Korean Journal of Physiology & Pharmacology最新文献

Wogonin inhibits radiation-induced DNA damage repair in hepatocellular carcinoma cells by upregulating p21.

IF 1.6 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2025-02-06 DOI: 10.4196/kjpp.24.213

Xiao Xu, Yonghong Qian, Shusheng Zhu, Hu Tian, Pingping Zhai, Shimin Zhu, Jingjing Wang, Lei Xie, Songbing Qin

{"title":"Wogonin inhibits radiation-induced DNA damage repair in hepatocellular carcinoma cells by upregulating p21.","authors":"Xiao Xu, Yonghong Qian, Shusheng Zhu, Hu Tian, Pingping Zhai, Shimin Zhu, Jingjing Wang, Lei Xie, Songbing Qin","doi":"10.4196/kjpp.24.213","DOIUrl":"https://doi.org/10.4196/kjpp.24.213","url":null,"abstract":"Wogonin has been shown to exhibit anti-tumor effects by regulating the growth and inducing cell death in hepatocellular carcinoma (HCC) cells. However, its impact on radiotherapy for HCC remains unclear. This study aimed to elucidate the mechanisms and effects of wogonin in enhancing radiotherapy for HCC. The viability and cell cycle of HCC cells were assessed using CCK-8, trypan blue dye exclusion, and flow cytometry. RNA sequencing was performed to explore the genomic effects of wogonin on HCC cells. Immunofluorescence staining was employed to detect γ-H2AX distribution, and Western blot was used to evaluate the expression of γ-H2AX and p21. Wogonin induced cell cycle arrest and inhibited DNA damage repair in SMMC-7721 and HCC-LM3 cells following irradiation. RNA sequencing analysis of wogoninand radiation-treated cells revealed significant enrichment of genes related to cell cycle progression, with notable changes in CDK inhibitor expression. Furthermore, wogonin in combination with irradiation increased the expression of γ-H2AX and p21 in HCC cells. Notably, p21 interference partially abrogated the anti-tumor effects of wogonin and radiation. Wogonin enhances the efficacy of radiotherapy in HCC by promoting cell cycle arrest and inhibiting DNA damage repair through upregulation of p21.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cholestyramine in hemodialysis: a new approach for hyperphosphatemia management.

IF 1.6 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2025-02-06 DOI: 10.4196/kjpp.24.269

Ahmed Essam Abd El Hady Ali Ghanem, Radwa Maher El Borolossy, Tamer Wahid El Said, Sara Mahmoud Zaki Shaheen

{"title":"Cholestyramine in hemodialysis: a new approach for hyperphosphatemia management.","authors":"Ahmed Essam Abd El Hady Ali Ghanem, Radwa Maher El Borolossy, Tamer Wahid El Said, Sara Mahmoud Zaki Shaheen","doi":"10.4196/kjpp.24.269","DOIUrl":"https://doi.org/10.4196/kjpp.24.269","url":null,"abstract":"Hyperphosphatemia is a potentially life altering condition in end-stage renal disease patients who are on regular hemodialysis that can lead to cardiovascular calcification, metabolic bone disease and secondary hyperparathyroidism. Bile acid sequestrants are anion exchange resins bind to bile acids and phosphate in the intestine resulting in preventing intestinal absorption of dietary phosphate, interruption of bile acid homeostasis and reduction in low-density lipoprotein cholesterol levels. Cholestyramine is chosen for study in hemodialysis patients based on the effectiveness and safety of bile acid sequestrants such colestilan and colestipol in the treatment of hyperphosphatemia and hypercholesterolemia in hemodialysis patients. A prospective, interventional, randomized, double blinded, placebo-controlled two arm study was carried out to assess the efficacy of oral cholestyramine on reduction of serum phosphate level in adult hemodialysis patients. 76 eligible patients were randomly assigned to either a drug group or a placebo group for the 2-month study period. The protocol was approved by the institutional review board of the faculty of pharmacy Ain Shams University Ethical committee and has been registered on ClinicalTrials.gov: NCT05577507. Over the 2-month treatment period, patients in cholestyramine group showed a significant decline in serum phosphorus levels versus placebo group (4.6 mg/dl vs. 6.6 mg/dl; p < 0.001) and serum calcium-phosphorus product (40 mg2/dl2 vs. 59.8 mg2/dl2; p < 0.001). Median serum triglyceride and low-density lipoprotein cholesterol levels had decreased significantly versus baseline values in the cholestyramine group. Cholestyramine used with phosphate binders effectively lowers phosphorus levels, improves the lipid profile, and has mild adverse effects.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"128"},"PeriodicalIF":1.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neurosteroids and neurological disorders. 神经类固醇和神经紊乱。

