Korean Journal of Physiology & Pharmacology最新文献_第10页

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

Inhibition of the interaction between Hippo/YAP and Akt signaling with ursolic acid and 3'3-diindolylmethane suppresses esophageal cancer tumorigenesis. 熊果酸和 3'3-二吲哚甲烷可抑制 Hippo/YAP 和 Akt 信号之间的相互作用，从而抑制食管癌的发生。

IF 1.6 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2023-09-01 DOI: 10.4196/kjpp.2023.27.5.493

Ruo Yu Meng, Cong Shan Li, Dan Hu, Soon-Gu Kwon, Hua Jin, Ok Hee Chai, Ju-Seog Lee, Soo Mi Kim

{"title":"Inhibition of the interaction between Hippo/YAP and Akt signaling with ursolic acid and 3'3-diindolylmethane suppresses esophageal cancer tumorigenesis.","authors":"Ruo Yu Meng, Cong Shan Li, Dan Hu, Soon-Gu Kwon, Hua Jin, Ok Hee Chai, Ju-Seog Lee, Soo Mi Kim","doi":"10.4196/kjpp.2023.27.5.493","DOIUrl":"10.4196/kjpp.2023.27.5.493","url":null,"abstract":"Hippo/YAP signaling hinders cancer progression. Inactivation of this pathway contributes to the development of esophageal cancer by activation of Akt. However, the possible interaction between Akt and Hippo/YAP pathways in esophageal cancer progression is unclear. In this study, we found that ursolic acid (UA) plus 3'3-diindolylmethane (DIM) efficiently suppressed the oncogenic Akt/Gsk-3β signaling pathway while activating the Hippo tumor suppressor pathway in esophageal cancer cells. Moreover, the addition of the Akt inhibitor LY294002 and the PI3K inhibitor 3-methyladenine enhanced the inhibitory effects of UA plus DIM on Akt pathway activation and further stimulated the Hippo pathway, including the suppression of YAP nuclear translocation in esophageal cancer cells. Silencing YAP under UA plus DIM conditions significantly increased the activation of the tumor suppressor PTEN in esophageal cancer cells, while decreasing p-Akt activation, indicating that the Akt signaling pathway could be down-regulated in esophageal cancer cells by targeting PTEN. Furthermore, in a xenograft nude mice model, UA plus DIM treatment effectively diminished esophageal tumors by inactivating the Akt pathway and stimulating the Hippo signaling pathway. Thus, our study highlights a feedback loop between the PI3K/Akt and Hippo signaling pathways in esophageal cancer cells, implying that a low dose of UA plus DIM could serve as a promising chemotherapeutic combination strategy in the treatment of esophageal cancer.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"27 5","pages":"493-511"},"PeriodicalIF":1.6,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a5/cf/kjpp-27-5-493.PMC10466072.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10127017","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

Dendritic cells resist to disulfiram-induced cytotoxicity, but reduced interleukin-12/23(p40) production. 树突状细胞抵抗双硫仑诱导的细胞毒性，但减少白细胞介素-12/23(p40)的产生。

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2023-09-01 DOI: 10.4196/kjpp.2023.27.5.471

Haebeen Jung, Hong-Gu Joo

{"title":"Dendritic cells resist to disulfiram-induced cytotoxicity, but reduced interleukin-12/23(p40) production.","authors":"Haebeen Jung, Hong-Gu Joo","doi":"10.4196/kjpp.2023.27.5.471","DOIUrl":"https://doi.org/10.4196/kjpp.2023.27.5.471","url":null,"abstract":"Disulfiram (DSF), a medication for alcoholism, has recently been used as a repurposing drug owing to its anticancer effects. Despite the crucial role of dendritic cells (DCs) in immune homeostasis and cancer therapy, the effects of DSF on the survival and function of DCs have not yet been studied. Therefore, we treated bone marrow-derived DCs with DSF and lipopolysaccharide (LPS) and performed various analyses. DCs are resistant to DSF and less cytotoxic than bone marrow cells and spleen cells. The viability and metabolic activity of DCs hardly decreased after treatment with DSF in the absence or presence of LPS. DSF did not alter the expression of surface markers (MHC II, CD86, CD40, and CD54), antigen uptake capability, or the antigen-presenting ability of LPS-treated DCs. DSF decreased the production of interleukin (IL)-12/23 (p40), but not IL-6 or tumor necrosis factor-α, in LPS-treated DCs. We considered the granulocyte-macrophage colony-stimulating factor (GM-CSF) as a factor to make DCs resistant to DSF-induced cytotoxicity. The resistance of DCs to DSF decreased when GM-CSF was not given or its signaling was inhibited. Also, GM-CSF upregulated the expression of a transcription factor XBP-1 which is essential for DCs' survival. This study demonstrated for the first time that DSF did not alter the function of DCs, had low cytotoxicity, and induced differential cytokine production.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"27 5","pages":"471-479"},"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/71/67/kjpp-27-5-471.PMC10466071.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10134125","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

