Valuation of ecosystem services in the organic carbon of the Pinus densiflora forest at Mt. Namsan, Seoul Metropolitan City

Lee, Eung-Pill,Lee, Soo-In,Jeong, Heon-Mo,Han, Young-Sub,Lee, Seung-Yeon,Park, Jae-Hoon,Jang, Rae-Ha,Hong, Youg-Sik,Jung, Young-Ho,Kim, Eui-Joo,Lee, Sang-Hun,You, Young-Han The Ecological Society of Korea 2019 Journal of Ecology and Environment Vol.43 No.4

Background: Standing biomass, litter production, rate of litter decomposition, amount of litter on forest floor, and amount of soil organic carbon distribution were investigated from March 2016 to November 2018 in order to evaluate the ecosystem value through organic carbon distribution in the Pinus densiflora forest at Namsan, Seoul Metropolitan City. Results: The amount of organic carbon in the Pinus densiflora forest was 261.09 ton C ha^-1 during the research period, and fixed organic carbon in plant through net photosynthesis was 3.2 ton C ha^-1 year^-1. The organic carbon in plant was 62.77 ton C ha^-1 (24.04%), in litter on the forest floor was 3.65 ton C ha^-1 (1.40%), and in soil was 194.67 ton C ha^-1 (74.56%). The value of plant, litter on forest floor, and soil organic carbon distribution were each 6,277,000 won ha^-1, 365, 000 won ha^-1, and 19,467,000 won ha^-1. The value per ton of fixed organic carbon in plant through net photosynthesis was 320,000 won ha^-1 year^-1 and the value of ecosystem services stored in carbon in the Namsan forest ecosystem was about 26.1 million won ha^-1 for 3 years. Conclusions: The results of this study suggest that the pine forests of Namsan rapidly decompose leaves due to the high atmospheric temperature and accumulate a large amount of organic carbon in the soil to provide climate control regulatory service function.

갈대 생육지에서 질소 시비가 사초의 생육과 수량 및 사료가치에 미치는 영향

서성,박진길,김원호,김맹중,이상학,정종성,박형수,성하균,이종경,Seo, Sung,Park, Jin Gil,Kim, Won Ho,Kim, Meing Jooung,Lee, Sang Hak,Jung, Jong Sung,Park, Hyung Soo,Sung, Ha Guyn,Lee, Joung Kyong 한국초지조사료학회 2013 한국초지조사료학회지 Vol.33 No.2

