황금작약탕이 DSS로 유발된 궤양성 대장염 생쥐 모델에 미치는 영향 : 장내 대사물질 변화를 포함하여

윤차경,강상미,손선아,유양희,김은주,손홍석,설재욱,나창수 대한한의학방제학회 2023 大韓韓醫學方劑學會誌 Vol.31 No.4

Background : To investigate the effect of Hwanggeumjackyak-tang (HJT) on Dextran sulfate sodium (DSS) induced ulcerative colitis. Methods : The experimental animals were divided into three groups; group 1, normal group(Normal); group 2, DSS-induced colitis and untreated group(UT+DSS); group 3, DSS-induced colitis and HJT 200 mg-treated group(HJT200+DSS). We evaluated cytotoxicity after HJT administration and confirmed the anti-inflammatory effect by histological changes in the intestine and genetic analysis of mucosal cells after HJT administration for each group. In addition, microbiological weapons and metabolites in faeces were examined, and the correlation between gut microbiome and metabolites was also investigated. Result : HJT was not observed to be cytotoxic, even at relatively high concentrations, and was effective in protecting the barrier and preventing intestinal inflammation by suppressing the increase in mucus secretion and the expression of inflammatory factors in mucosal cells. HJT treatment affected the increase in the amount and diversity of the gut microbiome in faeces and the increase in metabolites thought to be involved in alleviating inflammation in the gut. Conclusion : This study demonstrates the therapeutic potential of HJT in ulcerative colitis. Further studies should be carried out to confirm our findings. Acknowledgement : This research was supported by a Korea Innovation Foundation (INNIPOLIS) grant funded by the Korean government (Ministry of Science and ICT) through a science and technology project that opens the future of the region (grant number: 2021-DD-UP-0380).

Inhibition of ERK1/2 by silymarin in mouse mesangial cells

윤차경,조성일,이민영,전영진,이석기 대한약리학회 2017 The Korean Journal of Physiology & Pharmacology Vol.21 No.1

The present study aimed to show that pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-1β] synergistically induce the production of nitric oxide (NO) production in mouse mesangial cells, which play an important role in inflammatory glomerular injury. We also found that co-treatment with cytokines at low doses (TNF-α; 5 ng/ml, IFN-γ; 5 ng/ml, and IL-1β; 1.25 U/ml) synergistically induced NO production, whereas treatment with each cytokine alone did not increase NO production at doses up to 100 ng/ml or 50 U/ml. Silymarin, a polyphenolic flavonoid isolated from milk thistle (Silybum marianum), attenuates cytokine mixture (TNF-α, IFN-γ, and IL-1β)-induced NO production. Western blot and RT-PCR analyses showed that silymarin inhibits inducible nitric oxide synthase (iNOS) expression in a dose-dependent manner. Silymarin also inhibited extracellular signal-regulated protein kinase-1 and -2 (ERK1/2) phosphorylation. Collectively, we have demonstrated that silymarin inhibits NO production in mouse mesangial cells, and may act as a useful anti-inflammatory agent.

Radicicol Inhibits iNOS Expression in Cytokine-Stimulated Pancreatic Beta Cells

윤차경,박선주,리미홍,이민영,이군영,차만진,김옥현,유호진,윤상필,전영진,장인엽 대한약리학회 2013 The Korean Journal of Physiology & Pharmacology Vol.17 No.4

Here, we show that radicicol, a fungal antibiotic, resulted in marked inhibition of inducible nitric oxide synthase (iNOS) transcription by the pancreatic beta cell line MIN6N8a in response to cytokine mixture (CM: TNF-α, IFN-γ, and IL-1β ). Treatment of MIN6N8a cells with radicicol inhibited CM-stimulated activation of NF-κB/Rel, which plays a critical role in iNOS transcription, in a dose-related manner. Nitrite production in the presence of PD98059, a specific inhibitor of the extracellular signal-regulated protein kinase-1 and 2 (ERK1/2) pathway, was dramatically diminished,suggesting that the ERK1/2 pathway is involved in CM-induced iNOS expression. In contrast,SB203580, a specific inhibitor of p38, had no effect on nitrite generation. Collectively, this series of experiments indicates that radicicol inhibits iNOS gene expression by blocking ERK1/2 signaling. Due to the critical role that NO release plays in mediating destruction of pancreatic beta cells, the inhibitory effects of radicicol on iNOS expression suggest that radicicol may represent a useful anti-diabetic activity.

