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( Sun-uk Bak ),( Suji Kim ),( Hae-jun Hwang ),( Jung-a Yun ),( Wan-sung Kim ),( Moo-ho Won ),( Ji-yoon Kim ),( Kwon-soo Ha ),( Young-guen Kwon ),( Young-myeong Kim ) 생화학분자생물학회(구 한국생화학분자생물학회) 2017 BMB Reports Vol.50 No.2
Heme oxygenase (HO-1) catalyzes heme to carbon monoxide (CO), biliverdin/bilirubin, and iron and is known to prevent the pathogenesis of several human diseases. We assessed the beneficial effect of heme degradation products on osteoclastogenesis induced by receptor activator of NF-κB ligand (RANKL). Treatment of RAW264.7 cells with CORM-2 (a CO donor) and bilirubin, but not with iron, decreased RANKLinduced osteoclastogenesis, with CORM-2 having a more potent anti-osteogenic effect. CORM-2 also inhibited RANKLinduced osteoclastogenesis and osteoclastic resorption activity in marrow-derived macrophages. Treatment with hemin, a HO-1 inducer, strongly inhibited RANKL-induced osteoclastogenesis in wild-type macrophages, but was ineffective in HO-1<sup>+/- </sup>cells. CORM-2 reduced RANKL-induced NFATc1 expression by inhibiting IKK-dependent NF-κB activation and reactive oxygen species production. These results suggest that CO potently inhibits RANKL-induced osteoclastogenesis by inhibiting redox-sensitive NF-κB-mediated NFATc1 expression. Our findings indicate that HO-1/CO can act as an antiresorption agent and reduce bone loss by blocking osteoclast differentiation. [BMB Reports 2017; 50(2): 103-108]
Choi, Seunghwan,Kim, Joohwan,Kim, Ji-Hee,Lee, Dong-Keon,Park, Wonjin,Park, Minsik,Kim, Suji,Hwang, Jong Yun,Won, Moo-Ho,Choi, Yoon Kyung,Ryoo, Sungwoo,Ha, Kwon-Soo,Kwon, Young-Guen,Kim, Young-Myeong Nature Publishing Group 2017 Experimental and molecular medicine Vol.49 No.11
<P>Heme oxygenase-1-derived carbon monoxide prevents inflammatory vascular disorders. To date, there is no clear evidence that HO-1/CO prevents endothelial dysfunction associated with the downregulation of endothelial NO synthesis in human endothelial cells stimulated with TNF-α. Here, we found that the CO-releasing compound CORM-2 prevented TNF-α-mediated decreases in eNOS expression and NO/cGMP production, without affecting eNOS promoter activity, by maintaining the functional activity of the <I>eNOS</I> mRNA 3′-untranslated region. By contrast, CORM-2 inhibited MIR155HG expression and miR-155-5p biogenesis in TNF-α-stimulated endothelial cells, resulting in recovery of the 3′-UTR activity of <I>eNOS</I> mRNA, a target of miR-155-5p. The beneficial effect of CORM-2 was blocked by an NF-κB inhibitor, a miR-155-5p mimic, a HO-1 inhibitor and siRNA against HO-1, indicating that CO rescues TNF-α-induced eNOS downregulation through NF-κB-responsive miR-155-5p expression via HO-1 induction; similar protective effects of ectopic HO-1 expression and bilirubin were observed in endothelial cells treated with TNF-α. Moreover, heme degradation products, except iron and <I>N</I>-acetylcysteine prevented H<SUB>2</SUB>O<SUB>2</SUB>-mediated miR-155-5p biogenesis and eNOS downregulation. These data demonstrate that CO prevents TNF-α-mediated eNOS downregulation by inhibiting redox-sensitive miR-155-5p biogenesis through a positive forward circuit between CO and HO-1 induction. This circuit may play an important preventive role in inflammatory endothelial dysfunction associated with human vascular diseases.</P>
Tae-Hoon Kim,Ji-Yoon Kim,Jieun Bae,Young-Mi Kim,Moo-Ho Won,Kwon-Soo Ha,Young-Guen Kwon,Young-Myeong Kim 고려인삼학회 2021 Journal of Ginseng Research Vol.45 No.2
Background: Korean Red ginseng extract (KRGE) has beneficial effects on the cardiovascular system by improving endothelial cell function. However, its pharmacological effect on endothelial cell senescence has not been clearly elucidated. Therefore, we examined the effect and molecular mechanism of KRGE on the senescence of human umbilical vein endothelial cells (HUVECs). Methods: HUVECs were grown in normal or KRGE-supplemented medium. Furthermore, they were transfected with heme oxygenase-1 (HO-1) gene or treated with its inhibitor, a NF-κB inhibitor, and a miR-155-5p mimic or inhibitor. Senescence-associated characteristics of endothelial cells were determined by biochemical and immunohistochemical analyses. Results: Treatment of HUVECs with KRGE resulted in delayed onset and progression of senescence-associated characteristics, such as increased lysosomal acidic β-galactosidase and decreased telomerase activity, angiogenic dysfunction, and abnormal cell morphology. KRGE preserved the levels of anti-senescent factors, such as eNOS-derived NO, MnSOD, and cyclins D and A: however, it decreased the levels of senescence-promoting factors, such as ROS, activated NF-κB, endothelial cell inflammation, and p21 expression. The beneficial effects of KRGE were due to the induction of HO-1 and the inhibition of NF-κB-dependent biogenesis of miR-155-5p that led to the downregulation of eNOS. Moreover, treatment with inhibitors of HO-1, NF-κB, and miR-155-5p abolished the anti-senescence effects of KRGE. Conclusion: KRGE delayed or prevented HUVEC senescence through a signaling cascade involving the induction of HO-1, the inhibition of NF-κB-dependent miR-155-5p biogenesis, and the maintenance of the eNOS/NO axis activity, suggesting that it may protect against vascular diseases associated with endothelial senescence.
