Korean Journal of Physiology & Pharmacology最新文献_第8页

Somatodendritic organization of pacemaker activity in midbrain dopamine neurons. 中脑多巴胺神经元起搏器活动的躯体树突组织

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2024-03-01 DOI: 10.4196/kjpp.2024.28.2.165

Jinyoung Jang, Shin Hye Kim, Ki Bum Um, Hyun Jin Kim, Myoung Kyu Park

{"title":"Somatodendritic organization of pacemaker activity in midbrain dopamine neurons.","authors":"Jinyoung Jang, Shin Hye Kim, Ki Bum Um, Hyun Jin Kim, Myoung Kyu Park","doi":"10.4196/kjpp.2024.28.2.165","DOIUrl":"10.4196/kjpp.2024.28.2.165","url":null,"abstract":"The slow and regular pacemaking activity of midbrain dopamine (DA) neurons requires proper spatial organization of the excitable elements between the soma and dendritic compartments, but the somatodendritic organization is not clear. Here, we show that the dynamic interaction between the soma and multiple proximal dendritic compartments (PDCs) generates the slow pacemaking activity in DA neurons. In multipolar DA neurons, spontaneous action potentials (sAPs) consistently originate from the axon-bearing dendrite. However, when the axon initial segment was disabled, sAPs emerge randomly from various primary PDCs, indicating that multiple PDCs drive pacemaking. Ca2+ measurements and local stimulation/perturbation experiments suggest that the soma serves as a stably-oscillating inertial compartment, while multiple PDCs exhibit stochastic fluctuations and high excitability. Despite the stochastic and excitable nature of PDCs, their activities are balanced by the large centrally-connected inertial soma, resulting in the slow synchronized pacemaking rhythm. Furthermore, our electrophysiological experiments indicate that the soma and PDCs, with distinct characteristics, play different roles in glutamate- induced burst-pause firing patterns. Excitable PDCs mediate excitatory burst responses to glutamate, while the large inertial soma determines inhibitory pause responses to glutamate. Therefore, we could conclude that this somatodendritic organization serves as a common foundation for both pacemaker activity and evoked firing patterns in midbrain DA neurons.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 2","pages":"165-181"},"PeriodicalIF":2.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10902590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139984544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transcriptional regulation of genetic variants in the SLC40A1 promoter. SLC40A1 启动子中遗传变异的转录调控。

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2024-03-01 DOI: 10.4196/kjpp.2024.28.2.113

Seung Yeon Ha, Jin-Young Kim, Ji Ha Choi

{"title":"Transcriptional regulation of genetic variants in the SLC40A1 promoter.","authors":"Seung Yeon Ha, Jin-Young Kim, Ji Ha Choi","doi":"10.4196/kjpp.2024.28.2.113","DOIUrl":"10.4196/kjpp.2024.28.2.113","url":null,"abstract":"Solute carrier 40A1 (SLC40A1) encodes ferroportin, which is the only known transmembrane protein that exports elemental iron from mammalian cells and is essential for iron homeostasis. Mutations in SLC40A1 are associated with iron-overload disorders. In addition to ferroportin diseases, SLC40A1 expression is downregulated in various cancer types. Despite the clinical significance of the SLC40A1 transporter, only a few studies have investigated genetic variants in SLC40A1. The present study was performed to identify genetic variations in the SLC40A1 promoter and functionally characterize each variant using in vitro assays. We investigated four haplotypes and five variants in the SLC40A1 promoter. We observed that haplotype 3 (H3) had significantly lower promoter activity than H1, whereas the activity of H4 was significantly higher than that of H1. Luciferase activity of H2 was comparable to that of H1. In addition, four variants of SLC40A1, c.-1355G>C, c.-662C>T, c.-98G>C, and c.-8C>G, showed significantly increased luciferase activity compared to the wild type (WT), whereas c.-750G>A showed significantly decreased luciferase activity compared to the WT. Three transcription factors, cAMP response element-binding protein-1 (CREB-1), chicken ovalbumin upstream promoter transcription factor 1, and hepatic leukemia factor (HLF), were predicted to bind to the promoter regions of SLC40A1 near c.-662C>T, c.-98G>C, and c.-8C>G, respectively. Among these, CREB-1 and HLF bound more strongly to the variant sequences than to the WT and functioned as activators of SLC40A1 transcription. Collectively, our findings indicate that the two SLC40A1 promoter haplotypes affect SLC40A1 transcription, which is regulated by CREB-1 and HLF.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 2","pages":"113-120"},"PeriodicalIF":2.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10902591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139984546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of 27-hydroxycholesterol in meta-inflammation. 27- 羟基胆固醇在元炎症中的作用。

