DJ-1 protects cell death from a mitochondrial oxidative stress due to GBA1 deficiency

Nam Younwoo,Na Jiyeon,Ma Shi-Xun,Park Ha-Eun,Park Hyeonwoo,Lee Eunmin,Kim Hyerynn,Jang Sang-Min,Ko Han Seok,Kim Sangjune 한국유전학회 2024 Genes & Genomics Vol.46 No.5

Background GBA1 mutations are the most common genetic risk factor for development of Parkinson’s disease (PD). The loss of catalytic activity in GBA1, as well as the reduction of the GBA1 protein in certain cellular compartment, may increase disease progression. However, the mechanisms underlying cellular dysfunction caused by GBA1 deficiency are still mostly unknown. Objective In this study, we focus on the genetic interaction between GBA1 deficiency and PD-causing genes, such as DJ-1, in mitochondrial dysfunction. Methods GBA1 knockout (KO) SH-SY5Y cells were used to assess DJ-1 functions against oxidative stress in vitro. The levels of cellular reactive oxygen species were monitored with MitoSOX reagent. The expression of the PARK7 gene was analyzed using the quantitative real-time PCR (qRT-PCR). To understand the mechanism underlying DJ-1 upregulation in GBA1 KO cells, we assess ROS levels, antioxidant protein, and cell viability in GBA1 KO cells with treatment of ROS inhibitor N-acetyl-cysteine or miglustat, which is an inhibitor of glucosylceramide synthase. Dopaminergic degeneration was assessed from Gba1 L444P heterozygous mice mated with Park7 knockout mice. Results We find that DJ-1 is significantly upregulated in GBA1 KO cells. Elevated levels of DJ-1 are attributed to the transcriptional expression of PARK7 mRNA, but not the inhibition of DJ-1 protein degradation. Because DJ-1 expression is highly linked to oxidative stress, we observe cellular reactive oxygen species (ROS) in GBA1 KO cells. Moreover, several antioxidant gene expressions and protein levels are increased in GBA1 KO cells. To this end, GBA1 KO cells are more susceptible to H2O2-induced cell death. Importantly, there is a significant reduction in dopaminergic neurons in the midbrain from Gba1 L444P heterozygous mice mated with Park7 knockout mice, followed by mild motor dysfunction. Conclusion Taken together, our results suggest that DJ-1 upregulation due to GBA1 deficiency has a protective role against oxidative stress. It may be supposed that mutations or malfunctions in the DJ-1 protein may have disadvantages in the survival of dopaminergic neurons in the brains of patients harboring GBA1 mutations. Background GBA1 mutations are the most common genetic risk factor for development of Parkinson’s disease (PD). The loss of catalytic activity in GBA1, as well as the reduction of the GBA1 protein in certain cellular compartment, may increase disease progression. However, the mechanisms underlying cellular dysfunction caused by GBA1 deficiency are still mostly unknown. Objective In this study, we focus on the genetic interaction between GBA1 deficiency and PD-causing genes, such as DJ-1, in mitochondrial dysfunction. Methods GBA1 knockout (KO) SH-SY5Y cells were used to assess DJ-1 functions against oxidative stress in vitro. The levels of cellular reactive oxygen species were monitored with MitoSOX reagent. The expression of the PARK7 gene was analyzed using the quantitative real-time PCR (qRT-PCR). To understand the mechanism underlying DJ-1 upregulation in GBA1 KO cells, we assess ROS levels, antioxidant protein, and cell viability in GBA1 KO cells with treatment of ROS inhibitor N-acetyl-cysteine or miglustat, which is an inhibitor of glucosylceramide synthase. Dopaminergic degeneration was assessed from Gba1 L444P heterozygous mice mated with Park7 knockout mice. Results We find that DJ-1 is significantly upregulated in GBA1 KO cells. Elevated levels of DJ-1 are attributed to the transcriptional expression of PARK7 mRNA, but not the inhibition of DJ-1 protein degradation. Because DJ-1 expression is highly linked to oxidative stress, we observe cellular reactive oxygen species (ROS) in GBA1 KO cells. Moreover, several antioxidant gene expressions and protein levels are increased in GBA1 KO cells. To this end, GBA1 KO cells are more susceptible to H2O2-induced cell death. Importantly, there is a significant reduction in dopaminergic neurons in the midbrain from Gba1 L444P heterozygous mice mated with Park7 knockout mice, followed by mild motor dysfunction. Conclusion Taken together, our results suggest that DJ-1 upregulation due to GBA1 deficiency has a protective role against oxidative stress. It may be supposed that mutations or malfunctions in the DJ-1 protein may have disadvantages in the survival of dopaminergic neurons in the brains of patients harboring GBA1 mutations.