본 연구는 질소(N) 시비가 부존 조사료자원인 갈대(Phragmites communis)의 생육과 수량 및 사료가치에 미치는 영향을 구명하고자 2012년에 충남 천안과 경기 안산지역에서 실시되었다. 천안 국립축산과학원 갈대 재배지에서는 N 무시비구, N 50 kg/ha구, N 100 kg구 등 3처리를 두고 4월 30일 시비, 6월 21일 수확하였으며, 안산 시화간척지 갈대 자생지에서는 N 무시비구, N 60 kg/ha구 등 2처리를 두고 5월 1일 시비, 8월 1일 수확하였다. 갈대의 초장과 엽색은 N 시비구에서, 그리고 N 시비수준이 높을 때 양호하였다. 건물률은 N 시비구에서 약간 낮아지는 경향으로 천안지역은 무시비구 39.8%, N 시비구 37.6%, 36.7%, 안산지역은 무시비구 39.4%, N 시비구 37.6%였다. 천안지역의 건물수량, 조단백질 수량 및 가소화 건물수량은 무시비구에서 ha당 각각 4,026 kg, 235 kg, 1,850 kg, N 50 kg 시비구는 각각 4,658 kg, 306 kg, 2,388 kg, N 100 kg 시비구는 각각 5,622 kg, 446 kg, 3,143 kg으로 유의적으로 증가하였으며 (p<0.05), 안산지역은 무시비구에서 각각 2,802 kg, 177 kg, 1,288 kg, N 60 kg 시비구는 각각 3,876 kg, 294 kg, 1,853 kg으로 유의적으로 증가하였다 (p<0.05). 천안지역의 조단백질 함량, 건물 소화율 및 상대사료가치 (RFV)는 무시비구에서 각각 5.85%, 45.96%, 64.0 (품질 5등급), N 50 kg 시비구는 각각 6.58%, 51.27%, 72.3 (5등급), N 100 kg 시비구는 각각 7.94%, 55.91%, 72.7 (5등급)로 높아졌으며, 안산지역도 무시비구에서 각각 6.30%, 45.98%, 70.2 (5등급), N 60 kg 시비구는 각각 7.59%, 47.80%, 78.3 (4등급)으로 높아지는 경향이었다. 이상의 결과를 종합하여 볼 때, 갈대 생육지는 시비가 가능한 조건이라면(하천변이나 강변 등 수질오염이 우려되는 지역이 아닌), ha당 N 60~100 kg을 생육기에 시용해 주는 것이 생산량과 사료가치를 크게 개선시켜줄 수 있어 바람직하였다. This study was carried out to investigate the effect of nitrogen (N) fertilization on the forage growth, production and quality of native reed (Phragmites communis) grasses. Field experiments were conducted in Cheonan and in Ansan, 2012. Treatments were control (no N fertilization), 50 kg/ha and 100 kg/ha in Cheonan plots (fertilization on April $30^{th}$, and harvest on June $21^{st}$). Treatments in Ansan plots were control (no N fertilization) and 60 kg/ha (fertilization on May first, and harvest on August first). Forage growth and leaf colors were improved in N fertilized plots. However, the drymatter (DM) percentage was slightly decreased with N fertilization. Forage yields, in terms of DM, crude protein (CP) and digestible DM (DDM), were significantly increased with N fertilization in both sites. In Cheonan, DM, CP and DDM yields per ha were 4,026 kg, 235 kg and 1,850 kg, respectively, in the control plot, and were 4,658 kg, 306 kg and 2,388 kg, respectively, in the N 50 kg plot, and 5,622 kg, 446 kg and 3,143 kg, respectively, in the N 100 kg plot. In Ansan, DM, CP and DDM yields per ha were 2,802 kg, 177 kg and 1,288 kg, respectively, in the control plot, and were 3,876 kg, 294 kg and 1,853 kg, respectively, in the N 60 kg plot. Forage quality in terms of CP content, in vitro DM digestibility (IVDMD) and relative feed value (RFV) were also increased with N fertilization in both sites. In Cheonan, the CP content, IVDMD and RFV were 5.85%, 45.96% and 64.5 (grade 5), respectively, in the control plot, 6.58%, 51.27% and 72.3 (grade 5), respectively, in the N 50 kg plot, and 7.94%, 55.91% and 72.7 (grade 5), respectively, in the N 100 kg plot. In Ansan, the CP content, IVDMD and RFV were 6.30%, 45.98% and 70.2 (grade 5), respectively, in the control plot, and 7.59%, 47.80% and 78.3 (grade 4), respectively, in the N 60 kg plot. In conclusion, N fertilization of 60~100 kg/ha was desirable for greater forage production, with a higher quality of native Phragmites communis achievable. This should only be applied if the fertilization area is not located at a riverside/streamside or in riparian land where there is a high risk of water pollution by fertilization.

Heme oxygenase-1 (HO-1)/carbon monoxide (CO) axis suppresses RANKL-induced osteoclastic differentiation by inhibiting redox-sensitive NF-κB activation

( 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^+/-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]

Current Status of Ginseng Cultivation and Soil Characteristics of Northeastern Three Provinces in China

Yang Ho Park,Jang Uk Kim,Dong Hwi Kim,Yeon Kyu Sonn,Jin Ha Yun,Huhn Pal Moon,Soo Yeon Cho 한국토양비료학회 2016 한국토양비료학회지 Vol.49 No.6

