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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.
Arctic Primary Aerosol Production Strongly Influenced by Riverine Organic Matter
Park, Jiyeon,Dall’Osto, Manuel,Park, Kihong,Kim, Jung-Hyun,Park, Jongkwan,Park, Ki-Tae,Hwang, Chung Yeon,Jang, Gwang Il,Gim, Yeontae,Kang, Sujin,Park, Sanghun,Jin, Yong Keun,Yum, Seong Soo,Simó American Chemical Society 2019 Environmental science & technology Vol.53 No.15
<P>The sources of primary and secondary aerosols in the Arctic are still poorly known. A number of surface seawater samples-with varying degrees of Arctic riverine and sea ice influences-were used in a sea spray generation chamber to test them for their potential to produce sea spray aerosols (SSA) and cloud condensation nuclei (CCN). Our interdisciplinary data showed that both sea salt and organic matter (OM) significantly influenced the SSA production. The number concentration of SSA in the coastal samples was negatively correlated with salinity and positively correlated with a number of OM tracers, including dissolved and chromophoric organic carbon (DOC, CDOM), marine microgels and chlorophyll <I>a</I> (Chl-<I>a</I>) but not for viral and bacterial abundances; indicating that OM of riverine origin enhances primary aerosol production. When all samples were considered, transparent exopolymer particles (TEP) were found to be the best indicator correlating positively with the ratio number concentration of SSA/salinity. CCN efficiency was not observed to differ between the SSA from the various samples, despite differences in organic characteristics. It is suggested that the large amount of freshwater from river runoff have a substantial impact on primary aerosols production mechanisms, possibly affecting the cloud radiative forcing.</P> [FIG OMISSION]</BR>
Park Jiyeon,Kim Dong-Moung,Lee Jin-Ok,Park Hyeon-Chun,Ryu Brian Y.,Kim Ju Han,Lee Sug Hyung,Chung Yeun-Jun 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-
Despite growing evidence of the relevance of alternative splicing (AS) to cancer development and progression, the biological implications of AS for tumor behaviors, including papillary thyroid cancer (PTC), remain elusive. With the aim of further understanding the molecular and histological subtypes of PTC, we in this study explored whether AS events might act as new molecular determinants. For this purpose, AS profiles were analyzed in RNA-sequencing data from The Cancer Genome Atlas (TCGA) and from a Korean patient dataset. A total of 23 distinct exon-skipping (ES) events that correlated significantly with PTC oncogenic activity and differentiation scores were identified. The two top-ranked ES events, NUMA1_17515 in exon 18 of NUMA1 and TUBB3_38175 in exon 6 of TUBB3, showed high correlations with oncogenic activities and discriminated histological and molecular subtypes of PTC. Furthermore, two novel intron-retention (IR) events for TUBB3 were uncovered. All ES and IR events for the TUBB3 gene were predicted to induce nonsense-mediated mRNA decay. The relative abundances of intron reads in the PTC dataset from TCGA showed IR levels to differ significantly among PTC subtypes, possibly reflecting their different tumor behaviors. This study provides a landscape of AS changes among PTC subtypes and identified two significant AS events, NUMA1_17515 and TUBB3_38175, as potential AS biomarkers for PTC subclassification and characterization. The AS events identified in this study may be involved in the development of phenotypic differences underlying the functional characteristics and histological differentiation of PTCs.