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2024-03-01 DOI: 10.4196/kjpp.2024.28.2.107

Yonghae Son, Eunbeen Choi, Yujin Hwang, Koanhoi Kim

{"title":"The role of 27-hydroxycholesterol in meta-inflammation.","authors":"Yonghae Son, Eunbeen Choi, Yujin Hwang, Koanhoi Kim","doi":"10.4196/kjpp.2024.28.2.107","DOIUrl":"10.4196/kjpp.2024.28.2.107","url":null,"abstract":"27-Hydroxycholesterol (27OHChol), a prominent cholesterol metabolite present in the bloodstream and peripheral tissues, is a kind of immune oxysterol that elicits immune response. Recent research indicates the involvement of 27OHChol in metabolic inflammation (meta-inflammation) characterized by chronic responses associated with metabolic irregularities. 27OHChol activates monocytic cells such that they secrete pro-inflammatory cytokines and chemokines, and increase the expression of cell surface molecules such as pattern-recognition receptors that play key roles in immune cell-cell communication and sensing metabolism-associated danger signals. Levels of 27OHChol increase when cholesterol metabolism is disrupted, and the resulting inflammatory responses can contribute to the development and complications of metabolic syndrome, including obesity, insulin resistance, and cardiovascular diseases. Since 27OHChol can induce chronic immune response by activating monocyte-macrophage lineage cells that play a crucial role in meta-inflammation, it is essential to understand the 27OHChol-induced inflammatory responses to unravel the roles and mechanisms of action of this cholesterol metabolite in chronic metabolic disorders.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 2","pages":"107-112"},"PeriodicalIF":2.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10902588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139984545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of a model to predict vancomycin serum concentration during continuous infusion of vancomycin in critically ill pediatric patients. 开发一种模型，用于预测重症儿科患者持续输注万古霉素期间的万古霉素血清浓度。

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2024-03-01 DOI: 10.4196/kjpp.2024.28.2.121

Yu Jin Han, Wonjin Jang, Jung Sun Kim, Hyun Jeong Kim, Sung Yun Suh, Yoon Sook Cho, June Dong Park, Bongjin Lee

{"title":"Development of a model to predict vancomycin serum concentration during continuous infusion of vancomycin in critically ill pediatric patients.","authors":"Yu Jin Han, Wonjin Jang, Jung Sun Kim, Hyun Jeong Kim, Sung Yun Suh, Yoon Sook Cho, June Dong Park, Bongjin Lee","doi":"10.4196/kjpp.2024.28.2.121","DOIUrl":"10.4196/kjpp.2024.28.2.121","url":null,"abstract":"Vancomycin is a frequently used antibiotic in intensive care units, and the patient's renal clearance affects the pharmacokinetic characteristics of vancomycin. Several advantages have been reported for vancomycin continuous intravenous infusion, but studies on continuous dosing regimens based on patients' renal clearance are insufficient. The aim of this study was to develop a vancomycin serum concentration prediction model by factoring in a patient's renal clearance. Children admitted to our institution between July 1, 2021, and July 31, 2022 with records of continuous infusion of vancomycin were included in the study. Sex, age, height, weight, vancomycin dose by weight, interval from the start of vancomycin administration to the time of therapeutic drug monitoring sampling, and vancomycin serum concentrations were analyzed with the linear regression analysis of the mixed effect model. Univariable regression analysis was performed using the vancomycin serum concentration as a dependent variable. It showed that vancomycin dose (p < 0.001) and serum creatinine (p = 0.007) were factors that had the most impact on vancomycin serum concentration. Vancomycin serum concentration was affected by vancomycin dose (p < 0.001) and serum creatinine (p = 0.001) with statistical significance, and a multivariable regression model was obtained as follows: Vancomycin serum concentration (mg/l) = -1.296 + 0.281 × vancomycin dose (mg/kg) + 20.458 × serum creatinine (mg/dl) (adjusted coefficient of determination, R2 = 0.66). This prediction model is expected to contribute to establishing an optimal continuous infusion regimen for vancomycin.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 2","pages":"121-127"},"PeriodicalIF":2.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10902586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139984540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lithium and exercise ameliorate insulin-deficient hyperglycemia by independently attenuating pancreatic α-cell mass and hepatic gluconeogenesis. 锂和运动可通过独立减轻胰腺α细胞质量和肝脏葡萄糖生成来改善胰岛素缺乏性高血糖症。

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2024-01-01 DOI: 10.4196/kjpp.2024.28.1.31

