What is the Key Step in Muscle Fatty Acid Oxidation after Change of Plasma Free Fatty Acids Level in Rats?

도경오,서상두,김종연 대한약리학회 2005 The Korean Journal of Physiology & Pharmacology Vol.9 No.3

The purpose of this study was to discern the critical point in skeletal muscle fatty acid oxidation by changing plasma free fatty acids (FFA) level in rat. In the study, 3 key steps in lipid oxidation were examined after changing plasma FFA level by acipimox. The rates of both palmitate and palmitoyl- carnitine oxidation were decreased by decrease of plasma FFA level, however, carnitine palmitoyl transferase (CPT) 1 activity was not changed, suggesting CPT1 activity may not be involved in the fatty acid oxidation at the early phase of plasma FFA change. In the fasted rats, β-hydroxy acyl-CoA dehydrogenase (β-HAD) activity was depressed to a similar extent as palmitate oxidation by a decrease of plasma FFA level. This suggested that β-oxidation might be an important process to regulate fatty acid oxidation at the early period of plasma FFA change. Citrate synthase activity was not altered by the change of plasma FFA level. In conclusion, the critical step in fatty acids oxidation of skeletal muscles by the change of plasma FFA level by acipimox in fasting rats might be the β-oxidation step rather than CPT1 and TCA cycle pathways.

Effects of TGF-β1 Ribbon Antisense on CCl₄-induced

도경오 대한약리학회 2008 The Korean Journal of Physiology & Pharmacology Vol.12 No.1

Ribbon-type antisense oligonucleotide to TGF-β1 (TGF-β1 RiAS) was designed and tested to prevent or resolve the fibrotic changes induced by CCl₄ injection. When Hepa1c1c7 cells were transfected with TGF-β1 RiAS, the level of TGF-β1 mRNA was effectively reduced. TGF-β1 RiAS, mismatched RiAS, and normal saline were each injected to mice via tail veins. When examined for the biochemical effects on the liver, TGF-β1 mRNA levels were significantly reduced only in the TGF-β1 RiAS-treated group. The results of immunohistochemical studies showed that TGF-β1 RiAS prevented the accumulation of collagen and α-smooth muscle actin, but could not resolve established fibrosis. These results indicate that ribbon antisense to TGF-β1 with efficient uptake can effectively prevent fibrosis of the liver. Ribbon-type antisense oligonucleotide to TGF-β1 (TGF-β1 RiAS) was designed and tested to prevent or resolve the fibrotic changes induced by CCl₄ injection. When Hepa1c1c7 cells were transfected with TGF-β1 RiAS, the level of TGF-β1 mRNA was effectively reduced. TGF-β1 RiAS, mismatched RiAS, and normal saline were each injected to mice via tail veins. When examined for the biochemical effects on the liver, TGF-β1 mRNA levels were significantly reduced only in the TGF-β1 RiAS-treated group. The results of immunohistochemical studies showed that TGF-β1 RiAS prevented the accumulation of collagen and α-smooth muscle actin, but could not resolve established fibrosis. These results indicate that ribbon antisense to TGF-β1 with efficient uptake can effectively prevent fibrosis of the liver.

Insulin Resistance of Skeletal Muscle was Recovered by Leptin Injection in vivo, but not in vitro, in High-fat Diet Fed Rats

도경오,박정옥,전정례,김종연 대한약리학회 2005 The Korean Journal of Physiology & Pharmacology Vol.9 No.2

We examined the effect of leptin on the insulin resistance in skeletal muscles by measuring the glucose transport. Male Wistar rats were fed with chow or high-fat diets for 30 days. Three days before sacrifice, high-fat fed rats were subcutaneously injected with leptin (1 mg/kg body weight) for 3 days. The glucose transports in the epitrochlearis and soleus muscle were not different among the experimental groups under basal state, however these were decreased significantly in the high fat-diet rats under insulin-stimulation (p<0.01). Leptin treatment recovered the decreased glucose transport in the epitrochlearis (p<0.05) and soleus (p=0.08). Triglyceride concentration in the soleus muscle was increased significantly in the high fat-fed rats, compared to chow diet rats (p<0.01), and it was decreased significantly by leptin treatment (p<0.01). The glucose transport was measured under basal and 60μU/ml of insulin with or without 50 ng/ml of leptin. Leptin had no direct stimulatory effect on glucose transport under both basal and insulin-stimulated conditions in vitro. These results demonstrate that leptin injection to high fat diet fed rats recovered impaired insulin responsiveness of the skeletal muscles and muscle triglyceride concentration. However, there was no direct stimulatory effect of leptin on insulin sensitivity of the skeletal muscle in vitro.