국립공원 아고산대 독립훼손지 복원식생 분포특성 및 관리방안

김종엽(Jong-Yup Kim),윤주웅(Ju-Ung Yun),한봉호(Bong-Ho Han),곽정인(Jeong-In Kwak),박석철(Seok-Cheol Park),박수영(Su Young Park),정원옥(Won-Ok Jeong) 국립공원연구원 2022 국립공원연구지 Vol.13 No.1

본 연구는 독립훼손지 중 아고산대에 위치한 지리산국립공원 세석평전과 노고단 복원식생지를 대상으로 현존식생 분석 및 식생분포 특성을 파악하여 중장기적인 모니터링 및 관리방안 수립을 위한 기초자료를 제공하고자 수행하였다. 현존식생 조사범위는 훼손지 일대 유역권분포 현황을 고려하여 설정하였으며, 세석평전 조사면적은 55,037㎡, 노고단 조사면적은 166,599㎡ 이었다. 세석평전은 초본층에 의한 식생피복도는 90% 이상 수준으로서 나지노출이 없었고, 관목층의 피복도가 60% 이상으로 안정화되어 있었다. 주요 출현수종은 구상나무, 사스래나무, 쇠물푸레나무, 철쭉, 털진달래, 붉은병꽃나무 등 식재수종과 자연적으로 이입한 자생수종이 생육하고 있었다. 노고단은 신갈나무, 호랑버들, 철쭉, 털진달래, 미역줄나무 등이 우점하는 관목식생지가 52%로 가장 넓게 분포하고 있었고, 전반적으로 식생활착 상태가 양호하였다. 노고단의 원식생은 신갈나무군락으로 추정되었고, 군부대철거지에는 귀화식물이 분포하고 있기 때문에 적극적인 관리가 필요하였다. 연구대상지는 장기적으로 주변 자연식생과 조화로운 식생경관으로 발달할 것으로 예측되었다. 향후 훼손지 복원모델은 인근 지역의 원식생을 고려하여 설정해야 할 것이지만, 복원 달성 목표는 실현가능한 수준의 목표를 설정해야 할 것이다. This study was conducted to provide basic data for mid-to long-term monitoring and establishment of management plans by analyzing the existing vegetation and identifying the vegetation distribution characteristics for the restored vegetation in Nogodan and Seseokpyeongjeon in Jirisan National Park located in the subalpine zone among the independent damaged areas. Actual vegetation survey range was established in consideration of the distribution of the watershed around the damaged area. The surveyed area of Seseokpyeongjeon was 55,037㎡, and the surveyed area of Nogodan was 166,599㎡. In Seseokpyeongjeon, the vegetation coverage by the herbaceous layer was almost 90% or more, there was no bare exposure, and the coverage of the shrub layer was stabilized at 60% or more. The main emerging tree species were planted species such as Abies koreana, Betula ermanii, Fraxinus sieboldiana, Rhododendron schlippenbachii, Rhododendron mucronulatum var. ciliatum, and Weigela florida as well as natively migrated native species. In Nogodan, the shrub vegetation dominated by Quercus mongolica, Salix caprea, Rhododendron schlippenbachii, Rhododendron mucronulatum var. ciliatum, and Tripterygium regelii was the most widely distributed with 52% of the area, and the overall diet was good. The native vegetation of Nogodan was presumed to be a cypress colony. Naturalized plants were distributed in the military base demolition site, so active management was required. The study site was predicted to develop into a vegetation landscape in harmony with the surrounding natural vegetation in the long term. In the future, the restoration model for damaged areas should be set in consideration of the native vegetation of the nearby area, but the goal to achieve restoration should be set at a feasible level.