Su-Ryun Jung, Ji-Hye Lee, Hanguk Ryu, Yurong Gao, Jaemin Lee

{"title":"Lithium and exercise ameliorate insulin-deficient hyperglycemia by independently attenuating pancreatic α-cell mass and hepatic gluconeogenesis.","authors":"Su-Ryun Jung, Ji-Hye Lee, Hanguk Ryu, Yurong Gao, Jaemin Lee","doi":"10.4196/kjpp.2024.28.1.31","DOIUrl":"10.4196/kjpp.2024.28.1.31","url":null,"abstract":"As in type 1 diabetes, the loss of pancreatic β-cells leads to insulin deficiency and the subsequent development of hyperglycemia. Exercise has been proposed as a viable remedy for hyperglycemia. Lithium, which has been used as a treatment for bipolar disorder, has also been shown to improve glucose homeostasis under the conditions of obesity and type 2 diabetes by enhancing the effects of exercise on the skeletal muscles. In this study, we demonstrated that unlike in obesity and type 2 diabetic conditions, under the condition of insulin-deficient type 1 diabetes, lithium administration attenuated pancreatic a-cell mass without altering insulin-secreting β-cell mass, implying a selective impact on glucagon production. Additionally, we also documented that lithium downregulated the hepatic gluconeogenic program by decreasing G6Pase protein levels and upregulating AMPK activity. These findings suggest that lithium's effect on glucose metabolism in type 1 diabetes is mediated through a different mechanism than those associated with exerciseinduced metabolic changes in the muscle. Therefore, our research presents the novel therapeutic potential of lithium in the treatment of type 1 diabetes, which can be utilized along with insulin and independently of exercise.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 1","pages":"31-38"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139059150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Wogonin attenuates vascular remodeling by inhibiting smooth muscle cell proliferation and migration in hypertensive rat. 五倍子苷通过抑制高血压大鼠平滑肌细胞的增殖和迁移，减轻血管重塑。

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2024-01-01 DOI: 10.4196/kjpp.2024.28.1.39

Yang Yang, Shan Huang, Jun Wang, Xiao Nie, Ling Huang, Tianfa Li

{"title":"Wogonin attenuates vascular remodeling by inhibiting smooth muscle cell proliferation and migration in hypertensive rat.","authors":"Yang Yang, Shan Huang, Jun Wang, Xiao Nie, Ling Huang, Tianfa Li","doi":"10.4196/kjpp.2024.28.1.39","DOIUrl":"10.4196/kjpp.2024.28.1.39","url":null,"abstract":"Wogonin, extracted from the roots of Scutellaria baicalensis Georgi, has been shown to suppress collagen deposition in spontaneously hypertensive rats (SHRs). This study was performed to investigate the role and mechanism of wogonin underlying vascular remodeling in SHRs. After injection of SHRs with 40 mg/kg of wogonin, blood pressure in rats was measured once a week. Masson's trichrome staining was conducted to observe the changes in aortas and mesenteric arteries. Vascular smooth muscle cells (VSMCs) isolated from rat thoracic aortas were treated with Angiotensin II (Ang II; 100 nM) in the presence or absence of varying concentrations of wogonin. The viability and proliferation of VSMCs were examined using Cell Counting Kit-8 assay and 5-ethynyl-2'-deoxyuridine assay, respectively. The migration of VSMCs was examined using wound healing assay and transwell assay. We found that wogonin administration alleviated hypertension, increased lumen diameter, and reduced the thickness of the arterial media in SHRs. Ang II treatment enhanced the viability of VSMCs, which was inhibited by wogonin in a concentration-dependent manner. Wogonin reversed Ang II-induced increases in the viability, proliferation, and migration of VSMCs. Moreover, wogonin inhibited Ang II-induced activation of mitogen-activated protein kinase (MAPK) signaling in VSMCs. Overall, wogonin repressed the proliferative and migratory capacity of VSMCs by regulating the MAPK signaling pathway, thereby attenuating vascular remodeling in hypertensive rats, indicating that wogonin might be a therapeutic agent for the treatment of vascular diseases.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 1","pages":"39-48"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139059154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Differential expression of the enzymes regulating myosin light chain phosphorylation are responsible for the slower relaxation of pulmonary artery than mesenteric artery in rats. 调节肌球蛋白轻链磷酸化的酶的不同表达是导致大鼠肺动脉松弛慢于肠系膜动脉的原因。

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2024-01-01 DOI: 10.4196/kjpp.2024.28.1.49

