keyword
https://read.qxmd.com/read/37321139/high-resolution-cryo-em-structures-of-trpc5-g%C3%AE-i3-complexes-reveal-direct-activation-of-an-ion-channel-by-g%C3%AE-i-gtp
#21
JOURNAL ARTICLE
Michael X Zhu
Transient receptor potential canonical 4 and 5 (TRPC4 and TRPC5) are Ca2+ -permeable nonselective cation channels known to be activated by Gi/o proteins. Recently, Won et al. (Nat Commun. 2023, 14:2550) reported the cryo-EM structures of TRPC5 in complex with Gαi3 . The G protein alpha subunit was found to directly bind to an ankyrin-like repeat domain in the periphery of the cytosolic portion of TRPC5 some 50 Å away from the membrane. This establishes the TRPC4/C5 ion channels as true effectors of Gα subunits, although the channel gating still depends on the coexistence of Ca2+ and phosphatidylinositol 4,5-bisphosphate...
June 13, 2023: Cell Calcium
https://read.qxmd.com/read/37298241/immunohistochemistry-reveals-trpc-channels-in-the-human-hearing-organ-a-novel-ct-guided-approach-to-the-cochlea
#22
JOURNAL ARTICLE
Colya N Englisch, Jakob Steinhäuser, Silke Wemmert, Martin Jung, Joshua Gawlitza, Gentiana Wenzel, Bernhard Schick, Thomas Tschernig
TRPC channels are critical players in cochlear hair cells and sensory neurons, as demonstrated in animal experiments. However, evidence for TRPC expression in the human cochlea is still lacking. This reflects the logistic and practical difficulties in obtaining human cochleae. The purpose of this study was to detect TRPC6, TRPC5 and TRPC3 in the human cochlea. Temporal bone pairs were excised from ten body donors, and the inner ear was first assessed based on computed tomography scans. Decalcification was then performed using 20% EDTA solutions...
May 26, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/37278959/mir-138-5p-inhibits-thyroid-cancer-cell-growth-and-stemness-by-targeting-trpc5-wnt-%C3%AE-catenin-pathway
#23
JOURNAL ARTICLE
Bo Huang, YiChao Zhang, Peng Sun, YuanYuan Yuan, CunChuan Wang
MicroRNAs play a key role in the pathogenesis of many types of cancer, including thyroid cancer (TC). MiR-138-5p has been confirmed to be abnormally expressed in TC tissues. However, the role of miR-138-5p in TC progression and its potential molecular mechanism need to be further explored. In this study, quantitative real-time PCR was used to examine miR-138-5p and TRPC5 expression, and western blot analysis was performed to examine the protein levels of TRPC5, stemness-related markers, and Wnt pathway-related markers...
June 6, 2023: Molecular Biotechnology
https://read.qxmd.com/read/37265366/insights-into-the-regulation-of-glomerular-filtration-rate-by-the-keap1-nrf2-pathway
#24
JOURNAL ARTICLE
Kengo Kidokoro, Hiroyuki Kadoya, David Z I Cherney, Megumi Kondo, Yoshihisa Wada, Reina Umeno, Seiji Kishi, Hajime Nagasu, Kojiro Nagai, Takafumi Suzuki, Tamaki Sasaki, Masayuki Yamamoto, Yashpal S Kanwar, Naoki Kashihara
BACKGROUND: Literature data suggest that the activation of the Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway increases glomerular filtration rate (GFR) in patients with type 2 diabetes and chronic kidney disease. However, the mechanisms whereby the Keap1-Nrf2 pathway regulates GFR are unknown. Methods: Various renal physiological parameters were assessed in C57BL/6 mice (WT), Nrf2-deficient mice, and Nrf2-activated Keap1-knockdown mice...
June 2, 2023: Kidney360
https://read.qxmd.com/read/37187828/odontoblasts-are-cold-sensory-cells-in-teeth-comment-on-l-bernal-p-sotelo-hitschfeld-c-k%C3%A3-nig-v-sinica-a-wyatt-z-winter-a-hein-f-touska-s-reinhardt-a-tragl-r-kusuda-p-wartenberg-a-sclaroff-j-d-pfeifer-f-ectors-a-dahl-m-freichel-v-vlachova-s-brauchi-c-roza-u
#25
JOURNAL ARTICLE
https://read.qxmd.com/read/37185099/the-sphk1-s1p-axis-regulates-synaptic-vesicle-endocytosis-via-trpc5-channels
#26
JOURNAL ARTICLE
Zhong-Jiao Jiang, Liang-Wei Gong
Sphingosine-1-phosphate (S1P), a bioactive sphingolipid concentrated in the brain, is essential for normal brain functions, such as learning and memory and feeding behaviors. Sphingosine kinase 1 (SphK1), the primary kinase responsible for S1P production in the brain, is abundant within presynaptic terminals, indicating a potential role of the SphK1/S1P axis in presynaptic physiology. Altered S1P levels have been highlighted in many neurologic diseases with endocytic malfunctions. However, it remains unknown whether the SphK1/S1P axis may regulate synaptic vesicle endocytosis in neurons...
