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The interactive effects of different exercises and hawthorn consumption on the pain threshold of TMT-induced Alzheimer male rats. 不同运动和食用山楂对TMT诱导的阿尔茨海默症雄性大鼠痛阈的交互影响
IF 2.6 4区 医学
Journal of Physiological Sciences Pub Date : 2024-07-16 DOI: 10.1186/s12576-024-00925-4
Ensiyeh Almasi, Ali Heidarianpour, Maryam Keshvari
{"title":"The interactive effects of different exercises and hawthorn consumption on the pain threshold of TMT-induced Alzheimer male rats.","authors":"Ensiyeh Almasi, Ali Heidarianpour, Maryam Keshvari","doi":"10.1186/s12576-024-00925-4","DOIUrl":"10.1186/s12576-024-00925-4","url":null,"abstract":"<p><p>Exercise increases the pain threshold in healthy people. However, the pain threshold modulation effect of exercise and hawthorn is unclear because of its potential benefits in people with persistent pain, including those with Alzheimer's disease. Accordingly, after the induction of Alzheimer's disease by trimethyl chloride, male rats with Alzheimer's disease were subjected to a 12-week training regimen consisting of resistance training, swimming endurance exercises, and combined exercises. In addition, hawthorn extract was orally administered to the rats. Then, their pain threshold was evaluated using three Tail-flick, Hot-plate, and Formalin tests. Our results showed that Alzheimer's decreased the pain threshold in all three behavioral tests. Combined exercise with hawthorn consumption had the most statistically significant effect on Alzheimer's male rats' pain threshold in all three experiments. A combination of swimming endurance and resistance exercises with hawthorn consumption may modulate hyperalgesia in Alzheimer's rats. Future studies need to determine the effects of these factors on the treatment and/or management of painful conditions.</p>","PeriodicalId":16832,"journal":{"name":"Journal of Physiological Sciences","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11251243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626956","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
Cytotoxic effects of the cigarette smoke extract of heated tobacco products on human oral squamous cell carcinoma: the role of reactive oxygen species and CaMKK2. 加热烟草制品的烟气提取物对人类口腔鳞状细胞癌的细胞毒性作用:活性氧和 CaMKK2 的作用。
IF 2.6 4区 医学
Journal of Physiological Sciences Pub Date : 2024-06-25 DOI: 10.1186/s12576-024-00928-1
Nagao Kagemichi, Masanari Umemura, Soichiro Ishikawa, Yu Iida, Shota Takayasu, Akane Nagasako, Rina Nakakaji, Taisuke Akimoto, Makoto Ohtake, Takahiro Horinouchi, Tetsuya Yamamoto, Yoshihiro Ishikawa
{"title":"Cytotoxic effects of the cigarette smoke extract of heated tobacco products on human oral squamous cell carcinoma: the role of reactive oxygen species and CaMKK2.","authors":"Nagao Kagemichi, Masanari Umemura, Soichiro Ishikawa, Yu Iida, Shota Takayasu, Akane Nagasako, Rina Nakakaji, Taisuke Akimoto, Makoto Ohtake, Takahiro Horinouchi, Tetsuya Yamamoto, Yoshihiro Ishikawa","doi":"10.1186/s12576-024-00928-1","DOIUrl":"10.1186/s12576-024-00928-1","url":null,"abstract":"<p><strong>Background: </strong>The increasing prevalence of heated tobacco products (HTPs) has heightened concerns regarding their potential health risks. Previous studies have demonstrated the toxicity of cigarette smoke extract (CSE) from traditional tobacco's mainstream smoke, even after the removal of nicotine and tar. Our study aimed to investigate the cytotoxicity of CSE derived from HTPs and traditional tobacco, with a particular focus on the role of reactive oxygen species (ROS) and intracellular Ca<sup>2+</sup>.</p><p><strong>Methods: </strong>A human oral squamous cell carcinoma (OSCC) cell line, HSC-3 was utilized. To prepare CSE, aerosols from HTPs (IQOS) and traditional tobacco products (1R6F reference cigarette) were collected into cell culture media. A cell viability assay, apoptosis assay, western blotting, and Fluo-4 assay were conducted. Changes in ROS levels were measured using electron spin resonance spectroscopy and the high-sensitivity 2',7'-dichlorofluorescein diacetate assay. We performed a knockdown of calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) by shRNA lentivirus in OSCC cells.