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.

An Investigation of the Stability of Y₂O₃ and Sintering Behavior of Fe-Based ODS Particles Prepared by High Energy Ball Milling

Park, Eun-Kwang,Hong, Sung-Mo,Park, Jin-Ju,Lee, Min-Ku,Rhee, Chang-Kyu,Seol, Kyeong-Won The Korean Powder Metallurgy Institute 2013 한국분말재료학회지 (KPMI) Vol.20 No.4

Fe-based oxide dispersion strengthened (ODS) powders were produced by high energy ball milling, followed by spark plasma sintering (SPS) for consolidation. The mixed powders of 84Fe-14Cr-$2Y_2O_3$ (wt%) were mechanically milled for 10 and 90 mins, and then consolidated at different temperatures ($900{\sim}1100^{\circ}C$). Mechanically-Alloyed (MAed) particles were examined by means of cross-sectional images using scanning electron microscopy (SEM). Both mechanical alloying and sintering behavior was investigated by X-ray diffraction (XRD) and high resolution transmission electron microscopy (HR-TEM). To confirm the thermal behavior of $Y_2O_3$, a replica method was applied after the SPS process. From the SEM observation, MAed powders milled for 10 min showed a lamella structure consisting of rich regions of Fe and Cr, while both regions were fully alloyed after 90 min. The results of sintering behavior clearly indicate that as the SPS temperature increased, micro-sized defects decreased and the density of consolidated ODS alloys increased. TEM images revealed that precipitates smaller than 50 nm consisted of $YCrO_3$.

The Korean Association of lnternal Medicine : Poster Session ; PS 1357 : Nephrology ; Age is the Strongest Effector for the Relationship between Estimated Glomerular filtration Rate and Coronary Artery Calcifi cation in Apparently Healthy Korean Adults

( Hyun Beom Chae ),( Eun Jung Rhee ),( Hae Jung Park ),( Min Kyung Lee ),( Won Seon Jeon ),( Se Eun Park ),( Cheol Young Park ),( Won Young Lee ),( Ki Won Oh ),( Sung Woo Park ) 대한내과학회 2014 대한내과학회 추계학술발표논문집 Vol.2014 No.1

Background: Cardiovascular disease (CVD) is a major clinical problem and the most common cause of morbidity and mortality in patients with chronic kidney disease (CKD). Coronary artery calcifi cation (CAC) is a potential mechanism that explains the association between renal function and cardiovascular mortality. We aimed to evaluate the association between renal function and CAC in apparently healthy Korean subjects. Methods: In 23,617 participants in the health screening program in Kangbuk Samsung Hospital health screening program from January 2010 to December 2011, estimated glomerular fi ltration rate (eGFR) was assessed by Cockcroft-Gault equation. Coronary artery calcium score (CACS) was measured by multi-detector computed tomography (MDCT). Subjects were divided into 3 groups according to the CKD Staging system with eGFR grade; stage 1: eGFR = 90 mL/min/1.73 m2, stage 2: eGFR 60-89 mL/ min/1.73 m2, stage 3: eGFR 30-59 mL/min/1.73 m2. Results: Mean age of the participants was 41.4 years, and mean eGFR was 103.6±21.7 mL/min/1.73 m2. Hypertension and diabetes were noted in 43.7% and 5.5% of the participants, respectively. eGFR showed weakly negative but signifi cant association with CACS in bivariate correlation analysis (r=-0.076, p<0.01). Mean CACS signifi cantly increased from CKD stage 1 to 3. The proportion of subjects who had CAC signifi cantly increased from CKD stage 1 to 3. Although odds ratio for CAC signifi cantly increased from stage 1 to 3 after adjustment for confounding factors, this signifi cance was inversed when age was included in the model. Age was the strongest factor that affects CAC. Conclusions: This study performed in young Korean subjects with relatively normal renal function, age was the mostly strongest effector on the association between eGFR and the degree of CAC.

NURB 곡선을 이용한 GIS 도체표면의 전계최적화

민석원,박은서 순천향대학교 부설 산업기술연구소 2001 순천향 산업기술연구소논문집 Vol.7 No.2

This paper aims at the design of 170 kV GIS conductor surface under a certain specified field condition by using NURB curves. We used 170 kV GIS model as initial shape and selected the reference electric field on the GIS conductor surface as 1.2 kV/min which was middle between average value and maximum value on it. We found the maximum electric field on conductor surface was 1.25kV/min and other parts was converged in 1.2 kV/min when we optimized the total part of 170 kV GIS conductor surface by using two shape variables.