지역난방배관의 다중누수 감지기 개발에 관한 연구

한상만,박한석,변기식 釜慶大學校 1998 釜慶大學校 論文集 Vol.3 No.2

Local heating transportation pipe has sensor and return lines to detect water- leakage. There are impulse and resistance comparison measurementtypes for a water-leakage detection. The impulse type shows large detection error within a measurement range. Since the resistance comparison type can find a comparative accurate single water-leakage point in the measurement range of heating pipe. it has used to detect water-leakages these days. However if the multi water-leakages are happened in the measurement range of trange of transportation pipe. the resistance comparison type shows a detection error point by the parallel resistance between a detection sensor line and ground. But the detection error will be minimized by the divided transportation pipe loops. In this research, it suggests the design of remote controlled detector which can divide a large pipe loop and a possible single water-leakage measurement process in each divided loops.

횡문근 융해증의 Tc-99m Methylene Diphosphonate 신티그라피 소견

한창진,박찬희,윤석남,배문선,김수지,신규설 아주대학교 1997 아주의학 Vol.2 No.2

Many causes of rhabdomyolysis have been reported in the literature. Technetium-99m methylene dipho-sphonate (Tc-99m MDP) bone scintigraphy is considered to be the most sensitive and effective modality in defining the extents of disease involvement and follow-up of patients with rhabdomyolysis. In this paper, we reviewed two cases of generalized rhabdomyolysis related to seizure activities and two cases of localized rhabdomyolysis related to an excessive exercise. In addition other causes of rhabdomyolysis and possible mechanisrns of Tc-99m MDP uptake are discussed briefly.

초음파법을 이용한 콘크리트 역타시공 이음부 공극의 화상검출특성

박석균,백운찬,이한범,김명모 한국비파괴검사학회 2000 한국비파괴검사학회지 Vol.20 No.4

최근 역타시공법 등에 의한 콘크리트 구조물의 시공이 증가 추세에 있다. 이 경우, 자주 발생되는 신ㆍ구타설 콘크리트 시공이음부의 공극은 향후 구조물의 구조적인 특성과 내구성 등에 큰 영향을 미치게 된다. 그러나 현재 제안되고 있는 비파괴 검사법으로는 효과적으로 이음부 공극을 평가하기에 많은 한계가 있다. 본 연구에서는 시공이음부의 콘크리트 충전상태를 평가하기 위해 철골철근 콘크리트와 무근 콘크리트 시험체내에 공극을 모의제작한 후, 초음파속도 측정을 실시하고, 화상처리기법을 이용하여 비교적 용이하게 해석 가능한 방법에 대해 검토하였다.

Nortriptyline 청소율과 Metoprolol 산화대사능과의 상관관계

정원석,장인진,이경훈,신상구,우종인,박찬웅 大韓臨床藥理學會 1993 臨床藥理學會誌 Vol.1 No.2

초음파법을 이용한 콘크리트 시공이음부 공극 및 내부공동의 화상검출 해석에 관한 연구

박석균,백운찬,이한범 대전대학교 산업기술연구소 2000 산업기술연구소 論文集 Vol.11 No.2

The joint and void treatment of concrete is one of the technical problems in construction. Joints and voids created with the construction result in serious weakness from the aspects of both structural and water-barrier function. Ultrasonic image processing technique was used for the inspection of construction joints of SRC(Steel-frame Reinforced Concrete) column and voids of concrete block in this study. The advantages and limitations of this technique for non-destructive inspection in construction joints and voids are investigated. As a result, it has been verified that the semi-direct measurement type is more effective than the other types for detecting the construction joints and voids using ultrasonic method.