</p><p><strong>Results: </strong>CSE from both HTPs and traditional tobacco exhibited cytotoxic effects in OSCC cells. Exposure to CSE from both sources led to an increase in intracellular Ca<sup>2+</sup> concentration and induced p38 phosphorylation. Additionally, these extracts prompted cell apoptosis and heightened ROS levels. N-acetylcysteine (NAC) mitigated the cytotoxic effects and p38 phosphorylation. Furthermore, the knockdown of CaMKK2 in HSC-3 cells reduced cytotoxicity, ROS production, and p38 phosphorylation in response to CSE.</p><p><strong>Conclusion: </strong>Our findings suggest that the CSE from both HTPs and traditional tobacco induce cytotoxicity. This toxicity is mediated by ROS, which are regulated through Ca<sup>2+</sup> signaling and CaMKK2 pathways.</p>","PeriodicalId":16832,"journal":{"name":"Journal of Physiological Sciences","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11197199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450741","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
Physiology of the volume-sensitive/regulatory anion channel VSOR/VRAC: part 2: its activation mechanisms and essential roles in organic signal release. 体积敏感/调节阴离子通道 VSOR/VRAC 的生理学:第 2 部分:其激活机制和在有机信号释放中的重要作用。
IF 2.3 4区 医学
Journal of Physiological Sciences Pub Date : 2024-06-14 DOI: 10.1186/s12576-024-00926-3
Yasunobu Okada
{"title":"Physiology of the volume-sensitive/regulatory anion channel VSOR/VRAC: part 2: its activation mechanisms and essential roles in organic signal release.","authors":"Yasunobu Okada","doi":"10.1186/s12576-024-00926-3","DOIUrl":"10.1186/s12576-024-00926-3","url":null,"abstract":"<p><p>The volume-sensitive outwardly rectifying or volume-regulated anion channel, VSOR/VRAC, which was discovered in 1988, is expressed in most vertebrate cell types, and is essentially involved in cell volume regulation after swelling and in the induction of cell death. This series of review articles describes what is already known and what remains to be uncovered about the functional and molecular properties as well as the physiological and pathophysiological roles of VSOR/VRAC. This Part 2 review article describes, from the physiological and pathophysiological standpoints, first the pivotal roles of VSOR/VRAC in the release of autocrine/paracrine organic signal molecules, such as glutamate, ATP, glutathione, cGAMP, and itaconate, as well as second the swelling-independent and -dependent activation mechanisms of VSOR/VRAC. Since the pore size of VSOR/VRAC has now well been evaluated by electrophysiological and 3D-structural methods, the signal-releasing activity of VSOR/VRAC is here discussed by comparing the molecular sizes of these organic signals to the channel pore size. Swelling-independent activation mechanisms include a physicochemical one caused by the reduction of intracellular ionic strength and a biochemical one caused by oxidation due to stimulation by receptor agonists or apoptosis inducers. Because some organic substances released via VSOR/VRAC upon cell swelling can trigger or augment VSOR/VRAC activation in an autocrine fashion, swelling-dependent activation mechanisms are to be divided into two phases: the first phase induced by cell swelling per se and the second phase caused by receptor stimulation by released organic signals.</p>","PeriodicalId":16832,"journal":{"name":"Journal of Physiological Sciences","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11177392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320984","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
Identification of hypothermia-inducing neurons in the preoptic area and activation of them by isoflurane anesthesia and central injection of adenosine. 鉴定视前区的低体温诱导神经元,并通过异氟醚麻醉和中枢注射腺苷激活它们。
IF 2.3 4区 医学
Journal of Physiological Sciences Pub Date : 2024-06-12 DOI: 10.1186/s12576-024-00927-2
Erika Uchino, Ikue Kusumoto-Yoshida, Hideki Kashiwadani, Yuichi Kanmura, Akira Matsunaga, Tomoyuki Kuwaki