This study was conducted to improve the continuous techniques for international competitiveness of ginseng industry to Korea-China FTA negotiation and conclusion, and provide the basic information for ginseng industry development of Korea. It was carried out the visiting of the northeastern three provinces (Jilin, Liaoling and Heilongjang) in China for 3-year from 2014 to 2016 and observed the farmers’ fields of ginseng cultivation with soil environmental status. The types of ginseng cultivation could be observed in small scales of 0.5∼3.0 ha, in middle scales of 4.0∼10.0 ha and in large scales of 30∼700 ha with the kinds of imhasam, Chinese ginseng, Korean ginseng and western ginseng. Also ginseng was cultivated in newly reclaimed land of forest in two types of direct seeding and transplanting of ginseng seedlings. The field beds of ginseng growing were covered with vinyl films in arch design of 100∼130 cm height and vinyl was painted in spraying with blue, green and yellow colours for shading. It was investigated in status of the physico-chemical properties of soils. The physical information on the field soils were silt loam, loam and sandy loam in soil textures, and some plain in low slope, some alluvial fan or local valley in forest of land topography. Soil pH ranged within 5.0∼5.2, soil EC was 0.93∼3.78 dS m<SUP>-1</SUP>, organic matter was 37∼35 g kg<SUP>-1</SUP>, nitrate nitrogen 63∼490 mg kg<SUP>-1</SUP>, available P2O5 55∼163 mg kg-1, and in exchangeable cations, K was 0.30∼0.98, Ca was 6.5∼14.0, Mg was 1.1∼5.3 cmolc kg<SUP>-1</SUP> in ranges. Farmers used the fertilizer for ginseng cultivation in 10∼11 t of compost, 200∼400 kg ha<SUP>-</SUP>1 of complex fertilizer and 750 kg ha<SUP>-1</SUP> of oil cakes. The northeastern three provinces of China can use the newly lands with large areas of ginseng cultivation in soil sickness by continuous cropping. and the soil basic fertility is batter than that of Korean in standard guide of ginseng cultivation soil.

Current Status of Ginseng Cultivation and Soil Characteristics of Northeastern Three Provinces in China

Park, Yang Ho,Kim, Jang Uk,Kim, Dong Hwi,Sonn, Yeon Kyu,Yun, Jin Ha,Moon, Huhn Pal,Cho, Soo Yeon 한국토양비료학회 2016 한국토양비료학회지 Vol.49 No.6

This study was conducted to improve the continuous techniques for international competitiveness of ginseng industry to Korea-China FTA negotiation and conclusion, and provide the basic information for ginseng industry development of Korea. It was carried out the visiting of the northeastern three provinces (Jilin, Liaoling and Heilongjang) in China for 3-year from 2014 to 2016 and observed the farmers' fields of ginseng cultivation with soil environmental status. The types of ginseng cultivation could be observed in small scales of 0.5~3.0 ha, in middle scales of 4.0~10.0 ha and in large scales of 30~700 ha with the kinds of imhasam, Chinese ginseng, Korean ginseng and western ginseng. Also ginseng was cultivated in newly reclaimed land of forest in two types of direct seeding and transplanting of ginseng seedlings. The field beds of ginseng growing were covered with vinyl films in arch design of 100~130 cm height and vinyl was painted in spraying with blue, green and yellow colours for shading. It was investigated in status of the physico-chemical properties of soils. The physical information on the field soils were silt loam, loam and sandy loam in soil textures, and some plain in low slope, some alluvial fan or local valley in forest of land topography. Soil pH ranged within 5.0~5.2, soil EC was $0.93{\sim}3.78dS\;m^{-1}$, organic matter was $37{\sim}35g\;kg^{-1}$, nitrate nitrogen $63{\sim}490mg\;kg^{-1}$, available $P_2O_5$ $55{\sim}163mg\;kg^{-1}$, and in exchangeable cations, K was 0.30~0.98, Ca was 6.5~14.0, Mg was $1.1{\sim}5.3cmol_c\;kg^{-1}$ in ranges. Farmers used the fertilizer for ginseng cultivation in 10~11 t of compost, $200{\sim}400kg\;ha^{-1}$ of complex fertilizer and $750kg\;ha^{-1}$ of oil cakes. The northeastern three provinces of China can use the newly lands with large areas of ginseng cultivation in soil sickness by continuous cropping. and the soil basic fertility is batter than that of Korean in standard guide of ginseng cultivation soil.