Peptides derived from high voltage-gated calcium channel β subunit reduce blood pressure in rats. 高压门控钙通道β亚基衍生的肽可降低大鼠血压。

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2023-09-01 DOI: 10.4196/kjpp.2023.27.5.481

Hyung Kyu Kim, Jiyeon Jun, Tae Wan Kim, Dong-Ho Youn

{"title":"Peptides derived from high voltage-gated calcium channel β subunit reduce blood pressure in rats.","authors":"Hyung Kyu Kim, Jiyeon Jun, Tae Wan Kim, Dong-Ho Youn","doi":"10.4196/kjpp.2023.27.5.481","DOIUrl":"https://doi.org/10.4196/kjpp.2023.27.5.481","url":null,"abstract":"The β subunits of high voltage-gated calcium channels (HGCCs) are essential for optimal channel functions such as channel gating, activation-inactivation kinetics, and trafficking to the membrane. In this study, we report for the first time the potent blood pressure-reducing effects of peptide fragments derived from the β subunits in anesthetized and non-anesthetized rats. Intravenous administration of 16-mer peptide fragments derived from the interacting regions of the β1 [cacb1(344-359)], β2 [cacb2(392-407)], β3 [cacb3(292-307)], and β4 [cacb4(333-348)] subunits with the main α-subunit of HGCC decreased arterial blood pressure in a dose-dependent manner for 5-8 min in anesthetized rats. In contrast, the peptides had no effect on the peak amplitudes of voltage-activated Ca2+ current upon their intracellular application into the acutely isolated trigeminal ganglion neurons. Further, a single mutated peptide of cacb1(344-359)-cacb1(344-359)K357R-showed consistent and potent effects and was crippled by a two-amino acid-truncation at the N-terminal or C-terminal end. By conjugating palmitic acid with the second amino acid (lysine) of cacb1(344-359)K357R (named K2-palm), we extended the blood pressure reduction to several hours without losing potency. This prolonged effect on the arterial blood pressure was also observed in non-anesthetized rats. On the other hand, the intrathecal administration of acetylated and amidated cacb1(344-359)K357R peptide did not change acute nociceptive responses induced by the intradermal formalin injection in the plantar surface of rat hindpaw. Overall, these findings will be useful for developing antihypertensives.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"27 5","pages":"481-491"},"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/07/8c/kjpp-27-5-481.PMC10466068.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10127018","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

Paeonol accelerates skin wound healing by regulating macrophage polarization and inflammation in diabetic rats. 丹皮酚通过调节糖尿病大鼠巨噬细胞极化和炎症加速皮肤伤口愈合。

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2023-09-01 DOI: 10.4196/kjpp.2023.27.5.437

Zuyang Zhang, Tianhua Chen, Wei Liu, Jiepeng Xiong, Liangdong Jiang, Mingjiang Liu

{"title":"Paeonol accelerates skin wound healing by regulating macrophage polarization and inflammation in diabetic rats.","authors":"Zuyang Zhang, Tianhua Chen, Wei Liu, Jiepeng Xiong, Liangdong Jiang, Mingjiang Liu","doi":"10.4196/kjpp.2023.27.5.437","DOIUrl":"https://doi.org/10.4196/kjpp.2023.27.5.437","url":null,"abstract":"Diabetic ulcer is usually seen in people with uncontrolled blood sugar. Reportedly, many factors such as impaired glucose metabolism, and macrovascular and microvascular diseases caused angiogenesis disorders and delayed the healing of diabetic ulcers, thus affecting the body's metabolism, nutrition, and immune function. This study aimed to explore the effect of paeonol on skin wound healing in diabetic rats and the related mechanism. A rat model of diabetic ulcer was established. High glucose-treated mouse skin fibroblasts were co-cultured with M1 or M2-polarized macrophages treated with or without paeonol. H&E and Masson staining were used to reveal inflammatory cell infiltration and collagen deposition, respectively. Immunohistochemistry visualized the expression of Ki67, CD31, and vascular endothelial growth factor (VEGF). Western blot was used to detect interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-4, IL-10, CD31, VEGFA, and collagen I/III. The expression of iNOS and arginase 1 was revealed by immunofluorescence staining. Paeonol treatment augmented collagen deposition and the expression of Ki67, CD31, VEGF, and macrophage M2 polarization markers (IL-4 and IL-10) and reduced wound area, inflammatory cell infiltration, and macrophage M1 polarization markers (IL-1β and TNF-α) in the ulcerated area. In vitro, paeonol treatment promoted M2-polarization and repressed M1-polarization in macrophages, thereby improving the repair of cell damage induced by high glucose. Paeonol accelerates the healing of diabetic ulcers by promoting M2 macrophage polarization and inhibiting M1 macrophage polarization.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"27 5","pages":"437-448"},"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/87/46/kjpp-27-5-437.PMC10466073.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10127025","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

