• The Korean Journal of Physiology and Pharmacology
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• v.13 no.2
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• pp.123-129
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• 2009

Aprotinin is used clinically in cardiopulmonary bypass surgery to reduce transfusion requirements and the inflammatory response. The mechanism of action for the anti-inflammatory effects of aprotinin is still unclear. We examined our hypothesis whether inhibitory effects of aprotinin on cytokine-induced inducible nitric oxide synthase (iNOS) expression (IL-$l\beta$ plus TNF-$\alpha$), reactive oxygen species (ROS) generation, and vascular smooth muscle cell (VSMC) proliferation were due to HO-l induction in rat VSMCs. Aprotinin induced HO-l protein expression in a dose-dependent manner, which was potentiated during inflammatory condition. Aprotinin reduced cytokine mixture (CM)-induced iNOS expression in a dose dependent manner. Furthermore, aprotinin reduced CM-induced ROS generation, cell proliferation, and phosphorylation of JNK but not of P38 and ERK1/2 kinases. Aprotinin effects were reversed by pre-treatment with the HO-l inhibitor, tin protoporphyrin IX (SnPPIX). HO-l is therefore closely involved in inflammatory-stimulated VSMC proliferation through the regulation of ROS generation and JNK phosphorylation. Our results suggest a new molecular basis for aprotinin anti-inflammatory properties.

• BMB Reports
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• v.42 no.9
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• pp.580-585
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• 2009

Dimethyl sulfoxide (DMSO) is widely used in chemistry and biology as a solvent and as a cryoprotectant. It is also used as a pharmaceutical agent for the treatment of interstitial cystitis and rheumatoid arthritis. Previous reports described DMSO as being reduced by methionine-S-sulfoxide reductase (MsrA). However, little is known about the DMSO reduction capability of methionine-R-sulfoxide reductase (MsrB) or its effect on the catalysis of methionine sulfoxide reduction. We show that mammalian MsrB2 and MsrB3 were unable to reduce DMSO. This compound inhibited MsrB2 activity but did not inhibit MsrB3 activity. We further determined that DMSO functions as an inhibitor of MsrA and MsrB2 in the reduction of methionine sulfoxides via different inhibition mechanisms. DMSO competitively inhibited MsrA activity but acted as a non-competitive inhibitor of MsrB2 activity. Our study also demonstrated that DMSO inhibits in vivo methionine sulfoxide reduction in yeast and mammalian cells.

• Molecules and Cells
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• v.20 no.3
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• pp.429-434
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• 2005

Lysophosphatidylcholine (lysoPC) induces vascular smooth muscle cell (VSMC) proliferation and migration, which has been proposed to initiate the intimal thickening in coronary atherosclerotic lesions. Berberine is an alkaloid in Berberis aquifolium and many other plants. Recently, it has been shown to have beneficial effects on the cardiovascular system, such as anti-hyperglycemic and cholesterol-lowering activity. In this study, we investigated its effects on lysoPC-induced VSMC proliferation and migration. Berberine inhibited lysoPC-induced DNA synthesis and cell proliferation in VSMCs, as well as migration of the lysoPC-stimulated VSMCs. It also inhibited the activation of extracellular signal-regulated kinases (ERKs) and reduced transcription factor AP-1 activity and the lysoPC-induced increases in intracellular reactive oxygen species (ROS). These results indicate that the inhibitory effects of berberine on lysoPC-stimulated VSMC proliferation and migration are attributable to inhibition of ROS generation and hence of activation of the ERK1/2 pathway. This suggests that berberine has potential in the prevention of atherosclerosis and restenosis.

• Archives of Pharmacal Research
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• v.26 no.4
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• pp.286-293
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• 2003

Several polyphenolic compounds and complex mixtures were isolated from brown algae species. The 1,1-diphenyl-2-picryhydarzyl (DPPH) radical scavenging activity and ferric reducing antioxidant power (FRAP) of these compounds were evaluated to determine their physiological usefulness as antioxidants for vascular protection. The antioxidative protection of low-density lipoprotein (LDL) was also evaluated and compared with that of catechin, because the generation of oxidized LDL is one of the most active and specific risk factors contributing to atherogenesis. Oral administration to rats of a commercially available sample ($VNP^{TM}$) containing 30% of these polyphenolic compounds and 70% dietary fiber revealed that the serum reducing capacity measured in terms of FRAP value was significantly elevated 30 min after the treatment, but declined rather quickly thereafter, indicating the good oral absorption of the compounds and their fast binding to the lumenal surface of the blood vessels. An eight-week, human, clinical trial (n=31) of $VNP^{TM}$ showed significant improvement in erectile function measured by IIEF (international index of erectile function) score. These results collectively demonstrated the usefulness of these polyphenolic compounds as fundamental chemopreventive agents against vascular risk factors originating from oxidative stress.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.5
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• pp.299-304
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• 2010