정신분열병에 대한 리스페리돈의 효과 및 안정성

이민수,김용구,김영훈,연병길,오병훈,윤도준,윤진상,이철,정희연,강병조,김광수,김동언,김명정,김상훈,김희철,나철,노승호,민경준,박기창,박두병,백기청,백인호,손봉기,손진욱,양병환,양창국,우행원,이정호,이종범,이홍식,임기영,전태연,정영조,정영철,정인과,정인원,지익성,채정호,한상익,한선호,한진희,서광윤 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

연구목적 : 본 시험의 목적은 임상시험 시작전에 연구자들을 대상으로 PANSS Workshop을 통하여 PANSS, ESRS에 대한 국내에서의 표준화 작업을 구축하고 새로운 정신병 치료제인 리스페리돈의 효과와 안정성을 재확인하여 리스페리돈 사용에 대한 적정화를 이루는데 있다. 연구방법 : 1996년 4월부터 1996년 9월까지 국내 39개 대학병원 정신과에 입원중인 혹은 증상이 악화되어 입원하는 정신분열병 환자 377명을 대상으로 다시설 개방 연구를 시행하였다. 1주일간의 약물 배설기간을 가진후, 리스페리돈을 8주간 투여하였고, 기준점, 1주, 2주, 4주, 그리고 8주후에 평가되었다. 용량은 제1일에는 리스페리돈 1mg씩 1일 2회, 제2일에는 2mg씩 1일 2회, 제3∼7일에는 3mg씩 1일 2회 투여하였다. 이후 환자의 임상상태에 따라 임의로 증량할 수 있으며, 최대 일일 16mg을 초과하지 않도록 하였다. 추체외로 증상을 조절하기 위한 투약을 허용하였다. 임상증상 및 부작용의 평가는 PANSS(Positive and Negative Syndrome Scale), CGI(Clinical Global Impression) 그리고 ESRS(Extrapyramidal Symptom Rating Scale)을 사용하였다. 연구결과 : 377명중 343명(91%)이 8주간의 연구를 완결하였다. 치료 종결시점인 8주후 PANSS 총점수가 20% 이상 호전된 경우를 약물 반응군으로 정의할때, 약물반응군은 81.3%였다. 리스페리돈에 반응하는 예측인자로는 발병연령, 이전의 입원 횟수, 유병기간이 관련 있었다. 리스페리돈은 1주후부터 PANSS양성, 음성, 및 일반정신병리 점수상에 유의한 호전을 보여 효과가 빨랐다. CGI의 경우도 기준점에 비해 1주후부터 유의한 감소를 나타내었다. ESRS의 경우, 파킨슨 평가점수는 기준점과 비교해 투여 1주, 2주, 4주후 유의하게 증가되었다가 8주후 기준점과 차이가 없었다. Dystonia 평가점수는 1주후만 유의한 증가를 보였으며, dyskinesia 평가점수는 유의한 차이가 없었다. 혈압, 맥박수의 생명징후 및 일반 혈액학 검사, 생화학적 검사, 심전도 검사에서 유의한 변화는 없었다. 결 론 : 이상의 다시설 개방 임상 연구를 통해 리스페리돈은 정신분열병 환자에서 양성증상뿐만 아니라 음성증상 및 전반적인 증상에도 효과적인 것으로 사료된다. 보다 명확한 평가를 위해서는 다른 항정신병약물과의 이중맹검 연구가 필요할 것으로 생각되며, 또한 장기적 치료에 대한 평가도 함께 이루어져야 하겠다. Objective : The purpose of this study was to investigate the efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. Method : This multicenter open study included 377 schizophrenic patients drawn from 39 university hospitals. After a wash-out period of 1 week, the schizophrenic patients were treated with risperidone for 8 weeks and evaluated at 5 points ; at baseline, and 1, 2, 4 and 8 weeks of treatment. The dose was increased from 2mg/day(1mg twice daily) to 6mg/day(3mg twice daily) during the first week and adjusted to a maximum of 16mg/day over the next 7 weeks according to the patient's clinical response. Medication to control extrapyramidal symptoms was permitted. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. Results : 343(91%) of 377 patients completed the 8-week trial period. Clinical improvement, as defined by a 20% or more reduction in total PANSS score at end point, was shown by 81.3% of patients. The predictors of response to risperidone were associated older age, shorter duration of illness, fewer previous hospitalization. Risperidone had rapid onset of action ; a significant decrease of the total PANSS and three PANSS factor(positive, negative, general), and CGI was already noticed at the end of first week. For the ESRS, parkinsonism rating scores were significantly increased until week 4 comparing with baseline. Dystonia rating scores were significantly increased until week 1, and dyskinesia rating scores were not significantly changed during the study. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial. Conclusions : This study suggests that risperidone is generally safe and effective against both the positive and negative symptoms in our group of patients.