IF 1.6 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2025-01-14 DOI: 10.4196/kjpp.24.353

Gi Wan Park, Hayoung Kim, Seong Hyun Won, Nam Hyun Kim, Sheu-Ran Choi

引用次数: 0

Microglial galectin-3 increases with aging in the mouse hippocampus. 小鼠海马小胶质半凝集素-3随着年龄的增长而增加。

IF 1.6 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2025-01-14 DOI: 10.4196/kjpp.24.196

Hyun Joo Shin, So Jeong Lee, Hyeong Seok An, Ha Nyeoung Choi, Eun Ae Jeong, Jaewoong Lee, Kyung Eun Kim, Bong-Hoi Choi, Seung Pil Yun, Dawon Kang, Sang Soo Kang, Gu Seob Roh

{"title":"Microglial galectin-3 increases with aging in the mouse hippocampus.","authors":"Hyun Joo Shin, So Jeong Lee, Hyeong Seok An, Ha Nyeoung Choi, Eun Ae Jeong, Jaewoong Lee, Kyung Eun Kim, Bong-Hoi Choi, Seung Pil Yun, Dawon Kang, Sang Soo Kang, Gu Seob Roh","doi":"10.4196/kjpp.24.196","DOIUrl":"https://doi.org/10.4196/kjpp.24.196","url":null,"abstract":"Microglial activation during aging is associated with neuroinflammation and cognitive impairment. Galectin-3 plays a crucial role in microglial activation and phagocytosis. However, the role of galectin-3 in the aged brain is not completely understood. In the present study, we investigated aging-related mechanisms and microglial galectin-3 expression in the mouse hippocampus using female 6-, 12-, and 24-month-old C57BL/6 mice. Western blot analysis revealed neurodegeneration, blood-brain barrier leakage, and increased levels of neuroinflammation-related proteins in 24-month-old mice compared to 6- and 12-month-old mice. Immunohistochemistry revealed an increase in activated microglia in the hippocampus of 24-month-old mice compared to 6- and 12-month-old mice. Furthermore, we found more galectin-3 and triggering receptor expressed on myeloid cells-2-positive microglia in 24-month-old mice compared to 6- and 12-month-old mice. Using primary mouse microglial cells, galectin -3 was also increased by lipopolysaccharide treatment. These findings suggest that galectin-3 may play an important role in microglial activation and neuroinflammation during brain aging.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Melittin inhibits MPP⁺-induced HT22 cell death by suppressing Bax activation and improving mitochondrial function. 蜂毒素通过抑制Bax激活和改善线粒体功能抑制MPP+诱导的HT22细胞死亡。

IF 1.6 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2025-01-06 DOI: 10.4196/kjpp.24.293