Seung Beom Oh, Suhan Cho, Hyun Jong Kim, Sung Joon Kim

{"title":"Differential expression of the enzymes regulating myosin light chain phosphorylation are responsible for the slower relaxation of pulmonary artery than mesenteric artery in rats.","authors":"Seung Beom Oh, Suhan Cho, Hyun Jong Kim, Sung Joon Kim","doi":"10.4196/kjpp.2024.28.1.49","DOIUrl":"10.4196/kjpp.2024.28.1.49","url":null,"abstract":"While arterial tone is generally determined by the phosphorylation of Ser19 in myosin light chain (p-MLC2), Thr18/Ser19 diphosphorylation of MLC2 (pp-MLC2) has been suggested to hinder the relaxation of smooth muscle. In a dual-wire myography of rodent pulmonary artery (PA) and mesenteric artery (MA), we noticed significantly slower relaxation in PA than in MA after 80 mM KCl-induced condition (80K-contraction). Thus, we investigated the MLC2 phosphorylation and the expression levels of its regulatory enzymes; soluble guanylate cyclase (sGC), Rho-A dependent kinase (ROCK) and myosin light chain phosphatase target regulatory subunit (MYPT1). Immunoblotting showed higher sGC-α and ROCK2 in PA than MA, while sGC-β and MYPT1 levels were higher in MA than in PA. Interestingly, the level of pp-MLC2 was higher in PA than in MA without stimulation. In the 80K-contraction state, the levels of p-MLC2 and pp-MLC2 were commonly increased. Treatment with the ROCK inhibitor (Y27632, 10 μM) reversed the higher pp-MLC2 in PA. In the myography study, pharmacological inhibition of sGC (ODQ, 10 μM) slowed relaxation during washout, which was more pronounced in PA than in MA. The simultaneous treatment of Y27632 and ODQ reversed the impaired relaxation in PA and MA. Although treatment of PA with Y27632 alone could increase the rate of relaxation, it was still slower than that of MA without Y27632 treatment. Taken together, we suggest that the higher ROCK and lower MYPT in PA would have induced the higher level of MLC2 phosphorylation, which is responsible for the characteristic slow relaxation in PA.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 1","pages":"49-57"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139059148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Naringenin modulates GABA mediated response in a sexdependent manner in substantia gelatinosa neurons of trigeminal subnucleus caudalis in immature mice. 柚皮素以性别依赖的方式调节未成熟小鼠三叉神经尾下核胶质神经元的GABA介导反应

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2024-01-01 DOI: 10.4196/kjpp.2024.28.1.73

Seon Ah Park, Thao Thi Phuong Nguyen, Soo Joung Park, Seong Kyu Han

{"title":"Naringenin modulates GABA mediated response in a sexdependent manner in substantia gelatinosa neurons of trigeminal subnucleus caudalis in immature mice.","authors":"Seon Ah Park, Thao Thi Phuong Nguyen, Soo Joung Park, Seong Kyu Han","doi":"10.4196/kjpp.2024.28.1.73","DOIUrl":"10.4196/kjpp.2024.28.1.73","url":null,"abstract":"The substantia gelatinosa (SG) within the trigeminal subnucleus caudalis (Vc) is recognized as a pivotal site of integrating and modulating afferent fibers carrying orofacial nociceptive information. Although naringenin (4',5,7-thrihydroxyflavanone), a natural bioflavonoid, has been proven to possess various biological effects in the central nervous system (CNS), the activity of naringenin at the orofacial nociceptive site has not been reported yet. In this study, we explored the influence of naringenin on GABA response in SG neurons of Vc using whole-cell patch-clamp technique. The application of GABA in a bath induced two forms of GABA responses: slow and fast. Naringenin enhanced both amplitude and area under curve (AUC) of GABA-mediated responses in 57% (12/21) of tested neurons while decreasing both parameters in 33% (7/21) of neurons. The enhancing or suppressing effect of naringenin on GABA response have been observed, with enhancement occurring when the GABA response was slow, and suppression when it was fast. Furthermore, both the enhancement of slower GABA responses and the suppression of faster GABA responses by naringenin were concentration dependent. Interestingly, the nature of GABA response was also found to be sex-dependent. A majority of SG neurons from juvenile female mice exhibited slower GABA responses, whereas those from juvenile males predominantly displayed faster GABA responses. Taken together, this study indicates that naringenin plays a partial role in modulating orofacial nociception and may hold promise as a therapeutic target for treating orofacial pain, with effects that vary according to sex.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 1","pages":"73-81"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139059152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ACY-241, a histone deacetylase 6 inhibitor, suppresses the epithelial-mesenchymal transition in lung cancer cells by downregulating hypoxia-inducible factor-1 alpha. 组蛋白去乙酰化酶 6 抑制剂 ACY-241 通过下调缺氧诱导因子-1 alpha 抑制肺癌细胞的上皮-间质转化。

