Korean Journal of Physiology & Pharmacology最新文献_第9页

Inhibition of Wnt/β-catenin signaling by monensin in cervical cancer. 莫能菌素抑制宫颈癌中的 Wnt/β-catenin 信号传导

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2024-01-01 DOI: 10.4196/kjpp.2024.28.1.21

Bingbing Fu, Lixia Fang, Ranran Wang, Xueling Zhang

{"title":"Inhibition of Wnt/β-catenin signaling by monensin in cervical cancer.","authors":"Bingbing Fu, Lixia Fang, Ranran Wang, Xueling Zhang","doi":"10.4196/kjpp.2024.28.1.21","DOIUrl":"10.4196/kjpp.2024.28.1.21","url":null,"abstract":"The challenging clinical outcomes associated with advanced cervical cancer underscore the need for a novel therapeutic approach. Monensin, a polyether antibiotic, has recently emerged as a promising candidate with anti-cancer properties. In line with these ongoing efforts, our study presents compelling evidence of monensin's potent efficacy in cervical cancer. Monensin exerts a pronounced inhibitory impact on proliferation and anchorage-independent growth. Additionally, monensin significantly inhibited cervical cancer growth in vivo without causing any discernible toxicity in mice. Mechanism studies show that monensin's anti-cervical cancer activity can be attributed to its capacity to inhibit the Wnt/β-catenin pathway, rather than inducing oxidative stress. Monensin effectively reduces both the levels and activity of β-catenin, and we identify Akt, rather than CK1, as the key player involved in monensin-mediated Wnt/β-catenin inhibition. Rescue studies using Wnt activator and β-catenin-overexpressing cells confirmed that β-catenin inhibition is the mechanism of monensin's action. As expected, cervical cancer cells exhibiting heightened Wnt/β-catenin activity display increased sensitivity to monensin treatment. In conclusion, our findings provide pre-clinical evidence that supports further exploration of monensin's potential for repurposing in cervical cancer therapy, particularly for patients exhibiting aberrant Wnt/β-catenin activation.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 1","pages":"21-30"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139059149","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

Aurantio-obtusin exerts an anti-inflammatory effect on acute kidney injury by inhibiting NF-κB pathway. 橙黄决明素通过抑制 NF-κB 通路对急性肾损伤产生抗炎作用。

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2024-01-01 DOI: 10.4196/kjpp.2024.28.1.11

Haiyan Xiang, Yun Zhang, Yan Wu, Yaling Xu, Yuanhao Hong

{"title":"Aurantio-obtusin exerts an anti-inflammatory effect on acute kidney injury by inhibiting NF-κB pathway.","authors":"Haiyan Xiang, Yun Zhang, Yan Wu, Yaling Xu, Yuanhao Hong","doi":"10.4196/kjpp.2024.28.1.11","DOIUrl":"10.4196/kjpp.2024.28.1.11","url":null,"abstract":"Acute kidney injury (AKI) is one of the major complications of sepsis. Aurantio-obtusin (AO) is an anthraquinone compound with antioxidant and anti-inflammatory activities. This study was developed to concentrate on the role and mechanism of AO in sepsis-induced AKI. Lipopolysaccharide (LPS)-stimulated human renal proximal tubular epithelial cells (HK-2) and BALB/c mice receiving cecal ligation and puncture (CLP) surgery were used to establish in vitro cell model and in vivo mouse model. HK-2 cell viability was measured using MTT assays. Histological alterations of mouse renal tissues were analyzed via hematoxylin and eosin staining. Renal function of mice was assessed by measuring the levels of serum creatinine (SCr) and blood urea nitrogen (BUN). The concentrations of pro-inflammatory cytokines in HK-2 cells and serum samples of mice were detected using corresponding ELISA kits. Protein levels of factors associated with nuclear factor kappa-B (NF-κB) pathway were measured in HK-2 cells and renal tissues by Western blotting. AO exerted no cytotoxic effect on HK-2 cells and AO dose-dependently rescued LPS-induced decrease in HK-2 cell viability. The concentrations of pro-inflammatory cytokines were increased in response to LPS or CLP treatment, and the alterations were reversed by AO treatment. For in vivo experiments, AO markedly ameliorated renal injury and reduced high levels of SCr and BUN in mice underwent CLP operation. In addition, AO administration inhibited the activation of NF-κB signaling pathway in vitro and in vivo. In conclusion, AO alleviates septic AKI by suppressing inflammatory responses through inhibiting the NF-κB pathway.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 1","pages":"11-19"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139059146","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