비만학생들의 운동후 회복시 초과 산소소비량 및 지속시간에 관한 연구

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 examine the effect of two different intensity of continuous exercise on magnitude of excess post-exercise oxygen consumption(EPOC), energy consumption following a 20min treadmill exercise. The subjects of this study were eight super-obesity in middle school students who were above 13 years old. subjects participated in two different exercise intensity to measure respiratory gas, blood lactate concentration and eardrum temperature. The results of this study were as follows: 1. The Energy consumption of the high intensity (80% VO₂ max) exercise group (264.68 35.60cal) was greater than that of the low intensity (50%) exercise group(172.01 20.39 Cal)(p<.001). 2. The EPOC of the high intensity exercise group (22.36+ 6.82Cal ) was greater than that of the low intensity exercise group(15.39+5.27 Cal)(p<.001). 3. The EPOC duration of th high intensity exercise group(28.36=3.56min) was longer than that of the low intensity exercise group(17.23+1.25min)(p<.001) 4. The blood lactate concentration, respiratory exchange ratio and temperature of the high intensity exercise group were greater than those of the low intensity exercise group(p<.05,p<.01). EPOC and duration were increase with 80%VO₂max, 80% VO₂max as intensity exercise got higher this also showed that it had something to do with lactate concentration in blood and increase of body temperature in the conclusion. We considered that there was a difference in using methods of energy, as there was a similar difference in RER. We though this following with oxygen consumption after exercise, we could clarify that high intensity exercise was better than lower intensity exercise in sametime for those who are obese especially adolescents to maintain their weights on the aspect of effect.

Clothing Pressure of selected Support Panty Stockings

(Jeong Eun Park),(Su Kwang Sung),(Min Kyu Song) 한국의류산업학회 2000 한국의류산업학회지 Vol.2 No.5

The purpose of the study was to obtain the basic data on the self-adjusting ability of the support panty stockings. Ten healthy women in the twenties were selected as subjects and clothing pressure of 9 support panty stockings made of single covered yarn (SCY) and double covered yarn (DCY) were measured under the standard environmental condition for the study. Data was analysed statistically according to body postures, sides, and parks. The results were as follows: Clothing pressure according to body posture was order of `sitting-on-a-chair`, `stepping-up-a-stair`, and `standing`. High clothing pressure was obtained in the parts of calf (9.4 gf/㎠) in `standing` and knee (9.7 and 16.5 gf/㎠) in both `stepping-up-a-stair` and `sitting-on-a-chair`, respectively. The order of clothing pressure with body sides was `front`, `side`, and `back`. The highest clothing pressure was knee (18.8 gf/㎠) on the front, thigh (8.8 gf/㎠) on the side, and calf (6.4 gf/㎠) on the back. Clothing pressure of DCY at abdomen and knee was a little higher than those of SCY 3. In terms of material structure variation, clothing pressure of thigh, calf and ankle with SCY was a little higher than those with DCY, while clothing pressure of abdomen and knee with DCY was a little higher than those with SCY.

오이 추출물에 존재하는 Superoxide Dismutase의 열안정성

김은애(Eun-Ae Kim),김기남(Gi-Nahm Kim),길지은(Ji-Eun Kil),이민경(Min-Kyung Lee),김석환(Suk-Hwan Kim),서정식(Chung-Sik Suh),박인식(Inshik Park) 한국식품영양과학회 1999 한국식품영양과학회지 Vol.27 No.6

오이속의 조효소액에 존재하는 Superoxide dismutase(SOD)활성의 pH 안정성은 pH 8.0에서 가장 안정하였고 pH5.0~9.0 사이의 범위에서는 비교적 안정하였다. 최적 온도는 25℃였고 열 안정성은 60℃까지는 안정하였다. 100℃에서 5분간 보관하였을 경우에는 12%만이 남아있었다. 오이에 존재하는 SOD 활성이 섭취 후에도 안정한가를 확인하기 위한 실험에서는 위속의 pH와 동일하도록 오이속의 조효소액의 pH를 2.0으로 변형시킨 후 36.7℃에서 3시간 동안 보관 후에 잔존활성이 10%였고, 장내의 환경인 pH 7.0으로 바꾸어 6시간 동안 둔 후 잔존하는 SOD의 활성은 25%로 활성이 증가되었다. 다양한 열처리 후에 잔존하는 오이의 SOD활성은 오이속은 데치기에서(끓는 물에서 2분) 25%, 껍질은 찌는 동안에(3분) 53%, 그리고 속과 껍질로 분리하지 않은 오이는 데치기에서 27%의 활성잔존률을 보였다. 4℃에서는 20일간 보관한 후에 오이속의 조효소액은 81%활성이 있었고, 30℃에서는 17%의 활성이 남아 있었다. 투석한 결과 SOD의 활성은 변화가 없었으므로 오이속에 존재하는 SOD는 적어도 분자량이 12,000 이상의 물질로 추정된다. The superoxide dismutase(SOD) in peeled pericarp of cucumber was most stable at pH 8.0 and relatively stabe between pH 5.0 and 9.0. The enzyme was stable up to 60℃ and retained 12% by heat treatment at 100℃ for 5 min. At pH 2.0, the peeled pericarp enzyme activity was decreased to 10% by incubation for 3 hrs. However, the enzyme activity was increased above 25% after incubating the enzyme at pH 7.0 for 6 hrs. Retention of SOD activity in cucumber by various heating methods was also measured. The residual SOD activities of peeled pericarp and whole cucumber was estimated to be 25% and 27% after blanching (2 min), respectively. The skin enzyme retained 53% of its activity after steaming (3 min). When the peeled peri carp enzyme was incubated at 4℃ for 20 days, the enzyme activity remained about 81%. However, when the enzyme incubated at 30℃ for 20 days, the peeled pericarp enzyme activity decreased to 17% of its original activity. The enzyme activity of peeled pericarp cucumber was not changed after exhaustive dialysis for 3 days, which indicated that the SOD activity in cucumber seems to have molecular weight above 12,000.

