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.

승강대 운동이 비만고등학생의 혈청 지질 및 아포지단백 대사에 미치는 영향

박철호,고봉민,박은경,우상헌,안민호 동아대학교 스포츠과학연구소 2000 스포츠科學硏究論文集 Vol.18 No.-

The purpose of this study was to investigate the effect of 12 wks before and after step test of obsese student in D high school in Pusan city, exercise group(7) performed 12 wks step test and control group(7), before and after subjects performed the maximal exercise thest on treadmile's 12 wks step test. Through the comparision and analysis of change serum lipids and apolipoprotein metabolism, the results of this study were as follows. 1.In 12 wks before and after step test at the rest time, exercise group was found to have a increase In TC(12.7%), TG(9.76%), LDL-C(13.8%) and to have a significant increase in HDL-C(11.3%), FFA(96.8%). 2.At the rest, the control group was found to have a little increase in TG(9.2%) and HDL-C(6.7%), and to have a significant increase in TC(9.2%), LDL-C(8.9%) and FFA(7.5%). 3.In 12 wks before and after step test at the maximal exercise, the exercise group was found to have a significant increase in TC(5.6%), HDL-C(20.2%) and FFA(54.3). 4.At the maximal exercise, were found to have a significant increase in TC(9.7%) and LDL-C(9.9%) in the control group. 5.In 12 wks before and after step test at the maximal exercise, the exercise group was found to have a significant increase in Apo A-I(8.0%). 6.Statistically, At the maximal exercise, were found to have a significant increase in Apo B(7.8%).

장기간의 40분 달리기 운동이 비만학생의 혈청 지질 및 아포지단백 대사에 미치는 영향

박철호,권민호,고봉민,박은경,우상헌 東亞大學校附設스포츠科學硏究所 1999 스포츠科學硏究論文集 Vol.17 No.-

The purpose of this study was to investigate the effect of 12 wks before and after running exercise of obsese student in D high school in Pusan city, exercise group(7) performed 12 wks running exercise and control group(7),before and after subjects performed the maximal exercise thest on treadmile's 12 wks running exercise. Through the comparision and analysis of change serum lipids and apoliporotein metabolism, the results of this study were as follows. 1. In 12 wks before and agter running exercise at the rest time,exercise group was found to have a great decrease in TC(8%),TG(29%),LDL-C(7%) and to have a significant in crease in HDL-C(20%),FFA(74%). 2. At the rest, the control group was found to have a little decrease in TG, HDL-C,LDL-C and to have little changes in TC and FFA. 3. In 12wks before and after running exercise at the maximal exercise, the exercise group was found to have a significant decrease in TC(18%),TG(23) and to have a significant in crease in HDL-C(20%),LDL-(25%),FFA(23%) and TG and HDL-C were found to have a significant change. 4. At the maximal exerxcise , were found to have little change in the control group. 5. Apo A-I in the exercise group was found not to have the change signicantly. but to have anincrease 5% at the rest time, 6% at the maximal exercise. And the control group was almost found not to have change. 6. Statically, Apo B in the exercise group was found not to have a signficant change, but to have the increase 12%at the maximal exercise and the control group was found not to have a change.

유아교사관련 학위논문의 경향 분석

고선미,박은혜 이화여자대학교 교육과학연구소 2000 교육과학연구 Vol.31 No.3

본 연구는 유아교사관련 논문을 연구문제별로 그 내용과 변인을 분석함으로서 현재까지 이루어진 유아교사에 관한 연구 동향의 기초 자료를 제공하고 앞으로 유아교사 관련 논문의 바람직한 연구방향을 함께 제시하는 것을 목적으로 하였다. 1974년부터 1999년 2월까지 발표된 석·박사 학위논문 중 유아교사와 관련된 총 292개 논문의 연구문제 976개를 분석한 결과 다음과 같은 결과를 얻었다. 첫째, 교사교육에 영향을 주는 요인과 교사의 행동이 연결된 연구가 가장 많았으나 교사교육과정에 대한 연구는 미흡하며 교사교육과정에 영향을 주는 요인과 교사교육과정 및 교사의 행동이 모두 연결된 연구는 거의 이루어지지 않았다. 둘째, 유아교사에 관한 학위논문에서 사용된 연구 변인은 개인적 변인이 기관 변인보다는 조금 더 많이 사용되었다. 개인적 변인은 인구통계학적인 외적 요인에 편중되어 있으며, 기고나 변인은 설립유형 및 기관유형 등에 편중되어 있었다. The purpose of this study was to analyze the trends in master´s thesis and doctoral dissertations in the area of early childhood teacher education.292 master´s thesis and doctoral dissertations published between 1972 and 1999 were analyzed according to Yarger and Smith(1990)´s category.Data were processed with a frequency and percentage were calculated.The results are as follows.First, most of the research were conducted to investigate the area of antecedent conditions, outcomes, or antecedent conditions,-outcomes relationships.But, much fewere research were done on the area of process.Special trends in the research questions in terms of period were not found.The second, personal research variables are more used than institutional research variables.Among the personal research variables, career, academic career, age, marriage status were the most frequently used.Among the institutional variables, kinds of establishments (public/private), the kinds of institution (kindergarten/ nursery/ day care center elementary school), the number of children, the number of class were most frequently used.