Carvacrol improves blood lipid and glucose in rats with type 2 diabetes mellitus by regulating short-chain fatty acids and the GPR41/43 pathway. 香芹酚通过调节短链脂肪酸和 GPR41/43 通路改善 2 型糖尿病大鼠的血脂和血糖。

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2024-01-01 DOI: 10.4196/kjpp.2024.28.1.1

Yan Sun, Hai Qu, Xiaohong Niu, Ting Li, Lijuan Wang, Hairui Peng

{"title":"Carvacrol improves blood lipid and glucose in rats with type 2 diabetes mellitus by regulating short-chain fatty acids and the GPR41/43 pathway.","authors":"Yan Sun, Hai Qu, Xiaohong Niu, Ting Li, Lijuan Wang, Hairui Peng","doi":"10.4196/kjpp.2024.28.1.1","DOIUrl":"10.4196/kjpp.2024.28.1.1","url":null,"abstract":"Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia and dyslipidemia. Carvacrol (CAR) has demonstrated the potential to mitigate dyslipidemia. This study aims to investigate whether CAR can modulate blood glucose and lipid levels in a T2DM rat model by regulating short-chain fatty acids (SCFAs) and the GPR41/43 pathway. The T2DM rat model was induced by a high-fat diet combined with low-dose streptozocin injection and treated with oral CAR and/or mixed antibiotics. Fasting blood glucose, oral glucose tolerance, and insulin tolerance tests were assessed. Serum lipid parameters, hepatic and renal function indicators, tissue morphology, and SCFAs were measured. In vitro, high glucose (HG)-induced IEC-6 cells were treated with CAR, and optimal CAR concentration was determined. HG-induced IEC-6 cells were treated with SCFAs or/and GPR41/43 agonists. CAR significantly reduced blood lipid and glucose levels, improved tissue damage, and increased SCFA levels in feces and GPR41/43 expression in colonic tissues of T2DM rats. CAR also attenuated HG-induced apoptosis of IEC-6 cells and enhanced GPR41/43 expression. Overall, these findings suggest that CAR alleviates blood lipid and glucose abnormalities in T2DM rats by modulating SCFAs and the GPR41/43 pathway.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 1","pages":"1-10"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139059147","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

Store-operated calcium entry in the satellite glial cells of rat sympathetic ganglia. 大鼠交感神经节卫星神经胶质细胞中的储能钙离子通道

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2024-01-01 DOI: 10.4196/kjpp.2024.28.1.93

Sohyun Kim, Seong Jun Kang, Huu Son Nguyen, Seong-Woo Jeong

{"title":"Store-operated calcium entry in the satellite glial cells of rat sympathetic ganglia.","authors":"Sohyun Kim, Seong Jun Kang, Huu Son Nguyen, Seong-Woo Jeong","doi":"10.4196/kjpp.2024.28.1.93","DOIUrl":"10.4196/kjpp.2024.28.1.93","url":null,"abstract":"Satellite glial cells (SGCs), a major type of glial cell in the autonomic ganglia, closely envelop the cell body and even the synaptic regions of a single neuron with a very narrow gap. This structurally unique organization suggests that autonomic neurons and SGCs may communicate reciprocally. Glial Ca2+ signaling is critical for controlling neural activity. Here, for the first time we identified the machinery of store-operated Ca2+ entry (SOCE) which is critical for cellular Ca2+ homeostasis in rat sympathetic ganglia under normal and pathological states. Quantitative realtime PCR and immunostaining analyses showed that Orai1 and stromal interaction molecules 1 (STIM1) proteins are the primary components of SOCE machinery in the sympathetic ganglia. When the internal Ca2+ stores were depleted in the absence of extracellular Ca2+, the number of plasmalemmal Orai1 puncta was increased in neurons and SGCs, suggesting activation of the Ca2+ entry channels. Intracellular Ca2+ imaging revealed that SOCE was present in SGCs and neurons; however, the magnitude of SOCE was much larger in the SGCs than in the neurons. The SOCE was significantly suppressed by GSK7975A, a selective Orai1 blocker, and Pyr6, a SOCE blocker. Lipopolysaccharide (LPS) upregulated the glial fibrillary acidic protein and Toll-like receptor 4 in the sympathetic ganglia. Importantly, LPS attenuated SOCE via downregulating Orai1 and STIM1 expression. In conclusion, sympathetic SGCs functionally express the SOCE machinery, which is indispensable for intracellular Ca2+ signaling. The SOCE is highly susceptible to inflammation, which may affect sympathetic neuronal activity and thereby autonomic output.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 1","pages":"93-103"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139059153","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