금불초 꽃 추출물의 항균 및 항산화 활성

김은희 ( Eun Hee Kim ),김정은 ( Jung Eun Kim ),김규희 ( Kyu Hee Kim ),나의연 ( Eui Yeon Na ),이상기 ( Sang Ki Lee ),정현민 ( Hyun Min Jeong ),이현준 ( Hyun Jun Lee ),박수남 ( Soo Nam Park ) 대한화장품학회 2009 대한화장품학회지 Vol.35 No.3

본 연구에서는 금불초 꽃 추출물의 피부 상재균에 대한 항균작용과 항산화, tyroinase 저해 효과에 관한 조사를 수행하였다. 피부 상재균에 대한 항균활성 측정결과, P. acnes에 대한 ethyl acetate 분획의 MIC는 0.25 %로 나타났으며, methyl paraben과 비슷한 활성을 나타냈고 quercetin보다는 큰 항균활성을 나타내었다. 추출물의 free radical (1,1-diphenyl-2-picrylhydrazyl, DPPH) 소거활성(FSC₅₀)은 ethyl acetate 분획에서 8.55 μg/mL로 측정되었다. Luminol-의존성 화학발광법을 이용한 Fe³⁺-EDTA/H₂O₂계에서 생성된 활성산소종(reactive oxygen species, ROS)에 대한 금불초 꽃 추출물의 총 항산화능은 ethyl acetate 분획 0.24 μg/mL로, 50 % EtOH extract와 aglycone 분획 보다 ethyl acetate 분획에서 가장 큰 활성을 나타내었다. 금불초 꽃 추출물에 대하여 rose-bengal로 증감된 사람 적혈구의 광용혈에 대한 억제 효과를 측정하였다. 금불초 꽃 추출물의 경우 5 ~ 100 μg/mL의 농도에서 광용혈을 억제하였다. 특히 당을 제거시킨 플라보노이드 aglycone 분획은 25 μg/mL 농도에서 τ₅₀이 164.15 min으로 매우 큰 세포보호 효과를 나타내었다. 미백 효과측정으로는 각각 tyrosinase의 활성 저해 효과를 측정하였다. Tyrosinase의 활성 저해 효과 (IC₅₀)는 ethyl acetate 분획에서 87.03 μg/mL 로 나타났다. 이상의 결과들은 금불초 꽃 추출물이 ¹O₂ 혹은 다른 ROS를 소광시키거나 소거함으로써 그리고 ROS에 대항하여 세포막을 보호함으로써 생체계, 특히 태양 자외선에 노출된 피부에서 항산화제로서 작용할 수 있음을 가리키며, 금불초 꽃 성분 분석, ethyl acetate 분획의 tyrosinase 저해활성 그리고 피부 상재균에 대한 항균작용으로부터 항산화, 항노화 및 항균성 화장품 소재로서의 응용 가능성을 확인하였다. In this study, the antibacterial activity, antioxidative effects, inhibitory effects on tyrosinase of Inula britannica flower extracts were investigated. MIC values of ethyl acetate fraction from Inula britannica flower on P. acnes 0.25 %, respectively. The results showed that the antibacterial activity of the ethyl acetate fraction was the highest in the P. acnes. The free radical (1,1-diphenyl-2-picrylhydrazyl, DPPH) scavenging activities (FSC₅₀) of ethyl acetate fraction of Inula britannica flower was 8.55 μg/mL. Reactive oxygen species (ROS) scavenging activities (OSC₅₀) of some fInula britannica flower extracts on ROS generated in Fe³⁺- EDTA/H₂O₂ system were investigated using the luminol-dependent chemiluminescence assay. The order of ROS scavenging activities were ethyl acetate fraction 0.24 μg/mL. Ethyl acetate fraction showed the most prominent ROS scavenging activity. The protective effects of extract/fractions of Inula britannica flower on the rose-bengal sensitized photohemolysis of human erythrocytes were investigated. The Inula britannica flower extracts suppressed photohemolysis in a concentration dependent manner (5 ∼ 100 μg/mL), particularly deglycosylated flavonoid aglycone fraction exhibited the most prominent celluar protective effect (τ₅₀, 164.15 min at 25 μg/mL). The inhibitory effect of Inula britannica flower extracts on tyrosinase was investigated to assess their whitening efficacy. Inhibitory effects (IC₅₀) on tyrosinase of some Inula britannica flower extracts were high. Ethyl acetate fraction has IC₅₀ of 87.03 μg/mL. These results indicate that extract/ fractions of Inula britannica flower can function as antioxidants in biological systems, particularly skin exposed to UV radiation by scavenging ¹O₂ and other ROS, and protect cellular membranes against ROS. And inhibitory activity on tyrosinase of the ethyl acetate fraction and high potential as bactericide against the skin pathogenic bacteria could be applicable to new functional cosmetics for antioxidant, antiaging, antibacterial activity.