Therapeutic Inhibitors against Mutated BRAF and MEK for the Treatment of Metastatic Melanoma

류순효,윤차경,문애란,Amanda Howland,Cheryl A. Armstrong,Peter I Song 전남대학교 의과학연구소 2017 전남의대학술지 Vol.53 No.3

Melanoma is one of the most aggressive cancers in the world and is responsible for the majority of skin cancer deaths. Recent advances in the field of immunotherapy using active, adoptive, and antigen-specific therapeutic approaches, have generated the expectation that these technologies have the potential to improve the treatment of advanced malignancies, including melanoma. Treatment options for metastatic melanoma patients have been dramatically improved by the FDA approval of new therapeutic agents including vemurafenib, dabrafenib, and sorafenib. These kinase inhibitors have the potential to work in tandem with MEK, PI3K/AKT, and mTOR to inhibit the activity of melanoma inducing BRAF mutations. This review summarizes the effects of the new therapeutic agents against melanoma and the underlying biology of these BRAF inhibitors.

Therapeutic Effects of Synthetic Antimicrobial Peptides, TRAIL and NRP1 Blocking Peptides in Psoriatic Keratinocytes

류순효,Lindsey Broussard,윤차경,Brendon Song,David Norris,Cheryl A. Armstrong,Beom Joon Kim,Peter I Song 전남대학교 의과학연구소 2019 전남의대학술지 Vol.55 No.2

Psoriasis is a chronic, recurrent, heterogeneous, cutaneous inflammatory skin disease for which there is no cure. It affects approximately 7.5 million people in the United States. Currently, several biologic agents that target different molecules implicated in the pathogenic processes of psoriasis are being assessed in diverse clinical studies. However, relapse usually occurs within weeks or months, meaning there is currently no cure for psoriasis. Therefore, recent studies have discovered diverse new potential treatments for psoriasis: inhibitors of bacteria such as Staphylococcus aureus, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and neuropilin 1 (NRP1). A promising approach that has recently been described involves modifying antimicrobial peptides to develop new cutaneous anti-bacterial agents that target inflammatory skin disease induced by Staphylococcus. Increased expression of TRAIL and its death receptors DR4 and DR5 has been implicated in the pathogenesis of plaque psoriasis. In addition, TRAIL has the ability to inhibit angiogenesis by inducing endothelial cell death and by negative regulation of VEGF-induced angiogenesis via caspase-8-mediated enzymatic and non-enzymatic functions. Since NRP1 regulates angiogenesis induced by multiple signals, including VEGF, ECM and semaphorins, and also initiates proliferation of keratinocytes through NF-kB signaling pathway in involved psoriatic skin, targeting NRP1 pathways may offer numerous windows for intervention in psoriasis. In this review, we will focus on the current knowledge about the emerging role of synthetic antimicrobial peptides, TRAIL and NRP1 blocking peptides in the pathogenesis and treatment of psoriasis.

Ape1/Ref-1 Stimulates GDNF/GFRα1-mediated Downstream Signaling and Neuroblastoma Proliferation

강미영,김권영,윤영,강윤성,김홍범,윤차경,김동휘,김미화 대한약리학회 2009 The Korean Journal of Physiology & Pharmacology Vol.13 No.5

We previously reported that glial cell line-derived neurotropic factor (GDNF) receptor α1 (GFRα1) is a direct target of apurinic/apyrimidinic endonuclease 1 (Ape1/Ref-1). In the present study, we further analyzed the physiological roles of Ape1/Ref-1-induced GFRα1 expression in Neuro2a mouse neuroblastoma cells. Ape1/Ref-1 expression caused the clustering of GFRα1 immunoreactivity in lipid rafts in response to GDNF. We also found that Ret, a downstream target of GFRα1, was functionally activated by GDNF in Ape1/Ref-1-expressing cells. Moreover, GDNF promoted the proliferation of Ape1/Ref-1-expressing Neuro2a cells. Furthermore, GFRα1-specific RNA experiments demonstrated that the downregulation of GFRα1 by siRNA in Ape1/Ref-1-expressing cells impaired the ability of GDNF to phosphorylate Akt and PLCγ-1 and to stimulate cellular proliferation. These results show an association between Ape1/Ref-1 and GDNF/GFRα signaling, and suggest a potential molecular mechanism for the involvement of Ape1/Ref-1 in neuronal proliferation.