N-retinylidene-N-retinylethanolamine degradation in human retinal pigment epithelial cells via memantine- and ifenprodil-mediated autophagy. 人视网膜色素上皮细胞通过美金刚和伊芬普罗地尔介导的自噬降解n -视黄醛- n -视黄醛乙醇胺。

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2023-09-01 DOI: 10.4196/kjpp.2023.27.5.449

Jae Rim Lee, Kwang Won Jeong

{"title":"N-retinylidene-N-retinylethanolamine degradation in human retinal pigment epithelial cells via memantine- and ifenprodil-mediated autophagy.","authors":"Jae Rim Lee, Kwang Won Jeong","doi":"10.4196/kjpp.2023.27.5.449","DOIUrl":"https://doi.org/10.4196/kjpp.2023.27.5.449","url":null,"abstract":"N-methyl-D-aspartate (NMDA) receptors are ionic glutamine receptors involved in brain development and functions such as learning and memory formation. NMDA receptor inhibition is associated with autophagy activation. In this study, we investigated whether the NMDA receptor antagonists, memantine and ifenprodil, induce autophagy in human retinal pigment epithelial cells (ARPE-19) to remove Nretinylidene- N-retinylethanolamine (A2E), an intracellular lipofuscin component. Fluorometric analysis using labeled A2E (A2E-BDP) and confocal microscopic examination revealed that low concentrations of NMDA receptor antagonists, which did not induce cytotoxicity, significantly reduced A2E accumulation in ARPE-19 cells. In addition, memantine and ifenprodil activated autophagy in ARPE-19 cells as measured by microtubule-associated protein 1A/1B-light chain3-II formation and phosphorylated p62 protein levels. Further, to understand the correlation between memantine- and ifenprodil-mediated A2E degradation and autophagy, autophagy-related 5 (ATG5) was depleted using RNA interference. Memantine and ifenprodil failed to degrade A2E in ARPE-19 cells lacking ATG5. Taken together, our study indicates that the NMDA receptor antagonists, memantine and ifenprodil, can remove A2E accumulated in cells via autophagy activation in ARPE-19 cells.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"27 5","pages":"449-456"},"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/a5/e4/kjpp-27-5-449.PMC10466070.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10134126","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

Shikonin ameliorates salivary gland damage and inflammation in a mouse model of Sjögren's syndrome by modulating MAPK signaling pathway. 紫草素通过调节MAPK信号通路改善Sjögren综合征小鼠唾液腺损伤和炎症。

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2023-07-01 DOI: 10.4196/kjpp.2023.27.4.357

Wenjing Guo, Xin Wang, Chao Sun, Jian Wang, Tao Wang

{"title":"Shikonin ameliorates salivary gland damage and inflammation in a mouse model of Sjögren's syndrome by modulating MAPK signaling pathway.","authors":"Wenjing Guo, Xin Wang, Chao Sun, Jian Wang, Tao Wang","doi":"10.4196/kjpp.2023.27.4.357","DOIUrl":"https://doi.org/10.4196/kjpp.2023.27.4.357","url":null,"abstract":"Sjögren syndrome (SS) is a systemic inflammatory autoimmune disease that involves exocrine glands. Shikonin is extracted from comfrey, which is conventionally used as an anti-tumor, antibacterial, and antiviral drug in China. However, the application of Shikonin in SS remains unreported. This study aimed to verify the potential functions of Shikonin in SS progression. Firstly, non-obese diabetic mice were used as the SS mouse model, with C57BL/6 mice serving as the healthy control. It was demonstrated that the salivary gland damage and inflammation were aggravated in the SS mouse model. Shikonin improved salivary gland function decline and injury in the SS mouse model. Moreover, Shikonin reduced inflammatory cytokines and immune infiltration in the SS mouse model. Further experiments discovered that Shikonin attenuated the MAPK signaling pathway in the SS mouse model. Lastly, inhibition of the MAPK signaling pathway combined with Shikonin treatment further alleviated the symptoms of SS. In conclusion, Shikonin ameliorated salivary gland damage and inflammation in a mouse model of SS by modulating the MAPK signaling pathway. Our findings indicate that Shikonin may be a useful drug for SS treatment.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"27 4","pages":"357-364"},"PeriodicalIF":2.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c2/e7/kjpp-27-4-357.PMC10316193.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9747885","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