A study on the removal of sulfate and nitrate from the wet scrubber wastewater using electrocoagulation

Jo, Eun-young,Park, Seung-Min,Yeo, In-seol,Cha, Jae-doo,Lee, Ju Yeol,Kim, Young-Hee,Lee, Tae-Kwon,Park, Chan-gyu Informa UK (Taylor Francis) 2016 Desalination and Water Treatment Vol.57 No.17

<P>Wet scrubber is widely used to remove pollutants from a furnace flue gas or from other gas streams. However, high cost for the treatment or exchange of contaminated washed water is one of the problems. Electrocoagulation (EC) is an electrochemical method for treating polluted water, whereby sacrificial anodes dissolve to produce active coagulant precursors in the solution. This technology can be used for the removal of color, anionic contaminants, and colloidal particles. The goal of the present study was evaluation of EC process for treatment of wet scrubber wastewater and optimization of the process. In this study, the influence of electrode material and electrode distance on removal efficiency (%) of nitrate, sulfate, and total suspended solids (TSS) was investigated with synthetic wastewater. Using an Al electrode, 60.6% of nitrate, 50.0% of sulfate, and 96.8% of TSS were removed by EC treatment within 30 min. In case of Fe electrode, 69.7% of nitrate, 75.0% of sulfate, and 98.8% of TSS were removed. The treatment efficiency for real wet scrubber wastewater was evaluated with Fe electrode. After 180 min of EC treatment, 50% of color, 40% of nitrate, 40% of sulfate, and 95% of TSS were removed, respectively. All these results give clear evidence that EC process can effectively reduce the TSS, nitrate, and sulfate ions from wet scrubber wastewater.</P>

갑상선 기능항진증 환자에서 인슐린감수성 및 인슐린분비능의 변화

최은진,강호철,이태희,정민영,이대호,장연진,박상선,조재현 대한내분비학회 1994 Endocrinology and metabolism Vol.9 No.2

The impairement of glucose metabolism is frequently associated in hyperthyroidism. The present study was performed to determine the effect of the thyroid hormone excess on insulin sensitivity and on insulin secretory function in vivo. Ten newly diagnosed hyperthyroid patients and fifteen healthy control subjects were subjected to frequently sampled intravenous glucose tolerance tests(FSIGT) after an overnight fast. Insulin sensitivity, represented by the insulin sensitivity index(S_1), was assessed by minimal model analysis of FSIGT data. Insulin secretion was measured by the total area under the insulin curve after glucose load. The results were as follows. 1) The K_G values, which represent glucose tolerance, were not different between the hyperthyroid patients and the normals(2.2+-0.3 vs. 2.5+-0.3%/min, p$gt;0.05). 2) S_1 was significantly decreased in the hyperthyroid patients in comparison to the normals(7.5+-1.4 vs. 2.6+-0.3X10^-4 min^-1/uU/ml, p$lt;0.05). 3) The basal insulin concentration was higher in the hyperthyroid patients than in the normals(8.3+-2.4 vs. 4.6+-0.4 uU/ml, p=0.07). In addition, the insulin secretory response to a glucose load was increased in the hyperthyroid patients as evidenced by the peak plasma insulin level(168.2+-30.4 vs. 89.2+-13.9 uU/ml, p$lt;0.05) and by the total area under the insulin curve(2641.1+-443.2 vs. 1696.7+-204.3 min uU/ml, p$lt;0.05). These results clearly demonstrated that insulin sensitivity was impaired in these newly diagnosed hyperthyroid patients. However, glucose tolerance was maintained by the increased insulin secretion (J Kor Soc Endocrinol 9:108-114, 1994).