May 24, 2023: Journal of Neuroscience
https://read.qxmd.com/read/37174704/long-term-treatment-with-gadopentetic-acid-or-gadodiamide-increases-trpc5-expression-and-decreases-adriamycin-nuclear-accumulation-in-breast-cancer-cells
#27
JOURNAL ARTICLE
Weiheng Zhang, Mengyuan Wang, Weizhen Lv, Fletcher A White, Xingjuan Chen, Alexander G Obukhov
Gadopentetic acid and gadodiamide are paramagnetic gadolinium-based contrast agents (GBCAs) that are routinely used for dynamic contrast-enhanced magnetic resonance imaging (MRI) to monitor disease progression in cancer patients. However, growing evidence indicates that repeated administration of GBCAs may lead to gadolinium (III) cation accumulation in the cortical bone tissue, skin, basal ganglia, and cerebellum, potentially leading to a subsequent slow long-term discharge of Gd3+ . Gd3+ is a known activator of the TRPC5 channel that is implicated in breast cancer's resistance to chemotherapy...
May 3, 2023: Cells
https://read.qxmd.com/read/37137991/molecular-architecture-of-the-g%C3%AE-i-bound-trpc5-ion-channel
#28
JOURNAL ARTICLE
Jongdae Won, Jinsung Kim, Hyeongseop Jeong, Jinhyeong Kim, Shasha Feng, Byeongseok Jeong, Misun Kwak, Juyeon Ko, Wonpil Im, Insuk So, Hyung Ho Lee
G-protein coupled receptors (GPCRs) and ion channels serve as key molecular switches through which extracellular stimuli are transformed into intracellular effects, and it has long been postulated that ion channels are direct effector molecules of the alpha subunit of G-proteins (Gα). However, no complete structural evidence supporting the direct interaction between Gα and ion channels is available. Here, we present the cryo-electron microscopy structures of the human transient receptor potential canonical 5 (TRPC5)-Gαi3 complexes with a 4:4 stoichiometry in lipid nanodiscs...
May 3, 2023: Nature Communications
https://read.qxmd.com/read/37125041/postnatal-nutrition-environment-reprograms-renal-dna-methylation-patterns-in-offspring-of-maternal-protein-restricted-stroke-prone-spontaneously-hypertensive-rats
#29
JOURNAL ARTICLE
Chika Ando, Sihui Ma, Moe Miyoshi, Kyohei Furukawa, Xuguang Li, Huijuan Jia, Hisanori Kato
Maternal malnutrition hampers the offspring health by manipulating the epigenome. Recent studies indicate that the changes in DNA methylation could be reversed by afterbirth nutrition supplementation. In this study, we used DNA methylation arrays to comprehensively investigate the DNA methylation status of the renal promoter regions and the effects of postnatal protein intake on DNA methylation. We fed stroke-prone spontaneously hypertensive (SHRSP) rat dams a normal diet or a low-protein diet during pregnancy, and their 4-week-old male offspring were fed a normal diet or a high-/low-protein diet for 2 weeks...
2023: Frontiers in Nutrition
https://read.qxmd.com/read/37121453/piperlonguminine-attenuates-renal-fibrosis-by-inhibiting-trpc6
#30
JOURNAL ARTICLE
Lei Zhou, Kehan Wu, Yuxuan Gao, Ruizhi Qiao, Na Tang, Dianchao Dong, Xiao-Qiang Li, Qiuna Nong, Ding-Qiang Luo, Qianhan Xiao, Xin Fan, Qimei Duan, Wei Cao
ETHNOPHARMACOLOGICAL RELEVANCE: Liuwei Dihuang (LWDH) is a classic prescription that has been used to the treatment of "Kidney-Yin" deficiency syndrome for more than 1000 years in China. Recent studies have confirmed that LWDH can prevent the progression of renal fibrosis. Numerous studies have demonstrated the critical role that TRPC6 plays in the development of renal fibrosis. Due to the complex composition of LWDH and its remarkable therapeutic effect on renal fibrosis, it is possible to discover new active ingredients targeting TRPC6 for the treatment of renal fibrosis...
April 28, 2023: Journal of Ethnopharmacology
https://read.qxmd.com/read/37102204/clemizole-hydrochloride-a-potent-trpc5-calcium-channel-inhibitor-prevents-cisplatin-induced-nephrotoxicity-in-spraque-dawley-rats
#31
JOURNAL ARTICLE
Meltem Kumaş-Kulualp, Akçahan Gepdiremen, Ersin Karataş, Mukaddes Eşrefoğlu
Cis-diamminedichloroplatinum (II) (cisplatin, Cis) is widely employed to treat several types of cancer. It has many important toxic side effects; one of the most important of which is nephrotoxicity. Clemizole hydrochloride (Clem) as the most potent inhibitor of TRPC5 channels was tested in an animal model of Cis-induced nephrotoxicity. Rats were divided into the following groups: control; Cis (8 mg/kg); Cis + 1 mg/kg Clem; Cis + 5 mg/kg Clem; Cis + 10 mg/kg Clem...