실험적 간경화 동물모델 비교

박은전,김재백,손동환,고건일 圓光大學校 藥品硏究所 1996 藥品硏究所報 Vol.11 No.1

Hepatic cirrhosis is a common response to chronic liver injury from many causes and is one of the most common cause of all deaths. This study was carried out to develop a suitable experimental hepatic cirrhosis in rats to understand this disease and to apply for the pharmacokinetic in disease state. Following three kinds of experimental models were induced; 1)Bile duct ligation/scission (BDL/S), 2) N,N-dimethylnitrosamine(DMN), 3)Carbon tetrachloride. The hepatic cirrhosis was characterized by examining the liver/body weight ratio, serum biochemical values, hydroxyproline content in liver and histological appearance in cirrhotic rat liver(hematoxylin & eosin). The results are as follows : (1) In BDL/S, the liver was enlarged to 250% of normal liver. In contrast the liver was shrinked to 48% and 78% of the normal liver in DMN and CCI₄, respectively. (2) In CCI₄ and BDL/S, the serum ALT, AST, ALP and total bilirubin levels were significantly increased to 200-300% of normal level, while ALT and total bilirubin level were significantly increased in DMN group. (3) Hydroxyproline content in cirrhotic rat liver was significantly 200-500% higher than that of normal liver. (4) Nodular formation with fibrosis was observed in BDL/S, DMN, CCI₄ induced cirrhotic rat liver.

靑少年의 異性交際왕 性에 대한 態度에 관한 硏究

고정자,박은령 동아대학교 생활과학연구소 2001 생활과학연구 논문집 Vol.9 No.-

The aims of this study are that teenagers learn the salutary intersexual friendship and sexual behavior for their mature personality growing up smooth by analysing the teenagers' intersexual relationship and sexual behavior. To achieve the purpose the themes of study are : First, general tendencies of the teenagers' intersexual friendship and the differencies of the teenagers' intersexual friendship according to the independent variables. Second, general tendencies of the teenagers' sexual behavior and the differencies of the teenagers' sexual behavior according to the independent variables. Third, the concern with teenagers' Intersexual friendship experience and sexual behavior. For this purpose, this study was surveyed 800 teenagers of senior high school located in Pusan. They were first and third year in their school of all questionnaires, 769 copies were used for the analysis of final data. Frequency, percentage, mean, standard deviation, chi-square test, t-test, ANOVA, correlate by SPSS compute program were performed for data treatment. The results of this study are as follows. 1.The general tendencies of the teenagers' intersexual friendship and the differencies of the teenagers' intersexual friendship according to the independent variables. Most teenagers think the teenagers' intersexual friendship is necessary but their intersexual friendship experiences are lower than their cognition of intersexual friendship necessity. Parents tend to aid their children's intersexual friendship and teenagers think intersexual friendship experiences are affirmative. Most questionnaires reply the reason that they do net associate with other sex is that they don't have chances. In gender, school, brothers and sisters, drinking, smoking factors, significant differencies were shown. 2.The general tendencies of the teenagers' sexual behavior and the differencies of the teenagers' intersexual friendship according to the independent variables. Teenagers regard that virginity is important. The interest of sex is very high and they feel sex is human's natural instinct. In gender, school, brothers and sisters, drinking, smoking factors, significant differencies were shown. 3.The concern with teenagers' Intersexual friendship experience and sexual behavior. As teenagers have experienced in Intersexual friendship, their sense of virginity is rare but their interests of sex is strong and view of sex is natural.