2010 파주, 안산지역 갈대, 억새 등 야초류의 이용실태와 사료가치 평가

서성(Sung Seo),김원호(Won Ho Kim),정민웅(Min Woong Jung),박형수(Hyung Soo Park),심재진(Jae Jin Shim),박진길(Jin Gil Park),성하균(Ha Guyn Sung),김종덕(Jong Duk Kim),이종경(Joung Kyong Lee) 한국초지조사료학회 2011 한국초지조사료학회지 Vol.31 No.2

본 연구는 부존 조사료자원의 이용을 활성화하여 수입사료를 줄이고 가축 사료비를 절감하고자 2010년도에 경기 파주 (민통선 지역)와 경기 안산 (시화지구)에서 갈대와 억새 등 야초자생지를 탐색하고, 수확?이용실태 조사와 함께 사료가치를 분석하였다. 파주 민통선 내억새 (Miscanthus sinensis)와 갈대 (Phragmites communis) 혼합 자생지는 90~100 ㏊ 규모로, 1차 곤포작업으로 사일리지 520톤 (㏊당 6톤), 2차로 380톤 (㏊당 4톤)을 조제하여, 연 사일리지 900톤 (㏊당 10톤)을 생산하였다. 곤포의 유통가격은 롤당 52~55천 원으로 ㎏당 130~137.5원이었다. 곤포는 자가소비 50~70%, 판매유통 30~50%로, 수익성은 인건비 정도로 추정되었다. 초장 70 ㎝의 재생 억새는 조단백질 9.6%, 상대사료가치 82.4 (건초 4등급), 건물 소화율 67.7%, 초장 70 ㎝의 재생 갈대는 각각 13.8%, 84.3 (4등급), 67.9%로 사료가치는 높았으며, 수확이 늦어짐에 따라 사료가치는 크게 낮아졌다. 안산 시화지구 (3공구)의 갈대 등 야초류자생지는 100 ㏊ 정도로 2009년도에는 50 ㏊에서 사일리지 550톤 (㏊당 11톤)을 생산하여 롤당 50천 원에 유통하였으며, 2010년도는 잦은 강우와 장마로 부분 이용에 그쳤다. 고초기의 갈대는 건물률 89.8%, 조단백질 2.2%, NDF 80.6%, ADF 55.4%, 상대사료가치 52.9 (5등급), 건물 소화율 36.4%로 볏짚에 비해서도 사료가치는 크게 낮았다. 초장 80 ㎝의 재생 갈대는 조단백질 12.9%, 상대사료가치 99.8 (3등급), 건물 소화율 66.6%로 사료가치는 양호하였으며, 개화기의 초장 150 ㎝ 갈대는 조단백질 4.5%, 상대사료가치 59.9 (5등급), 건물 소화율 42.2%로 볏짚의 사료가치와 비슷하였다. 이상의 결과를 종합하여볼 때, 갈대, 억새 등 야초류는 현 상태에서 최대한 수거?이용하되, 사료가치를 유지하고 가축 기호성을 고려한 시기에 수확하는 것이 중요하며, 최소한 볏짚과 비슷하거나 그 이상의 사료가치를 기대하기 위해서는 7월 중순 이전 (늦어도 7월까지)에 수확?이용하는 것이 권장된다. 본 연구에서 조사된 대부분의 야초류는 상대사료가치가 75 이하인 건초 5등급으로 사료가치는 매우 낮았으며, 키가 작은 영양생장기에 수확한 경우에만 4등급으로 나타났다. 부존 조사료자원의 이용은 양질의 사료작물 생산과 병행하여 추진하는 것이 바람직하였다. This study was carried out in 2010 to investigate the utilization and nutritive value of native grasses, such as Phragmites communis and Miscanthus sinensis which might reduce the cost of feeding domestic cattle. The regions within the Civilian Control Line in Paju and Sihwa region in Ansan were surveyed. In Paju, the yearly silage production was 900 MT harvested from 90 ha (10 MT/㏊). About 30~50% of these were sold out at the marketing price of 52,000~55,000 Won per roll (130~137.5 Won/㎏). Regrown Miscanthus sinensis of 70 ㎝ in length contained 9.6% of crude protein (CP), 82.4 of relative feed value (RFV), and 67.7% of in vitro dry matter digestibility (IVDMD). Regrown Phragmites communis of 70 ㎝ in length contained 13.8% of CP, 84.3 of RFV, and 67.9% of IVDMD. As harvesting was delayed, the quality was decreased dramatically. In Ansan region, Phragmites communis plantation covers 100 ha. The silage production was 550 MT from the area of 50 ha (11 MT/㏊) in 2009. And the marketing price was 50,000 Won per roll. But in 2010 only a small amount of grasses could have been baled due to frequent and much rainfall from spring to summer season. However, the good forage quality was observed from regrown Phragmites communis of 80 ㎝ in length, 12.9% CP, 99.8 RFV and 66.6% IVDMD, while that of late matured grasses was very low, 2.2% CP, 52.9 RFV and 36.4% IVDMD, greatly lower than forage quality of rice straw. The quality of grasses at bloom stage of 150 ㎝ in length was similar to that of rice straw, showing 4.5% CP, 59.9 RFV and 42.2% IVDMD. In conclusion, the overall quality of most native grasses in this survey were very poor. Therefore, we recommend that Phragmites communis and Miscanthus sinensis should be harvested during June or July to obtain better forage quality which is richer in forage values than rice straw. Production of high quality forage crops was also desirable for self sufficiency of forage.