Tingting Yu, Zirui Yuan, Jiaona Yu, Lu Chen, Wei Hao, Xiaohui Xu

{"title":"Melittin inhibits MPP+-induced HT22 cell death by suppressing Bax activation and improving mitochondrial function.","authors":"Tingting Yu, Zirui Yuan, Jiaona Yu, Lu Chen, Wei Hao, Xiaohui Xu","doi":"10.4196/kjpp.24.293","DOIUrl":"https://doi.org/10.4196/kjpp.24.293","url":null,"abstract":"Melittin (MEL) is the main bioactive component of bee venom and has been reported to have various pharmacological effects. This study investigates the protective effect of MEL on MPP+-injured HT22 cells and the possible mechanisms involved. We treated the cells with 4 mM MPP+ for 24 h to induce a cellular injury model. HT22 cells were pretreated with 0.1 μM MEL for 6 h and then exposed to 4 mM MPP+ for 24 h. We measured cell viability, the expression of Bax, the indicators and protein levels associated with apoptosis and parthanatos, and the co-localisation of MEL and mitochondria, and mitochondrial function-related indices such as the mitochondrial membrane potential (MMP) and mito-SOX. We show that PAR protein expression was significantly increased in the MPP+-treated cell model and that the parthanatos inhibitor DPQ significantly reduced MPP+-induced cell death, suggesting that MPP+ can cause PARP1-dependent cell death. MEL significantly inhibited cell death, increased cell viability as well as NAD+ and ATP levels, increased the expression of Bcl-2 and suppressed the activation of Bax, cleaved-caspase3, and cleaved- PARP1. Moreover, MEL was found to be localised on the mitochondria of HT22 cells and to improve mitochondrial functions including increased MMP and decreased mitochondrial reactive oxygen species. We speculate that MEL may protect neurons against MPP+-induced HT22 cell injury by inhibiting Bax activation, suppressing changes in mitochondrial permeability, and improving mitochondrial function, thereby preventing cell parthanatos and apoptosis.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Differential expression of ORAI channels and STIM proteins in renal cell carcinoma subtypes: implications for metastasis and therapeutic targeting. 肾细胞癌亚型中 ORAI 通道和 STIM 蛋白的差异表达：对转移和靶向治疗的影响。

IF 1.6 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2025-01-01 Epub Date: 2024-10-31 DOI: 10.4196/kjpp.24.126

Ji-Hee Kim, Kyu-Hee Hwang, Jiyeon Oh, Sung-Eun Kim, Mi-Young Lee, Tae Sic Lee, Seung-Kuy Cha

{"title":"Differential expression of ORAI channels and STIM proteins in renal cell carcinoma subtypes: implications for metastasis and therapeutic targeting.","authors":"Ji-Hee Kim, Kyu-Hee Hwang, Jiyeon Oh, Sung-Eun Kim, Mi-Young Lee, Tae Sic Lee, Seung-Kuy Cha","doi":"10.4196/kjpp.24.126","DOIUrl":"10.4196/kjpp.24.126","url":null,"abstract":"Renal cell carcinoma (RCC) presents significant clinical challenges, highlighting the importance of understanding its molecular mechanisms. While store-operated Ca2+ entry (SOCE) is known to play an essential role in tumorigenesis and metastasis, its specific implications across various RCC subtypes remain underexplored. This study analyzed SOCE-related mRNA profiles from the KIRC and KIRP projects in The Cancer Genome Atlas (TCGA) database, focusing on differential gene expression and overall survival outcomes. Functional studies in clear cell RCC (Caki-1) and papillary RCC cell lines (pRCC, Caki-2) revealed increased expression of Orai1 and Orai3, along with STIM1, exhibited in both subtypes, with decreased STIM2 and increased Orai2 expression in pRCC. Notably, Orai3 expression had a gender-specific impact on survival, particularly in females with pRCC, where it inversely correlated with STIM2 expression. Functional assays showed Orai3 dominance in Caki-2 and Orai1 in Caki- 1. Interestingly, 2-APB inhibited SOCE in Caki-1 but enhanced it in Caki-2, suggesting Orai3 as the primary SOCE channel in pRCC. Knockdown of Orai1 and Orai3 reduced cell migration and proliferation via regulating focal adhesion kinase (FAK) and Cyclin D1 in both cell lines. These findings highlight the critical roles of Orai1 and Orai3 in RCC metastasis, with Orai3 linked to poorer prognosis in females with pRCC. This study offers valuable insights into RCC diagnostics and potential therapeutic strategies targeting ORAI channels and STIM proteins.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"33-43"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559472","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

Fine particulate matter induces osteoclast-mediated bone loss in mice. 细颗粒物会诱发小鼠破骨细胞介导的骨质流失。

IF 1.6 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2025-01-01 Epub Date: 2024-10-31 DOI: 10.4196/kjpp.24.115

Hye Young Mun, Septika Prismasari, Jeong Hee Hong, Hana Lee, Doyong Kim, Han Sung Kim, Dong Min Shin, Jung Yun Kang

