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Axonal Neuropathy-associated TRPV4 Regulates Neurotrophic Factor-derived Axonal Growth
Jang, Yongwoo,Jung, Jooyoung,Kim, Hyungsup,Oh, Jungeun,Jeon, Ji Hyun,Jung, Saewoon,Kim, Kyung-Tai,Cho, Hawon,Yang, Dong-Jin,Kim, Sung Min,Kim, In-Beom,Song, Mi-Ryoung,Oh, Uhtaek American Society for Biochemistry and Molecular Bi 2012 The Journal of biological chemistry Vol.287 No.8
Yongwoo Jang,Wook-Joo Lee,홍규상,심원식 고려인삼학회 2015 Journal of Ginseng Research Vol.39 No.3
Background: Korean Red Ginsengda steamed root of Panax ginseng Meyerdhas long been used as a traditional medicine in Asian countries. Its antipruritic effect was recently found, but no molecular mechanisms were revealed. Thus, the current study focused on determining the underlying molecular mechanism of Korean Red Ginseng extract (RGE) against histamine-induced itch at the peripheral sensory neuronal level. Methods: To examine the antipruritic effect of RGE, we performed in vivo scratching behavior test in mice, as well as in vitro calcium imaging and whole-cell patch clamp experiments to elucidate underlying molecular mechanisms. Results: The results of our in vivo study confirmed that RGE indeed has an antipruritic effect on histamine-induced scratching in mice. In addition, RGE showed a significant inhibitory effect on histamine-induced responses in primary cultures of mouse dorsal root ganglia, suggesting that RGE has a direct inhibitory effect on sensory neuronal level. Results of further experiments showed that RGE inhibits histamine-induced responses on cells expressing both histamine receptor subtype 1 and TRPV1 ion channel, indicating that RGE blocks the histamine receptor type 1/TRPV1 pathway in sensory neurons, which is responsible for histamine-dependent itch sensation. Conclusion: The current study found for the first time that RGE effectively blocks histamine-induced itch in peripheral sensory neurons. We believe that the current results will provide an insight on itch transmission and will be helpful in understanding how RGE exerts its antipruritic effects.
Jang, Yongwoo,Lee, Wook-Joo,Hong, Gyu-Sang,Shim, Won-Sik The Korean Society of Ginseng 2015 Journal of Ginseng Research Vol.39 No.3
Background: Korean Red Ginseng-a steamed root of Panax ginseng Meyer-has long been used as a traditional medicine in Asian countries. Its antipruritic effect was recently found, but no molecular mechanisms were revealed. Thus, the current study focused on determining the underlying molecular mechanism of Korean Red Ginseng extract (RGE) against histamine-induced itch at the peripheral sensory neuronal level. Methods: To examine the antipruritic effect of RGE, we performed in vivo scratching behavior test in mice, as well as in vitro calcium imaging and whole-cell patch clamp experiments to elucidate underlying molecular mechanisms. Results: The results of our in vivo study confirmed that RGE indeed has an antipruritic effect on histamine-induced scratching in mice. In addition, RGE showed a significant inhibitory effect on histamine-induced responses in primary cultures of mouse dorsal root ganglia, suggesting that RGE has a direct inhibitory effect on sensory neuronal level. Results of further experiments showed that RGE inhibits histamine-induced responses on cells expressing both histamine receptor subtype 1 and TRPV1 ion channel, indicating that RGE blocks the histamine receptor type 1/TRPV1 pathway in sensory neurons, which is responsible for histamine-dependent itch sensation. Conclusion: The current study found for the first time that RGE effectively blocks histamine-induced itch in peripheral sensory neurons. We believe that the current results will provide an insight on itch transmission and will be helpful in understanding how RGE exerts its antipruritic effects.
Jang, Yongwoo,Lee, Sung Hoon,Lee, Byeongjun,Jung, Seungmoon,Khalid, Arshi,Uchida, Kunitoshi,Tominaga, Makoto,Jeon, Daejong,Oh, Uhtaek Society for Neuroscience 2015 The Journal of neuroscience Vol.35 No.34
<P>Bipolar disorder (BD) is a psychiatric disease that causes mood swings between manic and depressed states. Although genetic linkage studies have shown an association between BD and TRPM2, a Ca<SUP>2+</SUP>-permeable cation channel, the nature of this association is unknown. Here, we show that D543E, a mutation of <I>Trpm2</I> that is frequently found in BD patients, induces loss of function. <I>Trpm2</I>-deficient mice exhibited BD-related behavior such as increased anxiety and decreased social responses, along with disrupted EEG functional connectivity. Moreover, the administration of amphetamine in wild-type mice evoked a notable increase in open-field activity that was reversed by the administration of lithium. However, the anti-manic action of lithium was not observed in the <I>Trpm2</I><SUP>−/−</SUP> mice. The brains of <I>Trpm2</I><SUP>−/−</SUP> mice showed a marked increase in phosphorylated glycogen synthase kinase-3 (GSK-3), a key element in BD-like behavior and a target of lithium. In contrast, activation of TRPM2 induced the dephosphorylation of GSK-3 via calcineurin, a Ca<SUP>2+</SUP>-dependent phosphatase. Importantly, the overexpression of the D543E mutant failed to induce the dephosphorylation of GSK-3. Therefore, we conclude that the genetic dysfunction of <I>Trpm2</I> causes uncontrolled phosphorylation of GSK-3, which may lead to the pathology of BD. Our findings explain the long-sought etiologic mechanism underlying the genetic link between <I>Trpm2</I> mutation and BD.