Korean Red ginseng prevents endothelial senescence by downregulating the HO-1/NF-κB/miRNA-155-5p/eNOS pathway

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.

Carbon monoxide prevents TNF-α-induced eNOS downregulation by inhibiting NF-κB-responsive miR-155-5p biogenesis

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>

Hypoxia-Responsive MicroRNA-101 Promotes Angiogenesis <i>via</i> Heme Oxygenase-1/Vascular Endothelial Growth Factor Axis by Targeting Cullin 3

Kim, Ji-Hee,Lee, Kwang-Soon,Lee, Dong-Keon,Kim, Joohwan,Kwak, Su-Nam,Ha, Kwon-Soo,Choe, Jongseon,Won, Moo-Ho,Cho, Byung-Ryul,Jeoung, Dooil,Lee, Hansoo,Kwon, Young-Guen,Kim, Young-Myeong Mary Ann Liebert 2014 Antioxidants & redox signaling Vol.21 No.18

<P>Aims: Hypoxia induces expression of various genes and microRNAs (miRs) that regulate angiogenesis and vascular function. In this study, we investigated a new functional role of new hypoxia-responsive miR-101 in angiogenesis and its underlying mechanism for regulating heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) expression. Results: We found that hypoxia induced miR-101, which binds to the 3 ' untranslated region of cullin 3 (Cul3) and stabilizes nuclear factor erythroid-derived 2-related factor 2 (Nrf2) via inhibition of the proteasomal degradation pathway. miR-101 overexpression promoted Nrf2 nuclear accumulation, which was accompanied with increases in HO-1 induction, VEGF expression, and endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) production. The elevated NO-induced S-nitrosylation of Kelch-like ECH-associated protein 1 and subsequent induction of Nrf2-dependent HO-1 lead to further elevation of VEGF production via a positive feedback loop between the Nrf2/HO-1 and VEGF/eNOS axes. Moreover, miR-101 promoted angiogenic signals and angiogenesis both in vitro and in vivo, and these events were attenuated by inhibiting the biological activity of HO-1, VEGF, or eNOS. Moreover, these effects were also observed in aortic rings from HO-1(+/-) and eNOS(-/-) mice. Local overexpression of miR-101 improved therapeutic angiogenesis and perfusion recovery in the ischemic mouse hindlimb, whereas antagomiR-101 diminished regional blood flow. Innovation: Hypoxia-responsive miR-101 stimulates angiogenesis by activating the HO-1/VEGF/eNOS axis via Cul3 targeting. Thus, miR-101 is a novel angiomir. Conclusion: Our results provide new mechanistic insights into a functional role of miR-101 as a potential therapeutic target in angiogenesis and vascular remodeling. Antioxid. Redox Signal. 21, 2469-2482.</P>