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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>
Jiyeon Cheon,Jongsun Kim,Hyerim Kwon,Jiho Park,Daesik Park 한국양서ㆍ파충류학회 2023 한국양서·파충류학회 학술대회 Vol.2023 No.07
Korean clawed salamander larvae (Onychodactylus koreanus) mainly inhabit mountain valleys, unlike other Hynobius salamanders. This study aimed to reveal if predation pressure affects the distribution of O. koreanus larvae in the valleys through olfactory antipredator behavior tests. In summer, the larvae move downstream that increasing the chance of encountering potential fish predators. So, we wanted to know if antipredator behavior is acquired while first experiencing the predators or innate. First, we investigated the response of O. koreanus larvae to chemical cues (100%, 50%, 25%, and 0%) of crayfishes (Cambaroides similis) and minnows (Rhynchocypris oxycephalus). Second, after learning twice by mixing the target species and potential predators' chemical cues, we tested if antipredator behavior is shifted. Onychondactylus koreanus showed significant antipredator response to minow odors by reducing moved time and distance, but not to crayfish odors. In the second test, the larvae showed significant antipredator behavior regardless of whether they had learned about the predator or not. Our results demonstrate that minnows are potential predator of O. koreanus larvae and potentially affect the restriction of distribution of the larvae in the valleys. In addition, the second result suggests that antipredator response of O. koreanus to minow odors is innate.
Park Jiyeon,Lee Min Woo,Ahn Soo Hyun,Han Seungchul,Min Ji Hye,Cha Dong Ik,Song Kyoung Doo,Kang Tae Wook,Rhim Hyunchul 대한영상의학회 2023 Korean Journal of Radiology Vol.24 No.8
Objective: To investigate the association among the electrode placement method, electrode type, and local tumor progression (LTP) following percutaneous radiofrequency ablation (RFA) for small hepatocellular carcinomas (HCCs) and to assess the risk factors for LTP. Materials and Methods: In this retrospective study, we enrolled 211 patients, including 150 males and 61 females, who had undergone ultrasound-guided RFA for a single HCC < 3 cm. Patients were divided into four combination groups of the electrode type and placement method: 1) tumor-puncturing with an internally cooled tip (ICT), 2) tumor-puncturing with an internally cooled wet tip (ICWT), 3) no-touch with ICT, and 4) no-touch with ICWT. Univariable and multivariable Cox proportional-hazards regression analyses were performed to evaluate the risk factors for LTP. The major RFA-related complications were assessed. Results: Overall, 83, 34, 80, and 14 patients were included in the ICT, ICWT, no-touch with ICT, and no-touch with ICWT groups, respectively. The cumulative LTP rates differed significantly among the four groups. Compared to tumor puncturing with ICT, tumor puncturing with ICWT was associated with a lower LTP risk (adjusted hazard ratio [aHR] = 0.11, 95% confidence interval [CI] = 0–0.88, P = 0.034). However, the cumulative LTP rate did not differ significantly between tumorpuncturing with ICT and no-touch RFA with ICT (aHR = 0.34, 95% CI = 0.03–1.62, P = 0.188) or ICWT (aHR = 0.28, 95% CI = 0–2.28, P = 0.294). An insufficient ablative margin was a risk factor for LTP (aHR = 6.13, 95% CI = 1.41–22.49, P = 0.019). The major complication rates were 1.2%, 0%, 2.5%, and 21.4% in the ICT, ICWT, no-touch with ICT, and no-touch with ICWT groups, respectively. Conclusion: ICWT was associated with a lower LTP rate compared to ICT when performing tumor-puncturing RFA. An insufficient ablation margin was a risk factor for LTP.
Park Jiyeon,Su Min-Ying,김영욱 대한마취통증의학회 2022 Korean Journal of Anesthesiology Vol.75 No.6
Background: Previous studies have demonstrated that morphological changes in the suprascapular notch are closely associated with suprascapular nerve entrapment syndrome (SNES). Thus, we hypothesized that the suprascapular notch cross-sectional area (SSNCSA) could be a good diagnostic parameter to assess SNES. Methods: We acquired suprascapular notch data from 10 patients with SNES and 10 healthy individuals who had undergone shoulder magnetic resonance imaging (S-MRI) and had no evidence of SNES. T2-weighted coronal magnetic resonance images were acquired from the shoulder. We analyzed the SSNCSA at the shoulder on S-MRI using our image-analysis program (INFINITT PACS). The SSNCSA was measured as the suprascapular notch, which was the most affected site in coronal S-MRI images. Results: The mean SSNCSA was 64.50 ± 8.93 mm2 in the control group and 44.94 ± 10.40 mm2 in the SNES group. Patients with SNES had significantly lower SSNCSA (P < 0.01) than those in the control group. Receiver operating curve analysis showed that the best cut-off of the SSNCSA was 57.49 mm2, with 80.0% sensitivity, 80.0% specificity, and an area under the curve of 0.92 (95% CI [0.79, 1.00]). Conclusions: The SSNCSA was found to have acceptable diagnostic properties for detecting SNES. We hope that these results will help diagnose SNES objectively.