activating MAPKs. Furthermore, taurine decreased the LPS-induced generation of ROS and activation of MAPK and Bax.

Effects of nortriptyline on QT prolongation: a safety pharmacology study.

Nortriptyline, a second-generation tricyclic antidepressant, is an active metabolite of amitriptyline. Amitriptyline induces QT prolongation and torsades de pointes (TdP), which causes sudden death. We studied the cardiovascular safety of nortriptyline, including QT prolongation risk. We examined the effects of nortriptyline on the cardiovascular system in vivo and in vitro in accordance with the ICH-S7B guideline. We tested its effect on QT interval in conscious telemetered dogs. We also performed in vitro electrophysiological studies on hERG tail currents using stably transfected human embryonic kidney 293 (HEK293) cells. Action potential parameters were studied in isolated rabbit purkinje fibers. Nortriptyline dose-dependently blocked hERG current, with a tail IC50 value of 2.20 ± 0.09 μM (n = 4). In the APD assay, total amplitude, Vmax, and resting membrane potential were not significantly changed by 1 μM nortriptyline, but nortriptyline at 0.3 and 1 μM shortened APD50 and APD90. Nortriptyline did not affect QTcV at 2 or 6 mg/kg, but slightly increased QTcV at 20 mg/kg. In conclusion, it is unlikely that nortriptyline affects the ventricular repolarization process at therapeutic dosages.

Taurine reduces FK506-induced generation of ROS and activation of JNK and Bax in Madin Darby canine kidney cells

The immunosuppressive compound FK506 has been successfully used in kidney and liver transplant recipients. However, the compound can induce significant side effects on kidney function. Taurine is a potent free radical scavenger that attenuates a variety of renal diseases that are the consequence of excessive oxygen free radical damage. The purpose of this study was to investigate FK506-mediated death of Madin Darby canine kidney (MDCK) cells, in relation to reactive oxygen species (ROS) production. We determined the calcium (Ca2+) and magnesium (Mg2+) concentration in cultured MDCK cells by microfluorescence techniques and the level of activation of c-Jun-N-terminal kinase (JNK), extracellular signal regulated kinases (ERK), Bcl-2 and Bax proteins by Western blot. Treatment with 10 μM FK506 induced apoptosis in MDCK cells by increasing the level of intracellular ROS and Ca2+ and by decreaseing the level of intracellular Mg2+. This increase in intracellular ROS promoted JNK and Bax activation, which increased FK506-induced MDCK cell death. Taurine reduced the FK506-induced generation of ROS and activation of JNK and Bax. The results indicate that taurine can prevent FK506-induced kidney toxicity.

Immunosuppressant FK506 decreases the intracellular magnesium in the human osteoblast cell by inhibiting the ERK1/2 pathway

AIMS Previous studies reported that FK506 influences bone mineralizing and hypomagnesemia, and also has immune modifying properties. This study examined whether or not the function of Mg2+ in bone metabolism plays a role in the loss of bone volume caused by immunosuppressants. MAIN METHODS The effects of the FK506 treatment on the intracellular magnesium and lactate dehydrogenase (LDH) activity were examined in cultured human osteoblasts (HOB) cells. The magnesium concentration was determined using microfluorescence techniques and atomic absorption spectrophotometry. Western blotting was used to measure the level of extracellular signal-regulated kinases 1/2 (ERK 1/2) activation. KEY FINDINGS FK506 (0.1 microM) did not affect cell death in HOB cells after a 24 hour treatment but decreased the level of ERK 1/2 activation. In HOB cells, the mean [Mg2+]i after exposure to a 1 mM extracellular Mg2+ ([Mg2+]o) buffer was 0.53+/-0.01 mM (n=25). Exposure to 100 nM FK506 produced a significant decrease in [Mg2+]i (0.41+/-0.01 mM). The ERK inhibitor (PD98059) and FK506 produced similar effects but they were not cumulative. SIGNIFICANCE This study examined the role of ERK1/2 activation on the regulation of magnesium in HOB. These results suggest that the inhibition of ERK phosphorylation is an essential intermediate in the effects of FK506 on magnesium. Overall, FK506 causes bone disorders partly by decreasing [Mg2+]i accompanied by the inhibition of ERK 1/2.

The Cardiovascular Depression Caused by Bee Venom in Sprague–Dawley Rats Associated with a Decrease of Developed Pressure in the Left Ventricular and the Ratio of Ionized Calcium/Ionized Magnesium

Bee venom (BV) has been used in Oriental medicine to treat inflammatory diseases, such as tendonitis, bursitis, and rheumatoid arthritis, despite the sensitivity of the victims and toxicity of the venom. This study examined the mechanisms for the effects of BV on the cardiovascular system in rats. The arterial pressure and heart rate (HR) were measured in anesthetized rats. In addition, the left ventricular development pressure (LVDP) and total magnesium efflux ([Mg]e) in isolated perfused hearts, the vascular tonic responses in the isolated aorta, and the blood ionic and biochemical changes were determined simultaneously. In the anesthetized rats, the mean arterial pressure, systolic pressure, and pulse pressure were reduced by BV in a dose-dependent manner, even though the HR was increased. BV had no effects on the relaxation of phenylephrine- or KCl-induced contraction of the aortic rings. In the isolated hearts, BV generated a reversible decrease in the LVDP and velocity with changes in pressure, which were accompanied by increases in the HR and [Mg]e. BV increased the plasma ionized and total magnesium concentrations, and decreased the total magnesium level in the red blood cells. The ratio of ionized calcium/ionized magnesium was also decreased by the BV treatment. BV caused a detectable increase in blood creatine kinase, glutamic oxaloacetic transaminase, and lactic dehydrogenase, as well as a decrease in the blood total protein albumin and globulin levels. These results suggest that BV induces cardiovascular depression by decreasing the cardiac pressure and increasing the ionized magnesium concentration in the blood.

Blood Hemolysis of Implantable Artificial Lung

The purpose of this study was to investigate the effect of multiple mechanical forces in hemolysis for usage as intravascular lung assist device. Specific attention was focused on the effect of membrane vibration. The results of experimental, PZT materials were used as an exciting system to improve efficiency of blood suitability of hollow fiber membrane for development of new intravascular lung assist device.

Blood Electrolyte Homeostasis of Rat after High-intensive Swimming Training

In sports medicine, very little attention has been given to magnesium compared with potassium and calcium. Magnesium ions (Mg²⁺) play a central role of neuronal activity, cardiac excitability, neuromuscular transmission, muscular contraction, vasomotor tone, and blood pressure significantly related to physical performance. Exercise is a potent stressor that appears to lead to magnesium depletion through alterations on blood magnesium levels as well as increased sweat and urine excretion. After exhausted swimming (3-4 hrs) in rats, the iCa²⁺/iMg²⁺ were significantly decreased. The Na⁺, iCa²⁺, iMg²⁺, and anion gap were significantly increased. These data suggest that exercise could alter blood iMg²⁺, iCa²⁺ and the ratio of iCa²⁺/iMg²⁺ and point to important uses for iMg²⁺ and the ratio of iCa²⁺/iMg²⁺ during the training and examination of athletic performance in sports medicine.

Design of the Implantable Artificial Lung using Computational Fluid Dynamics

An artificial implantable lung would be a useful device to support ARDS patients awaiting lung transplantation. In this study, the characteristic of fluid flow in the new type lung assist devices has been established using CFD. According to the modeling, it is believed that the tangential type module would be more beneficial to the fluid flow, and 2 ports would influence better than 1 port. However, such results are simple modeling by CFD, and therefore need to be confirmed by actual experiments.