Losartan is a selective angiotensin II (Ang II) type 1 ($AT_1$) receptor antagonist which inhibits vascular smooth muscle cells (VSMCs) contraction and proliferation. We hypothesized that losartan may prevent cell proliferation by activating AMP-activated protein kinase (AMPK) in VSMCs. VSMCs were treated with various concentrations of losartan. AMPK activation was measured by Western blot analysis and cell proliferation was measured by MTT assay and flowcytometry. Losartan dose- and time-dependently increased the phosphorylation of AMPK and its downstream target, acetyl-CoA carboxylase (ACC) in VSMCs. Losartan also significantly decreased the Ang II- or 15% FBS-induced VSMC proliferation by inhibiting the expression of cell cycle associated proteins, such as p-Rb, cyclin D, and cyclin E. Compound C, a specific inhibitor of AMPK, or AMPK siRNA blocked the losartan-induced inhibition of cell proliferation and the $G_0/G_1$ cell cycle arrest. These data suggest that losartan-induced AMPK activation might attenuate Ang II-induced VSMC proliferation through the inhibition of cell cycle progression.

• BMB Reports
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• v.42 no.2
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• pp.113-118
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• 2009

Despite the growing body of evidence suggesting a role for MsrA in antioxidant defense, little is currently known regarding the function of MsrB in cellular protection against oxidative stress. In this study, we overexpressed the mammalian MsrB and MsrA genes in Saccharomyces cerevisiae and assessed their subcellular localization and antioxidant functions. We found that the mitochondrial MsrB3 protein (MsrB3B) was localized to the cytosol, but not to the mitochondria, of the yeast cells. The mitochondrial MsrB2 protein was detected in the mitochondria and, to a lesser extent, the cytosol of the yeast cells. In this study, we report the first evidence that MsrB3 overexpression in yeast cells protected them against $H_2O_2$-mediated cell death. Additionally, MsrB2 overexpression also provided yeast cells with resistance to oxidative stress, as did MsrA overexpression. Our results show that mammalian MsrB and MsrA proteins perform crucial functions in protection against oxidative stress in lower eukaryotic yeast cells.

• The Korean Journal of Physiology
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• v.23 no.1
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• pp.51-66
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• 1989

Mammalian cardiocytes secrete atrial natriuretic peptides (ANPs) into plasma, which cause marked natriuresis, diuresis, vasorelaxation and inhibition of hormone secretions. Aging influences the ability of the kidney both to conserve and to excrete sodium; i.e., in old animals, the excretory capacity of sodium is reduced and the time required to excrete sodium load is prolonged. Therefore, it is possible that animals differing in ages may respond differently to ANP. In the present study, we determined whether the renal, hormonal and vascular effects of ANP may be influenced by aging in conscious rabbits. The plasma renin concentration decreased with aging but plasma ANP concentration was significantly lower only in 24-month-old rabbits. Plasma aldosterone concentration and atrial ANP content did not change by aging. In 1-month-old rabbits, ANP (atriopeptin III, 3 ug/kg) administered intravenously caused hypotension and decreased in plasma renin and aldosterone concentrations, but did not cause diuresis and natriuresis. In 2 to 5 month-old rabbits, ANP caused hypotension, decreases in Plasma renin and aldosterone concentrations and marked renal effects. However, in 24-month-old rabbits, all the above effects of ANP was blunted. With hydration of physiological saline at a rate of 15 ml/kg/h for 2hr, urine volume and glomerular filtration rate did not change but the electrolyte excretion as well as fractional excretion of sodium significantly increased. The plasma concentrations of active renin and aldosterone were decreased but plasma inactive renin and ANP concentrations were increased. The changes in renal function and plasma level of hormone showed no differences in different ages. These results suggest that the peripheral vascular receptors to ANP may develop earlier than those in the kidney, and the attenuated vascular and renal responses to ANP in the old age may be due to age-related modifications in renal function and blood vessel.