Scavenger Receptor Class A to E Involved in Various Cancers

류순효,Amanda Howland,Brendon Song,윤차경,Peter I Song 전남대학교 의과학연구소 2020 전남의대학술지 Vol.56 No.1

Scavenger receptors typically bind to multiple ligands on a cell surface, including endogenous and modified host-derived molecules and microbial pathogens. They promote the elimination of degraded or harmful substances such as non-self or altered-self targets through endocytosis, phagocytosis, and adhesion. Currently, scavenger receptors are subdivided into eight classes based on several variations in their sequences due to alternative splicing. Since recent studies indicate targeting scavenger receptors has been involved in cancer prognosis and carcinogenesis, we will focus on the current knowledge about the emerging role of scavenger receptor classes A to E in cancer progression.

APEX-1 Regulates Cell Proliferation through GDNF/ GFRα1 Signaling

Hong-Beum Kim(김홍범),Gurusamy Hariharasudhan(구루사미 하리하라수단),Cha-Kyung Youn(윤차경) 한국생명과학회 2013 생명과학회지 Vol.23 No.10

APEX-1 (인간 apyrimidinic / apurinic 효소)은 염기성 사이트 및 DNA단일 가닥 결손으로 손상된 DNA을 복구 할 수 있는 다기능 단백질이다. 또한 APEX-1은 많은 전사 인자들의 redox-modifying factor (산화 환원 수정 요소)로서의 역할을 한다고 알려져 있다. 이런 APEX-1의 전사 타겟을 동정하는 것은 APEX-1의 다양한 세포 내 작용 메커니즘을 이해하는데 필수적이다. 따라서 이 논문에서는 먼저 Expression array analysis를 통해 glial cell-derived neurotropic factor receptor α1 (GFRα1)을 동정하였다. GFRα1은 glial cell-derived neurotropic factor (GDNF) family 수용체이며 APEX-1에 의해 발현이 증가된다. APEX-1이 과발현된 세포에서 GDNF처리에 의해GDNF/ GFRα1 시그널 타겟인 c-Src가 Tyr418잔기에서 인산화 됨을 관찰하였다. 또한 APEX-1이 과발현된 세포에 GDNF처리하면, 세포증식이 증가함을 보았다. 반면, APEX-1 발현을 siRNA을 이용하여 감소시키면 GFR α1 발현과 GDNF에 의한 c-Src 인산화 및 세포증식이 감소함을 확인하였다. 이상의 결과는 APEX-1은 GDNF/GFRα1 시그널을 통해 세포 생존과 증식을 조절함을 증명하였다. 따라서 본 연구를 통해 APEX-1의 세포 증식을 조절하는 새로운 기전을 규명하였다. Human apurinic/apyrimidinic endonuclease (APEX-1) is a multifunctional protein that is capable of repairing abasic sites and single-strand breaks in damaged DNA. In addition, it serves as a redox-modifying factor for a number of transcription factors. Identifying the transcriptional targets of APEX-1 is essential for understanding how it affects various cellular outcomes. Expression array analysis was used to identify glial cell-derived neurotropic factor receptor α1 (GFRα1), which is an encoding receptor for the glial cell-derived neurotropic factor (GDNF) family, the expression of which is induced by APEX-1. A target of GDNF/GFRα signaling, c-Src (Tyr418) was strongly phosphorylated by GNDF in the APEX-1 expressing cells. Moreover, GDNF initiated cell proliferation, measured by counting the number of cells, in the APEX-1 expressing cells. Importantly, the down-regulation of APEX-1 by siRNA caused a marked reduction in the GFRα1 expression level, and it reduced the ability of GDNF to phosphorylate c-Src (Tyr418) and stimulate cell proliferation. These results demonstrate an association between APEX-1 and GDNF/GFRα signaling and suggest a potential molecular mechanism for the involvement of APEX-1 in cell survival and proliferation.