{"title":"Identification of hypothermia-inducing neurons in the preoptic area and activation of them by isoflurane anesthesia and central injection of adenosine.","authors":"Erika Uchino, Ikue Kusumoto-Yoshida, Hideki Kashiwadani, Yuichi Kanmura, Akira Matsunaga, Tomoyuki Kuwaki","doi":"10.1186/s12576-024-00927-2","DOIUrl":"10.1186/s12576-024-00927-2","url":null,"abstract":"<p><p>Hibernation and torpor are not passive responses caused by external temperature drops and fasting but are active brain functions that lower body temperature. A population of neurons in the preoptic area was recently identified as such active torpor-regulating neurons. We hypothesized that the other hypothermia-inducing maneuvers would also activate these neurons. To test our hypothesis, we first refined the previous observations, examined the brain regions explicitly activated during the falling phase of body temperature using c-Fos expression, and confirmed the preoptic area. Next, we observed long-lasting hypothermia by reactivating torpor-tagged Gq-expressing neurons using the activity tagging and DREADD systems. Finally, we found that about 40-60% of torpor-tagged neurons were activated by succeeding isoflurane anesthesia and by icv administration of an adenosine A1 agonist. Isoflurane-induced and central adenosine-induced hypothermia is, at least in part, an active process mediated by the torpor-regulating neurons in the preoptic area.</p>","PeriodicalId":16832,"journal":{"name":"Journal of Physiological Sciences","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11167735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310860","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
Effects of endurance training under calorie restriction on energy substrate metabolism in mouse skeletal muscle and liver. 卡路里限制下的耐力训练对小鼠骨骼肌和肝脏能量底物代谢的影响
IF 2.3 4区 医学
Journal of Physiological Sciences Pub Date : 2024-06-07 DOI: 10.1186/s12576-024-00924-5
Kenya Takahashi, Yu Kitaoka, Hideo Hatta
{"title":"Effects of endurance training under calorie restriction on energy substrate metabolism in mouse skeletal muscle and liver.","authors":"Kenya Takahashi, Yu Kitaoka, Hideo Hatta","doi":"10.1186/s12576-024-00924-5","DOIUrl":"10.1186/s12576-024-00924-5","url":null,"abstract":"<p><p>We investigated whether calorie restriction (CR) enhances metabolic adaptations to endurance training (ET). Ten-week-old male Institute of Cancer Research (ICR) mice were fed ad libitum or subjected to 30% CR. The mice were subdivided into sedentary and ET groups. The ET group performed treadmill running (20-25 m/min, 30 min, 5 days/week) for 5 weeks. We found that CR decreased glycolytic enzyme activity and monocarboxylate transporter (MCT) 4 protein content, while enhancing glucose transporter 4 protein content in the plantaris and soleus muscles. Although ET and CR individually increased citrate synthase activity in the plantaris muscle, the ET-induced increase in respiratory chain complex I protein content was counteracted by CR. In the soleus muscle, mitochondrial enzyme activity and protein levels were increased by ET, but decreased by CR. It has been suggested that CR partially interferes with skeletal muscle adaptation to ET.</p>","PeriodicalId":16832,"journal":{"name":"Journal of Physiological Sciences","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11157813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288250","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
From bench to bedside: US-Japan Collaborative Workshop on the NVU. 从工作台到床边:美国和日本关于无核化单元的合作研讨会。
IF 2.3 4区 医学
Journal of Physiological Sciences Pub Date : 2024-05-30 DOI: 10.1186/s12576-024-00917-4
{"title":"From bench to bedside: US-Japan Collaborative Workshop on the NVU.","authors":"","doi":"10.1186/s12576-024-00917-4","DOIUrl":"10.1186/s12576-024-00917-4","url":null,"abstract":"<p><p>The joint workshop between U.S. and Japanese researchers, supported by The U.S.-Japan Brain Research Cooperative Program, convened in January 2023 at Keio University Mita campus in Tokyo, Japan. The workshop had a threefold objective. Firstly, it aimed to facilitate robust exchanges between U.S. and Japanese researchers engaged in Neurovascular Unit (NVU) research, enhancing the global network of scholars in the field. Secondly, it aimed to encourage the initiation of collaborative research projects, fostering interdisciplinary efforts and synergistic advancements in understanding the brain vascular physiology and central nervous system. Lastly, the workshop emphasized the nurturing of young researchers, recognizing their pivotal role in shaping the future of NVU research. Throughout the workshop, participants discussed fundamental aspects of the NVU, exploring its complex connections and vital functions. By sharing their expertise and insights, the workshop attendees sought to uncover novel approaches to mitigate the burden of neurological diseases for individuals worldwide. This report provides a summary of the presentations and discussions held during the workshop, showcasing the collective efforts and progress made by the participants.</p>","PeriodicalId":16832,"journal":{"name":"Journal of Physiological Sciences","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11137876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141180136","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