장환형 (Large-circular) 안티센스를 이용한 난소암세포 성장 관련 유전자의 발굴

도경오 ( Kyung Oh Doh ),천근수 ( Geun Soo Chun ),심재철 ( Jae Chul Sim ),양회생 ( Hoe Saeng Yang ) 대한산부인과학회 2009 Obstetrics & Gynecology Science Vol.52 No.7

목적: 난소암의 성장에 관련된 새로운 치료목표 유전자의 발굴을 시도하였다. 연구 방법: 재조합 M13 파아지에서 유래한 단일가닥 장환형 (large-circular, LC) 안티센스 DNA를 이용하여 난소암의 성장에 관련된 유전자를 발굴하기 위해 240개의 유전자가 클로닝 된 플라스미드를 대장균에서 배양한 후 단일가닥 장환형 안티센스 DNA를 생산하였다. 생산된 장환형 안티센스를 난소암 세포주에 주입하여 각각의 유전자의 발현과 이것이 암세포의 성장을 저해하는지를 현미경과 MTT 정량으로 관찰하였다. 결과: 240개 유전자의 발현을 억제한 결과 17개의 유전자가 암세포의 성장과 관련이 있는 것으로 밝혀졌다. 이 중에는 CD44, EpCAM 등 암세포의 성장과 관련된 것으로 알려진 유전자도 있었고 이 연구를 통해 새롭게 발굴된 것들도 있었다. 결론: 다량의 안티센스를 이용하여 유효한 난소암 치료 표적을 발굴하였고 이들에 대한 더욱 자세한 연구로 새로운 항암목표물을 개발할 수 있을 것으로 기대된다. Objective: The aim of this study is to find out the genes which are related to ovarian cancer cell growth using large circular antisense library. Methods: Clones for antisense library were uni-directionally sub-cloned into pBS SK (-) vector. LC-antisense molecules were then purified from the culture supernatants of the bacterial competent cells superinfected with M13K07 helper bacteriophages. The LC-antisense library to 240 unigene clone was constructed and utilized in the identification of genes functionally involved in the growth of ovarian cancer cells. Results: The 17 numbers out of the 240 numbers of the antisense library exerted a marked inhibitory effect on the growth of SK-OV 3. Conclusion: The putative functional categorization of each gene was then conducted via public databases. These candidates may be used as target genes for drug development or adjuvant of conventional chemotherapeutic drugs.