Multiple consecutive-biphasic pulse stimulation improves spatially localized firing of retinal ganglion cells in the degenerate retina. 多个连续的双相脉冲刺激改善了退化视网膜中视网膜神经节细胞的空间局部放电。

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2023-11-01 DOI: 10.4196/kjpp.2023.27.6.541

Jungryul Ahn, Yongseok Yoo, Yong Sook Goo

{"title":"Multiple consecutive-biphasic pulse stimulation improves spatially localized firing of retinal ganglion cells in the degenerate retina.","authors":"Jungryul Ahn, Yongseok Yoo, Yong Sook Goo","doi":"10.4196/kjpp.2023.27.6.541","DOIUrl":"10.4196/kjpp.2023.27.6.541","url":null,"abstract":"Retinal prostheses have shown some clinical success in restoring vision in patients with retinitis pigmentosa. However, the post-implantation visual acuity does not exceed that of legal blindness. The reason for the poor visual acuity might be that (1) degenerate retinal ganglion cells (RGCs) are less responsive to electrical stimulation than normal RGCs, and (2) electrically-evoked RGC spikes show a more widespread not focal response. The single-biphasic pulse electrical stimulation, commonly used in artificial vision, has limitations in addressing these issues. In this study, we propose the benefit of multiple consecutive-biphasic pulse stimulation. We used C57BL/6J mice and C3H/HeJ (rd1) mice for the normal retina and retinal degeneration model. An 8 × 8 multi-electrode array was used to record electrically-evoked RGC spikes. We compared RGC responses when increasing the amplitude of a single biphasic pulse versus increasing the number of consecutive biphasic pulses at the same stimulus charge. Increasing the amplitude of a single biphasic pulse induced more RGC spike firing while the spatial resolution of RGC populations decreased. For multiple consecutive-biphasic pulse stimulation, RGC firing increased as the number of pulses increased, and the spatial resolution of RGC populations was well preserved even up to 5 pulses. Multiple consecutive-biphasic pulse stimulation using two or three pulses in degenerate retinas induced as much RGC spike firing as in normal retinas. These findings suggest that the newly proposed multiple consecutive-biphasic pulse stimulation can improve the visual acuity in prosthesis-implanted patients.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"27 6","pages":"541-553"},"PeriodicalIF":2.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10613570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54232353","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

Three sesquiterpene lactones suppress lung adenocarcinoma by blocking TMEM16A-mediated Ca²⁺-activated Cl^- channels. 三种倍半萜内酯通过阻断TMEM16A介导的Ca2+激活的Cl-通道来抑制肺腺癌。

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2023-11-01 DOI: 10.4196/kjpp.2023.27.6.521

Ruilian Xiu, Jie Jia, Qing Zhang, Fengjiao Liu, Yaxin Jia, Yuanyuan Zhang, Beibei Song, Xiaodan Liu, Jingwei Chen, Dongyang Huang, Fan Zhang, Juanjuan Ma, Honglin Li, Xuan Zhang, Yunyun Geng

{"title":"Three sesquiterpene lactones suppress lung adenocarcinoma by blocking TMEM16A-mediated Ca2+-activated Cl- channels.","authors":"Ruilian Xiu, Jie Jia, Qing Zhang, Fengjiao Liu, Yaxin Jia, Yuanyuan Zhang, Beibei Song, Xiaodan Liu, Jingwei Chen, Dongyang Huang, Fan Zhang, Juanjuan Ma, Honglin Li, Xuan Zhang, Yunyun Geng","doi":"10.4196/kjpp.2023.27.6.521","DOIUrl":"10.4196/kjpp.2023.27.6.521","url":null,"abstract":"Transmembrane protein TMEM16A, which encodes calcium-activated chloride channel has been implicated in tumorigenesis. Overexpression of TMEM16A is associated with poor prognosis and low overall survival in multiple cancers including lung adenocarcinoma, making it a promising biomarker and therapeutic target. In this study, three structure-related sesquiterpene lactones (mecheliolide, costunolide and dehydrocostus lactone) were extracted from the traditional Chinese medicine Aucklandiae Radix and identified as novel TMEM16A inhibitors with comparable inhibitory effects. Their effects on the proliferation and migration of lung adenocarcinoma cells were examined. Whole-cell patch clamp experiments showed that these sesquiterpene lactones potently inhibited recombinant TMEM16A currents in a concentration-dependent manner. The half-maximal concentration (IC50) values for three tested sesquiterpene lactones were 29.9 ± 1.1 μM, 19.7 ± 0.4 μM, and 24.5 ± 2.1 μM, while the maximal effect (Emax) values were 100.0% ± 2.8%, 85.8% ± 0.9%, and 88.3% ± 4.6%, respectively. These sesquiterpene lactones also significantly inhibited the endogenous TMEM16A currents and proliferation, and migration of LA795 lung cancer cells. These results demonstrate that mecheliolide, costunolide and dehydrocostus lactone are novel TMEM16A inhibitors and potential candidates for lung adenocarcinoma therapy.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"27 6","pages":"521-531"},"PeriodicalIF":2.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10613571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54232355","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