참깨에서 추출한 Sesamin 섭취가 혈청 지질 농도에 미치는 영향
윤명호,신준한,김한수,탁승제,최병일 아주대학교 1997 아주의학 Vol.2 No.2
Objectives : High serum cholesterol is one of the major risk factors of coronary artery disease. We investigated the lipid-towering property and the side effects of sesamin, an unsaturated fatty add extracted from sesame oil, for the primary prevention of coronary artery disease. Methods : The 37 patients (20 mates and 17 females) with hyperlipidemia, ages ranging from 22 years to 70 years old (48±12), who did not have atherosderotic diseases except essential hypertension were given three capsules of sesamin once daily for 6 weeks. The lipid profile of the patients were examined before and after sesamin treatment, and the patients were grouped according to the presence or abscence of hypertension, smoking habit and obesity. Result : Compared with pretreatment, the total cholesterol level of sesamin treated group decreased significantly (254.2±29.6 versus 241.6 34.0 ㎎/dl, p< 0.05). The level of LDL-cholesterol (162.6±24.3 versus 156.6±32.8 ㎎/dl)HDL- cholesterol (47.5±10.0 versus 47.0±8.7 ㎎/dl) and triglyceride (196.5±95.4 versus 179.3±96.7 ㎎/dl) and the ratio of LDL/HDL- cholesterol (3.6±0.9 versus 3.4±0.9) were not significantly different. The effect of cholesterol lowering property of sesamin was predominant in hypertensive, non- smoking and obese group (P< 0.05 vs pretreatment). The laboratory tests including complete blood cell counts, serum transaminases, total protein, albumin, blood urea nitrogen, creatinine and blood glucose did not change significantly. Conclusion : The lipid lowering effect of sesamin was statistically significant on the total cholesterol particularly with obese, non-smoking and hypertensive patients. There was no significant side effect during sesamin administration. Therefore, three capsules of sesamin as a single daily dose were effective in lowering total cholesterol and safe to administer in patients with hyperlipidemia.
가막만에 출현하는 동물플랑크톤의 종조성과 계절별 출현 양상
서호영,이인태,윤양호,최상덕,이삼노,한명일,김병섭,강윤호,이우범 한국환경생물학회 2002 환경생물 : 환경생물학회지 Vol.20 No.2
가막만에 출현하는 동물플랑크톤을 계절별(2001년 4월, 7월, 9월, 12월)로 Norpac네트를 이용하여 수직 채집하였다. 우점적으로 출현한 분류군은 4월과 12월에 요각류, 7월에 요각류와 지각류,9월에 야광충이었다. 출현 개체수는 22~17,197indiv. m^-3으로 시·공간적으로 변동폭이 매우 컸다. 요각류의 우점종은 4월에 Euryte-mora pacifica, Acartio omorii, Cenfropages abdominalis, Colanus sinicus, 7월에 Lobidocera rofunda와 A. erythraea, 9월에 A. eryfhraea와 Paracalanus parvus s. l., 12월에 A. omorii와 E. pacifca로 주로 내만종으로 변하였다. 그러나, 9월에 외양종인 Eucalanus sp.와 Neo-calnus sp. 또한 다수 출현하였다. 이와 같은 출현 경향은 가막만이 폐쇄성 내만임에도 불구하고 동물플랑크톤의 분포 특성은 내만수 이외에 계절적으로 외만수의 영향을 강하게 받고 있음을 암시하고 있다. Zooplankton was sampled vertically with a Norpac net from Gamag Bay in April, July, September and December, 2001. Copepods were predominant in April and December, and cladocerans in July and Noctiluca scintillans in September, respectively. There are high spatio-temporal fluctuations in the abundance of zooplankton with a range of 22∼17,197 indiv./㎥. In the copepod community, neritic species, Eurytemora pacifica, Acartia omorii, Centropages abdominalis and Calanus sinicus were predominant in April; Labidocera rotunda and A. erythraea in July; A. erythraea and Paracalanus parvus s. l. in September; A. omorii and E. pacifica in December. However, oceanic species Eucalanus sp. and Neocalanus sp. were abundant in September. It indicates that although Gamag Bay is semi-closed, the distribution pattern of zooplankton is seasonally strongly affected by oceanic waters in addition to neritic ones.