인터넷 서비스 유형분석 모델 개발에 관한 연구

박주석,박진휘,이한규 한국경영과학회 2001 한국경영과학회 학술대회논문집 Vol.- No.1(2)

Electronic Commerce grows rapidly in the past few years. Also, the power of EC doesn't become weak in the future. The increase of EC market scale provides powerful foundation to the Internet development. Unlike other technology, Internet has several distinctive character. First, As Internet spreads fast to the public, it became the usable technology to them in a short time. Second, Comparing to other technology, the work with using Internet isn't difficult to public so the basis of technology prepared in a short period. Third, Internet applicates all the industry and economic so, it makes economic foundation for making synergy during a short period. These Internet characters influence to EC growing speed which is basement of Internet growth. Due to Digital revolution giving much more influence than last Industrial Revolution, E-Business such as e-Management, B2B, B2C became the survival strategies for enterprise's management efficiency. Owing to emergence of technology like ultrahigh speed data communication, Broadband communication, wireless Internet, Internet TV, IS95C(2.5GB), 3G and activation of internet business, products and service through Internet become realized. Because of this, Supply of products and service through Internet are on the increase. But demand of voice communication become saturated, so increase of profit and sale through it reach the limit. Communication demand for products and service is a growing tendency. Consequently, research about vision and business strategies of Internet service for promoting the business founded on internet required.

진화프로그래밍에 의한 반도체 웨이퍼 운반시스템의 스케쥴링 알고리즘

한석원,박태형 충북대학교 컴퓨터 정보통신 연구소 2000 컴퓨터정보통신연구 Vol.8 No.1

다수 대의 자성운반체에 의하여 웨이퍼의 공급 및 반송이 이루어지는 반도체 제조시스템의 생산성 향상을 위한 스케쥴링 방법을 제안한다. 진화프로그래밍의 사용을 위하여 염색체의 정의하며, 교배 및 돌연변이 함수를 새로이 정의한다. 또한 각 자성운반체의 충돌회피를 위한 시간 창 기법을 적용한다. 기존 방법과의 비교 시뮬레이션을 통하여 제시된 방법의 유용성을 검증하며, 실제 생산라인에의 적용방법을 제시한다. We propose a new path planning method for multiple magnetic carriers in wafer handling systems. The chromosome and the genetic operators are defined to solve the problem by genetic algorithms. The time-window technique is also applied to the method to generate a conflict-free path of each magnetic carrier. Simulation results are then presented to verify the usefulness of the proposed scheme.

계층분석법을 이용한 적정 수변구역 결정에 관한 연구

한혜진,박석순 한국물환경학회 2004 한국물환경학회지 Vol.20 No.6

This paper presents the development and application of a riparian buffer zone design model(RBZDM). The model was developed as a decision-making tool for watershed management, by integrating geographic information system(GIS) and analytical hierarchy process(AFIP) theory. Several factors for watershed management, such as pollution removal capacity, land aquisition cost, distribution of point and non-point pollution sources, and possibility of new pollution source location, were analyzed based on AHP theory. The vegetated buffer zone width was designed using GIS-based riparian buffer analysis. The developed model was applied to the Kyoungan Stream watershed, which is an important part of Paldang lake catchment area. The Kyoungan stream watershed was divided into sixteen subbasins. Six of them belong to the main stem, where the model was applied. Ten alternatives of buffer zone width and five hierarchial levels were designed. The relative importance and the relative preference were computed by pair-wise comparison of evaluation criteria given in hierarchial levels. The buffer zone width was determined by linear function of the given alternatives and relative preferences. From this study, it was determined that the six buffer zone widths of Kyoungan main stems would be 1,594, 1,744, 1,856, 1,782, 1,338, 1,780 meter, from upstream to downstream.