( Jiyeon Park ),( Hyung Rae Cho ),( Keum Nae Kang ),( Kun Woong Choi ),( Young Soon Choi ),( Hye-won Jeong ),( Jungmin Yi ),( Young Uk Kim ) 대한통증학회 2021 The Korean Journal of Pain Vol.34 No.2
Background: Iliotibial band friction syndrome (ITBFS) is a common disorder of the lateral knee. Previous research has reported that the iliotibial band (ITB) thickness (ITBT) is correlated with ITBFS, and ITBT has been considered to be a key morphologic parameter of ITBFS. However, the thickness is different from inflammatory hypertrophy. Thus, we made the ITB cross-sectional area (ITBCSA) a new morphological parameter to assess ITBFS. Methods: Forty-three patients with ITBFS group and from 43 normal group who underwent T1W magnetic resonance imaging were enrolled. The ITBCSA was measured as the cross-sectional area of the ITB that was most hypertrophied in the magnetic resonance axial images. The ITBT was measured as the thickest site of ITB. Results: The mean ITBCSA was 25.24 ± 6.59 mm<sup>2</sup> in the normal group and 38.75 ± 9.11 mm<sup>2</sup> in the ITBFS group. The mean ITBT was 1.94 ± 0.41 mm in the normal group and 2.62 ± 0.46 mm in the ITBFS group. Patients in ITBFS group had significantly higher ITBCSA (P < 0.001) and ITBT (P < 0.001) than the normal group. A receiver operator characteristic curve analysis demonstrated that the best cut-off value of the ITBT was 2.29 mm, with 76.7% sensitivity, 79.1% specificity, and area under the curve (AUC) 0.88. The optimal cut-off score of the ITBCSA was 30.66 mm2, with 79.1% sensitivity, 79.1% specificity, and AUC 0.87. Conclusions: ITBCSA is a new and sensitive morphological parameter for diagnosing ITBFS, and may even be more accurate than ITBT.
Park, Jiyeon,Jang, Myoseon,Yu, Zechen American Chemical Society 2017 Environmental science & technology Vol.51 No.17
<P>The impact of authentic mineral dust particles sourced from the Gobi Desert (GDD) on the kinetic uptake coefficient of SO<SUB>2</SUB> was studied under varying environments (humidity, O<SUB>3</SUB>, and NO<SUB><I>x</I></SUB>) using both an indoor chamber and an outdoor chamber. There was a significant increase in the kinetic uptake coefficient of SO<SUB>2</SUB> (γ<SUB>SO</SUB><SUB>4</SUB><SUP>2–</SUP><SUB>,light</SUB>) for GDD particles under UV light compared to the value (γ<SUB>SO</SUB><SUB>4</SUB><SUP>2–</SUP><SUB>,dark</SUB>) under dark conditions at various relative humidities (RH) ranging from 20% to 80%. In both the presence and the absence of O<SUB>3</SUB> and NO<SUB><I>x</I></SUB>, γ<SUB>SO</SUB><SUB>4</SUB><SUP>2–</SUP><SUB>,light</SUB> and γ<SUB>SO</SUB><SUB>4</SUB><SUP>2–</SUP><SUB>,dark</SUB> greatly increased with increasing RH. The resulting γ<SUB>SO</SUB><SUB>4</SUB><SUP>2–</SUP><SUB>,light</SUB> of GDD particles was also compared to that of Arizona Test Dust (ATD) particles. The γ<SUB>SO</SUB><SUB>4</SUB><SUP>2–</SUP><SUB>,light</SUB> values of GDD were 2 to 2.5 times greater than those of ATD for all RH levels. To understand the photocatalytic act of dust particles, both GDD and ATD were characterized for the metal element composition of fresh particles, the aerosol acidity of aged particles, and the hygroscopic properties of both fresh and aged particles. We conclude that the difference in the formation of sulfate between GDD and ATD particles is regulated mainly by the quantity of the semiconductive metals in dust particles and partially by hygroscopic properties.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/esthag/2017/esthag.2017.51.issue-17/acs.est.7b00588/production/images/medium/es-2017-00588h_0004.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/es7b00588'>ACS Electronic Supporting Info</A></P>
Isolation of Deletion Mutants by Reverse Genetics in Caenorhabditis elegans
Park, Byung-Jae,Lee, Jin ll,Lee, Jiyeon,Kim, Sunja,Choi, Kyu Yeong,Park, Chul-Seung,Ahn, Joohong The Korean Society for Integrative Biology 2001 Korean journal of biological sciences Vol.5 No.1
Obtaining mutant animals is important for studying the function of a particular gene. A chemical mutagenesis was first carried out to generate mutations in C. elegans. In this study, we used ultraviolet-activated 4,5',8-trimethylpsoralen to induce small deletion mutations. A library of mutagenized worms was prepared for recovery of candidate animals and stored at $15^{\circ}C$ during screening instead of being made into a frozen stock library. In order to isolate deletion mutations in target genes, a polymerase chain reaction (PCR)-based screening method was used. As a result, two independent mutants with deletions of approximately 1.0 kb and 1.3 kb were isolated. This modified and improved reverse genetic approach was proven to be effective and practical for isolating mutant animals to study gene function at the organismal level.