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2024-01-01 DOI: 10.4196/kjpp.2024.28.1.83

Seong-Jun Park, Naeun Lee, Chul-Ho Jeong

{"title":"ACY-241, a histone deacetylase 6 inhibitor, suppresses the epithelial-mesenchymal transition in lung cancer cells by downregulating hypoxia-inducible factor-1 alpha.","authors":"Seong-Jun Park, Naeun Lee, Chul-Ho Jeong","doi":"10.4196/kjpp.2024.28.1.83","DOIUrl":"10.4196/kjpp.2024.28.1.83","url":null,"abstract":"Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor activated under hypoxic conditions, and it plays a crucial role in cellular stress regulation. While HIF-1α activity is essential in normal tissues, its presence in the tumor microenvironment represents a significant risk factor as it can induce angiogenesis and confer resistance to anti-cancer drugs, thereby contributing to poor prognoses. Typically, HIF-1α undergoes rapid degradation in normoxic conditions via oxygen-dependent degradation mechanisms. However, certain cancer cells can express HIF-1α even under normoxia. In this study, we observed an inclination toward increased normoxic HIF-1α expression in cancer cell lines exhibiting increased HDAC6 expression, which prompted the hypothesis that HDAC6 may modulate HIF-1α stability in normoxic conditions. To prove this hypothesis, several cancer cells with relatively higher HIF-1α levels under normoxic conditions were treated with ACY-241, a selective HDAC6 inhibitor, and small interfering RNAs for HDAC6 knockdown. Our data revealed a significant reduction in HIF-1α expression upon HDAC6 inhibition. Moreover, the downregulation of HIF-1α under normoxic conditions decreased zinc finger E-box-binding homeobox 1 expression and increased E-cadherin levels in lung cancer H1975 cells, consequently suppressing cell invasion and migration. ACY-241 treatment also demonstrated an inhibitory effect on cell invasion and migration by reducing HIF-1α level. This study confirms that HDAC6 knockdown and ACY-241 treatment effectively decrease HIF-1α expression under normoxia, thereby suppressing the epithelial-mesenchymal transition. These findings highlight the potential of selective HDAC6 inhibition as an innovative therapeutic strategy for lung cancer.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 1","pages":"83-91"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139059145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mechanism of Wenshen Xuanbi Decoction in the treatment of osteoarthritis based on network pharmacology and experimental verification. 基于网络药理学和实验验证的温神宣肺汤治疗骨关节炎的机理。

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2024-01-01 DOI: 10.4196/kjpp.2024.28.1.59

Hankun You, Siyuan Song, Deren Liu, Tongsen Ren, Song Jiang Yin, Peng Wu, Jun Mao

{"title":"Mechanism of Wenshen Xuanbi Decoction in the treatment of osteoarthritis based on network pharmacology and experimental verification.","authors":"Hankun You, Siyuan Song, Deren Liu, Tongsen Ren, Song Jiang Yin, Peng Wu, Jun Mao","doi":"10.4196/kjpp.2024.28.1.59","DOIUrl":"10.4196/kjpp.2024.28.1.59","url":null,"abstract":"To investigate the mechanism of Wenshen Xuanbi Decoction (WSXB) in treating osteoarthritis (OA) via network pharmacology, bioinformatics analysis, and experimental verification. The active components and prediction targets of WSXB were obtained from the TCMSP database and Swiss Target Prediction website, respectively. OA-related genes were retrieved from GeneCards and OMIM databases. Protein-protein interaction and functional enrichment analyses were performed, resulting in the construction of the Herb-Component-Target network. In addition, differential genes of OA were obtained from the GEO database to verify the potential mechanism of WSXB in OA treatment. Subsequently, potential active components were subjected to molecular verification with the hub targets. Finally, we selected the most crucial hub targets and pathways for experimental verification in vitro. The active components in the study included quercetin, linolenic acid, methyl linoleate, isobergapten, and beta-sitosterol. AKT1, tumor necrosis factor (TNF), interleukin (IL)-6, GAPDH, and CTNNB1 were identified as the most crucial hub targets. Molecular docking revealed that the active components and hub targets exhibited strong binding energy. Experimental verification demonstrated that the mRNA and protein expression levels of IL-6, IL-17, and TNF in the WSXB group were lower than those in the KOA group (p < 0.05). WSXB exhibits a chondroprotective effect on OA and delays disease progression. The mechanism is potentially related to the suppression of IL-17 and TNF signaling pathways and the down-regulation of IL-6.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 1","pages":"59-72"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139059151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0