{"title":"Fine particulate matter induces osteoclast-mediated bone loss in mice.","authors":"Hye Young Mun, Septika Prismasari, Jeong Hee Hong, Hana Lee, Doyong Kim, Han Sung Kim, Dong Min Shin, Jung Yun Kang","doi":"10.4196/kjpp.24.115","DOIUrl":"10.4196/kjpp.24.115","url":null,"abstract":"Fine particulate matter (FPM) is a major component of air pollution and has emerged as a significant global health concern owing to its adverse health effects. Previous studies have investigated the correlation between bone health and FPM through cohort or review studies. However, the effects of FPM exposure on bone health are poorly understood. This study aimed to investigate the effects of FPM on bone health and elucidate these effects in vitro and in vivo using mice. Micro-CT analysis in vivo revealed FPM exposure decreased bone mineral density, trabecular bone volume/total volume ratio, and trabecular number in the femurs of mice, while increasing trabecular separation. Histological analysis showed that the FPM-treated group had a reduced trabecular area and an increased number of osteoclasts in the bone tissue. Moreover, in vitro studies revealed that low concentrations of FPM significantly enhanced osteoclast differentiation. These findings further support the notion that short-term FPM exposure negatively impacts bone health, providing a foundation for further research on this topic.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"9-19"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559473","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

Astragalus polysaccharide ameliorates diabetic retinopathy by inhibiting the SHH-Gli1-AQP1 signaling pathway in streptozotocin-induced type 2 diabetic rats. 黄芪多糖通过抑制链脲佐菌素诱导的2型糖尿病大鼠的SHH-Gli1-AQP1信号通路改善糖尿病视网膜病变

IF 1.6 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2025-01-01 Epub Date: 2024-11-14 DOI: 10.4196/kjpp.23.251

Jingrong Qu, Bo Wang, Yulong Wang, Hao Li, Xiaomei An

{"title":"Astragalus polysaccharide ameliorates diabetic retinopathy by inhibiting the SHH-Gli1-AQP1 signaling pathway in streptozotocin-induced type 2 diabetic rats.","authors":"Jingrong Qu, Bo Wang, Yulong Wang, Hao Li, Xiaomei An","doi":"10.4196/kjpp.23.251","DOIUrl":"10.4196/kjpp.23.251","url":null,"abstract":"This study aims to investigate the effects of astragalus polysaccharide (APS) on diabetic retinopathy through the SHH-Gli1-AQP1 pathway. The anti-type 2 diabetes mellitus (T2DM) targets of APS were identified through comprehensive searches of drug and disease-related databases. A protein-protein interaction network was then constructed, followed by GO and KEGG enrichment analyses. Molecular docking simulations were performed to evaluate the interactions of APS and metformin with Gli1 and AQP1. An in vivo T2DM rat model was established via streptozotocin (STZ) injection and treated with metformin and varying doses of APS for 12 weeks. Histological changes in retinal cells were assessed using H&E and PAS staining. The expression levels of AQP1, Gli1, and SHH in the retina were measured using immunohistochemistry, Western blotting, immunofluorescence, and ELISA. Additionally, mRNA expression of AQP1, Gli1, and SHH was quantified by RT-qPCR. Bioinformatic analyses indicated that Gli1 and AQP1, key components of the SHH-Gli1- AQP1 signaling pathway, may be associated with T2DM. Subsequent experiments demonstrated that the STZ-induced T2DM rats exhibited significant retinal damage, which was notably mitigated by both APS and metformin treatments. Furthermore, the SHH-Gli1-AQP1 signaling pathway was found to be overactivated in STZ-induced T2DM rats. Treatment with APS and metformin significantly reduced the elevated expression levels of SHH, Gli1, and AQP1. APS effectively inhibits retinal damage of STZ-induced T2DM rats by restraining the SHH-Gli1-AQP1 signaling pathway.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"21-32"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632817","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

Mebendazole effectively overcomes imatinib resistance by dual-targeting BCR/ABL oncoprotein and β-tubulin in chronic myeloid leukemia cells. 甲苯达唑通过双重靶向慢性骨髓性白血病细胞中的BCR/ABL癌蛋白和β-微管蛋白，有效克服伊马替尼耐药性。

IF 1.6 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2025-01-01 Epub Date: 2024-11-14 DOI: 10.4196/kjpp.24.176