</P><P><B>SIGNIFICANCE STATEMENT</B> Bipolar disorder (BD) is a mental disorder that causes changes in mood and the etiology is still unknown. TRPM2 is highly associated with BD; however, its involvement in the etiology of BD is still unknown. We show here that TRPM2 plays a central role in causing the pathology of BD. We found that D543E, a mutation of <I>Trpm2</I> frequently found in BD patients, induces the loss of function. <I>Trpm2</I>-deficient mice exhibited mood disturbances and impairments in social cognition. TRPM2 actively regulates the phosphorylation of GSK-3, which is a main target of lithium, a primary medicine for treating BD. Therefore, abnormal regulation of GSK-3 by hypoactive TRPM2 mutants accounts for the pathology of BD, providing the possible link between BD and TRPM2.</P>
Potent synthetic and endogenous ligands for the adopted orphan nuclear receptor Nurr1
Jang Yongwoo,Kim Woori,Leblanc Pierre,Kim Chun-Hyung,Kim Kwang-Soo 생화학분자생물학회 2021 Experimental and molecular medicine Vol.53 No.-
Until recently, Nurr1 (NR4A2) was known as an orphan nuclear receptor without a canonical ligand-binding domain, featuring instead a narrow and tight cavity for small molecular ligands to bind. In-depth characterization of its ligand-binding pocket revealed that it is highly dynamic, with its structural conformation changing more than twice on the microsecond-to-millisecond timescale. This observation suggests the possibility that certain ligands are able to squeeze into this narrow space, inducing a conformational change to create an accessible cavity. The cocrystallographic structure of Nurr1 bound to endogenous ligands such as prostaglandin E1/A1 and 5,6-dihydroxyindole contributed to clarifying the crucial roles of Nurr1 and opening new avenues for therapeutic interventions for neurodegenerative and/or inflammatory diseases related to Nurr1. This review introduces novel endogenous and synthetic Nurr1 agonists and discusses their potential effects in Nurr1-related diseases.
장일광(Ilkwang Jang),이용우(Yongwoo Lee),조재명(Jae Myung Cho),홍성부(Sungboo Hong),장용훈(Yong Hoon Jang) 한국소음진동공학회 2024 한국소음진동공학회 논문집 Vol.34 No.2
The rapidly expanding use of electro-optical tracking systems (EOTSs) in various industries has led to an emphasis on improving their precision and stability. This study investigated an approach to optimize the installation angle of the spring-damper anti-vibration system of an EOTS, particularly in military applications. The spring-damper system was numerically simulated using a finite element analysis model, considering the constraints of a confined installation space. The potential of this system to counteract low-frequency vibrations, which is a limitation of traditional rubber-based systems, was explored. The optimal installation angle was determined by ensuring a uniform distribution of natural frequencies on all three axes (x, y, z) of vibration. The results indicated an optimal installation angle of 56.95°, which provided a balanced damping performance across all axes. The study concluded that this angle resulted in the most effective performance of the EOTS spring-damper anti-vibration system. These findings will contribute to the enhancement of EOTS stability and precision, thus potentially improving military operations.
Jang Suk-Yong,Cha Yonghan,Kim Yongwoo,Kim Kap-Jung,Kim Hayong,Choy Wonsik 대한의학회 2023 Journal of Korean medical science Vol.38 No.18
Background: The purpose of this study was to investigate the change in the incidence rate, length of hospital stay (LOS), in-hospital mortality rate, and surgical method of hip fractures during the coronavirus disease 2019 (COVID-19) pandemic in South Korea where lockdown restrictions were not implemented. Methods: We calculated the expected values of the incidence of hip fractures, in-hospital mortality and LOS of hip fracture patients in 2020 (COVID period) based hip fracture database of the Korean National Health Insurance Review and Assessment (HIRA) during a 9-year period from 2011 to 2019 (pre-COVID period). A generalized estimating equation model with Poisson distribution and logarithmic link function was used to estimate adjusted annual percent change (PC) of incidence rate and 95% confidence intervals (CIs). Then, we compared the annual incidence, in-hospital mortality rate and LOS in 2020 with the expected values. Results: The overall incidence rate of hip fracture in 2020 was not significantly different from the expected value (PC, −5%; 95% CI, −13 to 4; P = 0.280). In women, the incidence rate of hip fracture in age groups over 70 years was smaller than the predicted value (P < 0.001). The in-hospital mortality rate was not significantly different from the expected value (PC, 5%; 95% CI, −8 to 19; P = 0.461). The mean LOS was larger than the expected value by 2% (PC, 2%; 95% CI, 1 to 3; P < 0.001). In intertrochanteric fracture, the proportion of internal fixation was smaller than the predicted value by 2% (PC, −2%; 95% CI, −3 to −1; P < 0.001), and that of hemiarthroplasty was larger than the predicted value by 8% (PC, 8%; 95% CI, 4 to 14; P < 0.001). Conclusions: In 2020, the incidence rate of hip fracture did not significantly decrease, and inhospital mortality rate did not significantly increase compared to the expected rates, which were projected based on the HIRA hip fracture data from 2011 to 2019. Only LOS increased slightly.