Sweroside plays a role in mitigating high glucose-induced damage in human renal tubular epithelial HK-2 cells by regulating the SIRT1/NF-κB signaling pathway. Sweroside通过调节SIRT1/NF-κB信号通路，在减轻高糖诱导的人肾小管上皮HK-2细胞损伤中发挥作用。

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2023-11-01 DOI: 10.4196/kjpp.2023.27.6.533

Xiaodan Ma, Zhixin Guo, Wenhua Zhao, Li Chen

{"title":"Sweroside plays a role in mitigating high glucose-induced damage in human renal tubular epithelial HK-2 cells by regulating the SIRT1/NF-κB signaling pathway.","authors":"Xiaodan Ma, Zhixin Guo, Wenhua Zhao, Li Chen","doi":"10.4196/kjpp.2023.27.6.533","DOIUrl":"10.4196/kjpp.2023.27.6.533","url":null,"abstract":"Sweroside is a natural monoterpene derived from Swertia pseudochinensis Hara. Recently, studies have shown that sweroside exhibits a variety of biological activities, such as anti-inflammatory, antioxidant, and hypoglycemic effects. However, its role and mechanisms in high glucose (HG)-induced renal injury remain unclear. Herein, we established a renal injury model in vitro by inducing human renal tubular epithelial cell (HK-2 cells) injury by HG. Then, the effects of sweroside on HK-2 cell activity, inflammation, reactive oxygen species (ROS) production, and epithelial mesenchymal transition (EMT) were observed. As a result, sweroside treatment ameliorated the viability, inhibited the secretion of inflammatory cytokines (TNF-α, IL-1β, and VCAM-1), reduced the generation of ROS, and inhibited EMT in HK-2 cells. Moreover, the protein expression of SIRT1 was increased and the acetylation of p65 NF-kB was decreased in HK-2 cells with sweroside treatment. More importantly, EX527, an inhibitor of SIRT1, that inactivated SIRT1, abolished the improvement effects of sweroside on HK-2 cells. Our findings suggested that sweroside may mitigate HG-caused injury in HK-2 cells by promoting SIRT1-mediated deacetylation of p65 NF-kB.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"27 6","pages":"533-540"},"PeriodicalIF":2.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10613573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54232354","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

Cornuside inhibits glucose-induced proliferation and inflammatory response of mesangial cells. Cornuside抑制葡萄糖诱导的系膜细胞增殖和炎症反应。

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2023-11-01 DOI: 10.4196/kjpp.2023.27.6.513

Xiaoxin Li, Lizhong Guo, Fei Huang, Wei Xu, Guiqing Peng

{"title":"Cornuside inhibits glucose-induced proliferation and inflammatory response of mesangial cells.","authors":"Xiaoxin Li, Lizhong Guo, Fei Huang, Wei Xu, Guiqing Peng","doi":"10.4196/kjpp.2023.27.6.513","DOIUrl":"10.4196/kjpp.2023.27.6.513","url":null,"abstract":"Cornuside is a secoiridoid glucoside compound extracted from the fruits of Cornus officinalis. Cornuside has immunomodulatory and anti-inflammatory properties; however, its potential therapeutic effects on diabetic nephropathy (DN) have not been completely explored. In this study, we established an in vitro model of DN through treating mesangial cells (MMCs) with glucose. MMCs were then treated with different concentrations of cornuside (0, 5, 10, and 30 μM). Cell viability was determined using cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays. Levels of proinflammatory cytokines, including interleukin (IL)-6, tumor necrosis factor-α, and IL-1β were examined using enzyme-linked immunosorbent assay. Reverse transcription quantitative real-time polymerase chain reaction and Western blotting were performed to detect the expression of AKT and nuclear factor-kappa B (NF-κB)-associated genes. We found that cornuside treatment significantly reduced glucose-induced increase in MMC viability and expression of pro-inflammatory cytokines. Moreover, cornuside inhibited glucose-induced phosphorylation of AKT and NF-κB inhibitor alpha, decreased the expression of proliferating cell nuclear antigen and cyclin D1, and increased the expression of p21. Our study indicates that the anti-inflammatory properties of cornuside in DN are due to AKT and NF-κB inactivation in MMCs.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"27 6","pages":"513-520"},"PeriodicalIF":2.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10613572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54232352","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