Li Yang, Zhuanyun Du, Yuhang Peng, Wenyao Zhang, Wenli Feng, Ying Yuan

{"title":"Mebendazole effectively overcomes imatinib resistance by dual-targeting BCR/ABL oncoprotein and β-tubulin in chronic myeloid leukemia cells.","authors":"Li Yang, Zhuanyun Du, Yuhang Peng, Wenyao Zhang, Wenli Feng, Ying Yuan","doi":"10.4196/kjpp.24.176","DOIUrl":"10.4196/kjpp.24.176","url":null,"abstract":"To target the pivotal BCR/ABL oncoprotein in chronic myeloid leukemia (CML) cells, tyrosine kinase inhibitors (TKIs) are utilized as landmark achievements in CML therapy. However, TKI resistance and intolerance remain principal obstacles in the treatment of CML patients. In recent years, drug repositioning provided alternative and promising perspectives apart from the classical cancer therapies, and promoted anthelmintic mebendazole (MBZ) as an effective anti-cancer drug in various cancers. Here, we investigated the role of MBZ in CML treatment including imatinib-resistant CML cells. Our results proved that MBZ inhibited the proliferation and induced apoptosis in CML cells. We found that MBZ effectively suppressed BCR/ABL kinase activity and MEK/ERK signaling pathway by reducing p-BCR/ABL and p-ERK levels with ABL1 targeting ability. Meanwhile, MBZ directly targeted the colchicine-binding site of β-tubulin protein, hampered microtubule polymerization and induced mitosis arrest and mitotic catastrophe. In addition, MBZ increased DNA damage levels and hampered the accumulation of ataxia-telangiectasia mutated and DNA-dependent protein kinase into the nucleus. This work discovered that anthelmintic MBZ exerts remarkable anticancer effects in both imatinib-sensitive and imatinib-resistant CML cells in vitro and revealed mechanisms underlying. From the perspective of drug repositioning and multi-target therapeutic strategy, this study provides a promising option for CML treatment, especially in TKI-resistant or intolerant individuals.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"67-81"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632823","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

p66shc deficiency attenuates high glucose-induced autophagy dysfunction in Schwann cells. p66shc 缺乏症可减轻高糖诱导的许旺细胞自噬功能障碍。

IF 1.6 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2025-01-01 Epub Date: 2024-10-31 DOI: 10.4196/kjpp.24.155

Su-Jeong Choi, Giang-Huong Vu, Harsha Nagar, Seonhee Kim, Ikjun Lee, Shuyu Piao, Byeong Hwa Jeon, Kaikobad Irani, Sang-Ha Oh, Cuk-Seong Kim

{"title":"p66shc deficiency attenuates high glucose-induced autophagy dysfunction in Schwann cells.","authors":"Su-Jeong Choi, Giang-Huong Vu, Harsha Nagar, Seonhee Kim, Ikjun Lee, Shuyu Piao, Byeong Hwa Jeon, Kaikobad Irani, Sang-Ha Oh, Cuk-Seong Kim","doi":"10.4196/kjpp.24.155","DOIUrl":"10.4196/kjpp.24.155","url":null,"abstract":"Schwann cells are the most abundant cells in the peripheral nervous system, maintaining the development, function and regeneration of peripheral nerves. Defects in these Schwann cells injury response potentially contribute to the pathogenesis of diabetic peripheral neuropathy (DPN), a common complication of diabetes mellitus. The protein p66shc is essential in regulating oxidative stress responses, autophagy induction and cell survival, and is also vital in the development of DPN. In this study, we hypothesized that p66shc mediates high glucose-induced oxidative stress and autophagic dysfunction. In Schwann cells treated with high glucose; p66shc expression, levels of reactive oxygen species, autophagy impairment, and early apoptosis were elevated. Inhibition of p66shc gene expression by siRNA reversed high glucose-induced oxidative stress, autophagy impairment, and early apoptosis. We also demonstrated that the levels of p66shc was increased, while autophagy-related proteins p62 and LC3 (LC3-II/I) were suppressed in the sciatic nerve of streptozotocin-induced diabetes mice. P66shc-deficient mice exhibited the improvement in autophagy impairment after diabetes onset. Our findings suggest that the p66 plays a crucial role in Schwann cell dysfunction, identifying its potential as a therapeutic target.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"57-66"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559475","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