외음부와 자궁에 생긴 평활근종 1예

박혜인,이해혁,김태희,김정식,남계현,이권해,고은석 순천향의학연구소 2004 Journal of Soonchunhyang Medical Science Vol.10 No.2

The leiomyomas of the vulva are rare benign tumors the incidence is 0.024%~0.55% in women. There are no relationship between leiomyomas of the vulva and uterus. But there are some reports that leiomyomas of the vulva and uterus simultaneously. The leiomyomas of the vulva present without symptoms and excision with biopsy is treatment of choice. Tumors of the gynecological apparatus may present without symptoms, or they may mimic other common gynecological conditions. Because of this, any vulva mass must be considered cautiously. We reported this case with a brief review of the concerned literatures.

헤파셀정의 cross-over test에 의한 국내시판 제제와의 생물학적 동등성 시험

박은전,이성희,이미현,김혜주,손동환,고건일,김재백 圓光大學校 藥品硏究所 1995 藥品硏究所報 Vol.10 No.1

Interleukin-2와 결핵균 30 kDa 항원이 구개편도 및 말초혈액 T 세포 증식에 미치는 상승효과

박정규,박찬권,조은경,김화중,백태현,고필준,김병국,남부현,나기상,박찬일 충남대학교 의과대학 지역사회의학연구소 1995 충남의대잡지 Vol.22 No.1

Widespread use of BCG has not controlled tuberculosis, and more effective vaccines are clearly needed. Although chemotherapy will remain the mainstay of antituberculosis treatment, the use of adjunctive immunotherapeutic modalitites is attractive, particularly in persons with drug-resistant tuberculosis. Administration of IL-2 or IFN-γto tuberculosis patients enhance bacillary elimination. Cell-mediated immunity is the critical protective immune response in tuberculosis. Mycobacterial antigens are recognized by T cells and that elicit production of protective cytokines are potentially important vaccine antigens. The 30 kDa antigen is secreted in large quantities by growing mycobacteria. That antigen elicits greater proliferation in lymphocytes from healthy tuberculin reactors than healthy tuberculin nonreactors. In this study, the T lymphocyte proliferative responses to 30 kDa antigen from Mycobactrium tuberculosis H37Rv were examined by using tonsilar and peripheral blood lymphocytes from PPD(+) and PPD(-) tonsilectomized persons. When cultured with 30 kD antigen, tonsilar mononuclear leukocytes and T cells of PPD(+) demonstrated more ^3H-thymidine incorporation than PPD(-) persons (stimulation index was 2.5 and 1.9, 0.8 and 1.0, repectively). Peripheral blood mononuclear cells (PBMC) and peripheral blood T lymphocytes were shown the similar responses to this antigen. The combination of IL-2 and 30 kDa antigen elicited a significant proliferative responsiveness in tonsilar mononuclear leukocytes and T cells of PPD(+) persons (SI was 20 and 14.1). PBMC and peripheral blood T cells of PPD(+) persons were also shown a significant responsiveness, but PPD(-) persons did not show. These results demonstrate that the 30 kDa antigen and IL-2 have a synergistic stimulatory property in mycobacteria sensitizing lymphocytes.

환자 만족도 조사를 통한 QI활동의 효과 평가 : 일개 병원을 중심으로

박연옥,김미숙,고은정,김연정,홍창호 한국의료QA학회 1998 한국의료질향상학회지 Vol.5 No.2

Background : Evaluation of patient's satisfaction is one of the most important aspects of quality improvement. If the patient highly satisfies with the medical service provided in the hospital, he/she will be likely to visit the same hospital again. Patient's satisfaction of a particular hospital is directly correlated with hospital profits as well as reputation in the community. For this reason, various kinds of survey measuring satisfaction level have been performed and many kind of QI activities for enhancing the profits as well as reputation in the community. For this reason, various kinds of survey measuring satisfaction level have been performed and many kind of QI activities for enhancing the patient's satisfaction. This study is to find the effect of hospital QI activities on the patient's satisfaction level. Methods : After questionnares were developed, survey of measuring satisfaction level was performed in August. 1998. On the basis of survey results. Ql activities were carried out to attain the target point of 4.0 and subsequent survey was done in November. 1998. Results : With three main principles of "problem solving approach with kindness". "helping patient to participate in medical procedure with sufficient information", and "putting employees into practice of attitude with human respect", the average level of satisfaction was enhanced from 3.45 to 3.55 level. Also kindness level of employees was increased from 3.71 to 3.82. Level of dissatisfaction about insufficient explanation and unkind attitude was dropped from 69% to 48% and from 82% to 46% respectively. Conclusion : With the result of this study overall satisfaction level was enhanced. In order to keep these advantages a operation of Quality Improvement Task Force Team in each subject will be required.