• Proceedings of the KIEE Conference
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• 2007.04a
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• pp.67-69
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• 2007

Recently, the prevalence rate of diabetes in Korea has been increasing rapidly due to high growth of economy and changes in dietary lifestyle. Vascular complication is one of diabetic complications which have frequently occurred by obesity, hyperglycemia and impaired glucose metabolism. Photoplethysmogram(PPG) measured from finger and toe is very useful for evaluation of vascular aging and sclerosis level since the PPG signal represents characteristics of peripheral vascular. Several researchers have reported that second derivative of the finger PPG waveform was useful to evaluate vascular compliance and developed various analysis methods for vascular compliance. However, peripheral vascular compliance study for diabetic patient was never evaluated by using second derivative of PPG. Therefore, we aimed to objectively compare and to assess normal and diabetic group vascular compliance using the second derivative of PPG waveform in this study. The evaluated factors of second derivative of PPG are 'a', 'b', 'c', 'd', 'e' and b/a represents vascular compliance. Study found out that when vascular compliance is decreased, b/a is increased, the absolute value of b/a is decreased. The average vascular compliance of 50 diabetic patients with neuropathy is statistically lower than the normal group(p<0.05). We suggest an objective evaluation of peripheral vascular compliance for diabetic patients and prevention of vascular complication.

• Proceedings of the KIEE Conference
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• 2006.04a
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• pp.42-44
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• 2006

Up to the present, finger replantation patients have complained about various symptoms because of blood circulatory failure. Objective evaluation methods for the level of the blood circulatory failures in fingers were needed other than patient's subjective symptoms and complaints. Photoplethysmogram(PPG) measured from fingers is very useful for evaluation of vascular aging and sclerosis level since the PPG signal represents characteristics of peripheral vascular. Several researchers have reported that second derivative of the finger PPG waveform was useful to evaluate vascular compliance and developed various analysis methods for vascular compliance. However, vascular compliance study for finger replantation patient was never evaluated by using second derivative of PPG. Therefore, we aimed to objectively compare and to assess normal and replanted finger vascular compliance using the second derivative of PPG waveform in this study. The evaluated factors of second derivative of PPG are 'a', 'b', 'c', 'd', 'e' and b/a represents vascular compliance. Study found out that when vascular compliance is decreased, b/a is increased, the absolute value of b/a is decreased. For 43 finger replantation patients, the average vascular compliance of replanted finger is lower than the normal finger statistically(p=0.001). we suggested an objective evaluation of finger vascular compliance for finger replantation patients and effect of surgical operation.

• Journal of Acupuncture Research
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• v.19 no.3
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• pp.126-137
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• 2002

Objective : There is accumulating data that cardiovascular diseases, including hypertension, cerebro-vascular accident, coronary heart disease, relate to atherosclerotic changes. Increased serum levels of lipids could play a role in these circumstances. the SDPTG(the second derivative of photoplethysmogram waveform) is noninvasive methods for evaluating the pulse wave and is correlated with age and other risk factors for atherosclerosis. Methods : To study the effects of serum lipid levels on the SDPTG in the middle-age adults, data on serum lipid levels and the SDPTG were collected in 80 healthy middle age with varying serum lipid concentrations. Biological vascular age was assessed using the SDPTG. the SDPTG consists of an a, b, c, and d wave in systole and an e wave in diastole; an SDPTG aging index(Al) was calculated as (b-c-d-e)/a. Results : Serum triglyceride, total cholesterol, total lipid, phospholipid, HDL cholesterol levels were respectively and significantly correlated with SDPTG Al. Serum lipid levels and blood pressure are age-dependent and the SDPTG is blood pressure-dependent. Restricting analysis to age and blood pressure yield strong positive correlations between serum triglyceride, total lipid levels and SDPTG Al, but no correlations between serum total cholesterol, phospholipid levels and SDPTG Al. Conclusion : The results of this study suggest that preventive acupuncture programs or herbal medications for reducing serum lipid, especially triglyceride, levels in middle-age should include a evaluation of biological vascular aging with the second derivative of photoplethysmogram waveform.