Wireless system for recording evoked potentials. 用于记录诱发电位的无线系统
IF 2.3 4区 医学
Journal of Physiological Sciences Pub Date : 2024-05-21 DOI: 10.1186/s12576-024-00923-6
Yutaro Oguma, Toshi Nakajima, Megan Elizabeth Young, Ryoi Tamura
{"title":"Wireless system for recording evoked potentials.","authors":"Yutaro Oguma, Toshi Nakajima, Megan Elizabeth Young, Ryoi Tamura","doi":"10.1186/s12576-024-00923-6","DOIUrl":"10.1186/s12576-024-00923-6","url":null,"abstract":"<p><p>Experiments measuring evoked potentials require flexible and rapid adjustment of stimulation and recording parameters. In this study, we have developed a recording system and an associated Android application that allow making such adjustments wirelessly. The system consists of 3 units: for stimulation, recording and control. Most of the modules in this system are custom made, although the stimulator and tablet are off-the-shelf products. When installed on the tablet, our Android application allows wireless communication with the control unit from a distance of 5 m. In testing, the recording unit had low internal noise and displayed signals faithfully. Upon receiving commands from the control unit, the stimulation unit produced precisely timed pulse outputs. Using this system, we were able to record evoked field potentials in the dentate gyrus of a rat; responses increased as expected with increasing stimulation pulse amplitude and duration.</p>","PeriodicalId":16832,"journal":{"name":"Journal of Physiological Sciences","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11106879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076109","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 evidence to date: implications of l-ascorbic acid in the pathophysiology of aging. 迄今为止的证据:抗坏血酸对衰老病理生理学的影响。
IF 2.6 4区 医学
Journal of Physiological Sciences Pub Date : 2024-05-11 DOI: 10.1186/s12576-024-00922-7
Ayami Sato, Yoshitaka Kondo, Akihito Ishigami
{"title":"The evidence to date: implications of l-ascorbic acid in the pathophysiology of aging.","authors":"Ayami Sato, Yoshitaka Kondo, Akihito Ishigami","doi":"10.1186/s12576-024-00922-7","DOIUrl":"10.1186/s12576-024-00922-7","url":null,"abstract":"<p><p>L-Ascorbic acid, commonly known as vitamin C, has been used not only for disease prevention and in complementary and alternative medicine, but also for anti-aging purposes. However, the scientific evidence is not yet sufficient. Here, we review the physiological functions of vitamin C and its relationship with various pathological conditions, including our previous findings, and discuss the prospects of its application in healthy longevity. In summary, vitamin C levels are associated with lifespan in several animal models. Furthermore, clinical studies have shown that the blood vitamin C levels are lower in middle-aged and older adults than in younger adults. Lower blood vitamin C levels have also been observed in various pathological conditions such as chronic kidney disease and chronic obstructive pulmonary disease in the elderly. These observations suggest the implications of vitamin C in age-related pathological mechanisms owing to its physiological functions.</p>","PeriodicalId":16832,"journal":{"name":"Journal of Physiological Sciences","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11088021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140904419","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
Acetate ameliorates ovarian mitochondrial dysfunction in letrozole-induced polycystic ovarian syndrome rat model by improving mitofusin-2. 醋酸酯通过改善丝裂霉素-2,改善来曲唑诱导的多囊卵巢综合征大鼠模型的卵巢线粒体功能障碍。
IF 2.3 4区 医学
Journal of Physiological Sciences Pub Date : 2024-04-01 DOI: 10.1186/s12576-024-00908-5
Kehinde S Olaniyi, Stephanie E Areloegbe