Mad2B forms a complex with Cdc20, Cdc27, Rev3 and Rev1 in response to cisplatin-induced DNA damage. Mad2B与Cdc20、Cdc27、Rev3和Rev1形成复合物，以响应顺铂诱导的DNA损伤。

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2023-09-01 DOI: 10.4196/kjpp.2023.27.5.427

Ju Hwan Kim, Rajnikant Patel

{"title":"Mad2B forms a complex with Cdc20, Cdc27, Rev3 and Rev1 in response to cisplatin-induced DNA damage.","authors":"Ju Hwan Kim, Rajnikant Patel","doi":"10.4196/kjpp.2023.27.5.427","DOIUrl":"10.4196/kjpp.2023.27.5.427","url":null,"abstract":"Mitotic arrest deficient 2 like 2 (Mad2L2, also known as Mad2B), the human homologue of the yeast Rev7 protein, is a regulatory subunit of DNA polymerase ζ that shares high sequence homology with Mad2, the mitotic checkpoint protein. Previously, we demonstrated the involvement of Mad2B in the cisplatin-induced DNA damage response. In this study, we extend our findings to show that Mad2B is recruited to sites of DNA damage in human cancer cells in response to cisplatin treatment. We found that in undamaged cells, Mad2B exists in a complex with Polζ-Rev1 and the APC/C subunit Cdc27. Following cisplatin-induced DNA damage, we observed an increase in the recruitment of Mad2B and Cdc20 (the activators of the APC/C), to the complex. The involvement of Mad2B-Cdc20-APC/C during DNA damage has not been reported before and suggests that the APC/C is activated following cisplatin-induced DNA damage. Using an in vitro ubiquitination assay, our data confirmed Mad2B-dependent activation of APC/C in cisplatin-treated cells. Mad2B may act as an accelerator for APC/C activation during DNA damage response. Our data strongly suggest a role for Mad2B-APC/C-Cdc20 in the ubiquitination of proteins involved in the DNA damage response.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"27 5","pages":"427-436"},"PeriodicalIF":2.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d4/65/kjpp-27-5-427.PMC10466067.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10127020","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

Kinesin superfamily member 15 knockdown inhibits cell proliferation, migration, and invasion in nasopharyngeal carcinoma. Kinesin超家族成员15敲低可抑制鼻咽癌细胞的增殖、迁移和侵袭。

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2023-09-01 DOI: 10.4196/kjpp.2023.27.5.457

Yi Cai, Qianyue Lai, Xuan Zhang, Yu Zhang, Man Zhang, Shaoju Gu, Yuan Qin, Jingshen Hou, Li Zhao

{"title":"Kinesin superfamily member 15 knockdown inhibits cell proliferation, migration, and invasion in nasopharyngeal carcinoma.","authors":"Yi Cai, Qianyue Lai, Xuan Zhang, Yu Zhang, Man Zhang, Shaoju Gu, Yuan Qin, Jingshen Hou, Li Zhao","doi":"10.4196/kjpp.2023.27.5.457","DOIUrl":"10.4196/kjpp.2023.27.5.457","url":null,"abstract":"The aim of this study was to investigate the role of kinesin superfamily member 15 (KIF15) in nasopharyngeal carcinogenesis (NPC) and explore its underlying mechanisms. We employed various assays, including the CCK-8 assay, flow cytometry, the Transwell and scratch assay, Western blotting, and nude mice transplantation tumor, to investigate the impact of KIF15 on NPC. Our findings demonstrate that KIF15 plays a critical role in the proliferation, apoptosis, migration, and invasion of NPC cells. Furthermore, we discovered that silencing KIF15 inhibits cell proliferation, migration, and invasion while promoting apoptosis, and that KIF15's effect on NPC cell growth is mediated through the PI3K/AKT and P53 signaling pathways. Additionally, we showed that KIF15 promotes nasopharyngeal cancer cell growth in vivo. Our study sheds light on the significance of KIF15 in NPC by revealing that KIF15 knockdown inhibits NPC cell growth through the regulation of AKT-related signaling pathways. These findings suggest that KIF15 represents a promising therapeutic target for the prevention and treatment of NPC.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"27 5","pages":"457-470"},"PeriodicalIF":2.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/86/0f/kjpp-27-5-457.PMC10466069.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10127019","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