항산화제가 고압산소에 의한 뇌독성에 미치는 영향

도경오 ( Doh Kyung-oh ),성훈기 ( Sung Hoon-ki ) 국군의무사령부 2004 대한군진의학학술지 Vol.35 No.1

씨름선수에서 체중 감량과 회복기의 Leptin과 PAI-1 변화

김용운,도경오,권태동,박덕일,장응찬,박소영,김종연,이석강 대한스포츠의학회 2000 대한스포츠의학회지 Vol.18 No.2

Obesity which is defined as accumulation of excess body fat, is central factor of insulin resistance syndrome. Recently, it is revealed tat adipose tissue is not simply an energy storage organ but it also secretes a variety of molecules which affect the metabolism of the whole body, those are leptin and plasminogen activator inhibitor-1(PAI-1). Therefore, leptin and PAI-1 are increased in the obese state. Leptin regulates energy homeostasis and satiety and PAI-1 regulates fibrinolytic system. For these reasons, elevated levels of leptin and PAI-1 are considered as link factors between obesity and insulin resistance syndrome. However, the exact regulating mechanism for serum levels of leptin and PAI-1 is not fully understood yet. In this study, to evaluate the regulating mechanisms of serum levels of leptin and PAI-1 according to the weight changes, we measured leptin, PAI-1, physical, metabolic, and endocrine parameters during 10 days of weight reduction and 10 days of regain period in 7 young athletes. The mean body weight change was -4.7 kg(5.0%) in the weight reduction period and -2.4 kg(2.5%) in the weight regain period compared to baseline value. Baseline level of leptin in athletes was 1.7±0.66 ng/ml, which was significantly correlated with body weight, BMI, percent body fat, body fat mass, triglyceride, insulin, and PAI-1. Baseline level of PAI-1 in athletes was 16.6±5.26 ng/ml, which was significantly correlated with body weight, BMI, triglyceride, insulin, and leptin. Leptin was decreased to 0.7±0.39(44% of the basaline value) in the weight reduction period, and increased to 1.9±0.64(119% of the baseline value) in the regain period. PAI-1 was decreased to 7.4±2.72(44% of the basaline value) in the weight reduction period, and increased to 22.8±7.33(138% of the baseline value) in the regain period. The changes of leptin during weight reduction period were significantly correlated with the changes of insulin(r=0.890, P<0.01) and triglycerides(r=0.874, P<0.01). The changes of PAI-1 during weight reduction period were significantly correlated with the changes of FFA(r=0.889, P<0.01) and triglycerides(r=0.869, P<0.05). The changes of both leptin and AAI-1 during weight regain period were significantly correlated with the changes of insulin(r=0.755 and 0.849, P<0.05, respectively). In summary, these results suggest that serum levels of leptin and PAI-1 were affected by weight cycling, the percentages of change were more greater than that of weight change, and rebound phenomena were occurred during weight regain period.

발효, 세포배양, 생물공정 저독성의 새로운 양이온성 리포좀을 이용한 유전자의 전달

강현구 ( Hyun Gu Kang ),도경오 ( Kyung Oh Doh ),서영배 ( Young Bae Seu ) 한국미생물생명공학회 2006 한국미생물·생명공학회지 Vol.34 No.4

장환형 안티센스 Library를 이용한 간암세포 성장 관련 유전자의 발굴

서정일,김강,박윤선,도경오 대한간학회 2008 Clinical and Molecular Hepatology(대한간학회지) Vol.14 No.3(S)

해군장병에서 비만에 관한 연구

성훈기 ( Hoon-ki Sung ),도경오 ( Kyung-oh Doh ) 국군의무사령부 2004 대한군진의학학술지 Vol.35 No.1

Effect of Exercise Intensity on Unfolded Protein Response in Skeletal Muscle of Rat

김기훈,김은혜,이성혜,전만중,박소영,도경오 대한약리학회 2014 The Korean Journal of Physiology & Pharmacology Vol.18 No.3

Endoplasmic reticulum (ER) stress, unfolded protein response (UPR), and mitochondrial biogenesiswere assessed following varying intensities of exercise training. The animals were randomly assignedto receive either low- (LIT, n=7) or high intensity training (HIT, n=7), or were assigned to a controlgroup (n=7). Over 5 weeks, the animals in the LIT were exercised on a treadmill with a 10° inclinefor 60 min at a speed of 20 m/min group, and in the HIT group at a speed of 34 m/min for 5 daysa week. No statistically significant differences were found in the body weight, plasma triglyceride,and total cholesterol levels across the three groups, but fasting glucose and insulin levels weresignificantly lower in the exercise-trained groups. Additionally, no statistically significant differenceswere observed in the levels of PERK phosphorylation in skeletal muscles between the three groups. However, compared to the control and LIT groups, the level of BiP was lower in the HIT group. Compared to the control group, the levels of ATF4 in skeletal muscles and CHOP were significantlylower in the HIT group. The HIT group also showed increased PGC-1α mRNA expression incomparison with the control group. Furthermore, both of the trained groups showed higher levels ofmitochondrial UCP3 than the control group. In summary, we found that a 5-week high-intensityexercise training routine resulted in increased mitochondrial biogenesis and decreased ER stress andapoptotic signaling in the skeletal muscle tissue of rats.