{"title":"Acetate ameliorates ovarian mitochondrial dysfunction in letrozole-induced polycystic ovarian syndrome rat model by improving mitofusin-2.","authors":"Kehinde S Olaniyi, Stephanie E Areloegbe","doi":"10.1186/s12576-024-00908-5","DOIUrl":"10.1186/s12576-024-00908-5","url":null,"abstract":"<p><p>Androgen excess and metabolic abnormality largely contribute to the pathogenesis of polycystic ovarian syndrome (PCOS), which primarily precipitates ovarian dysfunction and infertility in reproductive-age women. Impaired mitochondrial function and epigenetic alteration have been linked to the development of PCOS. However, it is unknown whether acetate would exert a therapeutic effect on ovarian mitochondrial dysfunction in PCOS. Herein, the study hypothesized that acetate reverses ovarian mitochondrial dysfunction in experimental PCOS rat model, possibly through modulation of mitofusin-2 (MFn2). Eight-week-old female Wistar rats were randomized into four groups (n = 5). Induction of PCOS was performed by 1 mg/kg letrozole (p.o.), administered for 21 days. Thereafter, the rats were treated with acetate (200 mg/kg; p.o.) for 6 weeks. The PCOS rats demonstrated androgen excess, multiple ovarian cysts, elevated anti-mullerian hormone and leptin and decreased SHBG, adiponectin and 17-β estradiol with corresponding increase in ovarian transforming growth factor-β1. Additionally, inflammation (tumor growth factor and nuclear factor-kB), elevated caspase-6, decreased hypoxia-inducible factor-1α and elevated histone deacetylase-2 (HDAC2) were observed in the ovaries of PCOS rats, while mitochondrial abnormality with evidence of decreased adenosine triphosphate synthase and MFn2 was observed in rats with PCOS. Treatment with acetate reversed the alterations. The present results collectively suggest that acetate ameliorates ovarian mitochondrial abnormality, a beneficial effect that is accompanied by MFn2 with consequent normalization of reproductive-endocrine profile and ovarian function. Perhaps, the present data provide hope for PCOS individuals that suffer infertility.</p>","PeriodicalId":16832,"journal":{"name":"Journal of Physiological Sciences","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10983676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140336084","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
Negative regulation of thyroid adenoma-associated protein (THADA) in the cardiac glycoside-induced anti-cancer effect. 甲状腺腺瘤相关蛋白(THADA)在强心甙诱导的抗癌效应中的负调控作用
IF 2.3 4区 医学
Journal of Physiological Sciences Pub Date : 2024-04-01 DOI: 10.1186/s12576-024-00914-7
Mizuki Katoh, Takuto Fujii, Yoshiaki Tabuchi, Takahiro Shimizu, Hideki Sakai
{"title":"Negative regulation of thyroid adenoma-associated protein (THADA) in the cardiac glycoside-induced anti-cancer effect.","authors":"Mizuki Katoh, Takuto Fujii, Yoshiaki Tabuchi, Takahiro Shimizu, Hideki Sakai","doi":"10.1186/s12576-024-00914-7","DOIUrl":"10.1186/s12576-024-00914-7","url":null,"abstract":"<p><p>Cardiac glycosides, known as inhibitors of Na<sup>+</sup>,K<sup>+</sup>-ATPase, have anti-cancer effects such as suppression of cancer cell proliferation and induction of cancer cell death. Here, we examined the signaling pathway elicited by cardiac glycosides in the human hepatocellular carcinoma HepG2 cells and human epidermoid carcinoma KB cells. Three kinds of cardiac glycosides (ouabain, oleandrin, and digoxin) inhibited the cancer cell proliferation and decreased the expression level of thyroid adenoma-associated protein (THADA). Interestingly, the knockdown of THADA inhibited cancer cell proliferation, and the proliferation was significantly rescued by re-expression of THADA in the THADA-knockdown cells. In addition, the THADA-knockdown markedly decreased the expression level of L-type amino acid transporter LAT1. Cardiac glycosides also reduced the LAT1 expression. The LAT1 inhibitor, JPH203, significantly weakened the cancer cell proliferation. These results suggest that the binding of cardiac glycosides to Na<sup>+</sup>,K<sup>+</sup>-ATPase negatively regulates the THADA-LAT1 pathway, exerting the anti-proliferative effect in cancer cells.</p>","PeriodicalId":16832,"journal":{"name":"Journal of Physiological Sciences","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10985892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140336085","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
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