April 26, 2023: Journal of Biochemical and Molecular Toxicology
https://read.qxmd.com/read/37013433/transient-receptor-potential-canonical-5-trpc5-channels-activator-btd-n-3-adamantan-2-yloxy-propyl-3-6-methyl-1-1-dioxo-2h-1%C3%AE-6-2-4-benzothiadiazin-3-yl-propanamide-ameliorates-diabetic-cardiac-autonomic-neuropathy-in-rats
#32
JOURNAL ARTICLE
Pratik Adhya, Shyam Sunder Sharma
BACKGROUND: Diabetic cardiac autonomic neuropathy (DCAN) is a serious diabetic complication with no approved pharmacological agents for its treatment. Parasympathetic system dysfunction characterized by vagal nerve damage is one of the major drivers of DCAN. The TRPC5 or transient receptor potential canonical 5 channel is a promising target in autonomic dysfunction; however, its role in vagal nerve damage and subsequent DCAN has not yet been elucidated. The present study investigated the role of the TRPC5 channel in DCAN using [N-{3-(adamantan-2-yloxy)-propyl}-3-(6-methyl-1,1-dioxo-2H-1λ6,2,4-benzothiadiazin-3-yl) propanamide)] or BTD, which is a potent TRPC5 activator...
April 3, 2023: Current Neurovascular Research
https://read.qxmd.com/read/36948398/from-bench-to-bedside-lessons-learned-from-translational-podocyte-research
#33
JOURNAL ARTICLE
Olivia Lenoir, Tobias B Huber, Pierre-Louis Tharaux
Polat et al. report that mice with a podocyte-specific expression of a constitutively active Rac1 form displayed similar injury and albuminuria, regardless of transient receptor potential canonical 5 activity. This article confirms the pathogenic role of deregulated Rac1 and challenges models involving the role of transient receptor potential canonical 5 in podocytes. We learned from this study and propose a roadmap for this controversial field to help new drug candidates succeed in clinical trials and safely reach patients...
March 21, 2023: Kidney International
https://read.qxmd.com/read/36787370/correction-to-supporting-information-for-ma-et-al-transient-receptor-potential-channel-trpc5-is-essential-for-p-glycoprotein-induction-in-drug-resistant-cancer-cells
#34
JOURNAL ARTICLE
(no author information available yet)
No abstract text is available yet for this article.
February 21, 2023: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/36782471/trp-434-and-trp-435-residues-are-crucial-for-sensing-calcium-ions-and-pi-4-5-p2-molecules-in-trpc5-channel
#35
JOURNAL ARTICLE
Jinhyeong Kim, Jinsung Kim, Insuk So
No abstract text is available yet for this article.
February 10, 2023: Biophysical Journal
https://read.qxmd.com/read/36750145/the-small-gtpase-regulatory-protein-rac1-drives-podocyte-injury-independent-of-cationic-channel-protein-trpc5
#36
JOURNAL ARTICLE
Onur K Polat, Elena Isaeva, Yashwanth R Sudhini, Brenna Knott, Ke Zhu, Manuel Noben, Varsha Suresh Kumar, Nicole Endlich, Steve Mangos, Tejasree Vallapu Reddy, Beata Samelko, Changli Wei, Mehmet M Altintas, Stuart E Dryer, Sanja Sever, Alexander Staruschenko, Jochen Reiser
Transient receptor potential canonical channels (TRPCs) are non-selective cationic channels that play a role in signal transduction, especially in G -protein-mediated signaling cascades. TRPC5 is expressed predominantly in the brain but also in the kidney. However, its role in kidney physiology and pathophysiology is controversial. Some studies have suggested that TRPC5 drives podocyte injury and proteinuria, particularly after small GTPase Rac1 activation to induce the trafficking of TRPC5 to the plasma membrane...
February 5, 2023: Kidney International
https://read.qxmd.com/read/36594388/-expression-and-role-of-the-trpc-family-in-tgf-%C3%AE-1-induced-calcium-influx-in-podocytes
#37
JOURNAL ARTICLE
Hai-Ting Huang, Xu Lin, Peng-Wei Guo, Jun Pang, Jing Ma, Lin-Lin He, Xin-Tong Zheng
The TRPC family consists of multiple important cationic channels in mammals that participate in a variety of physiological and pathological processes. Our previous studies have shown that transforming growth factor-β1 (TGF-β1) increases the expression of TRPC6 in podocytes, but the roles of other members of the TRPC family in podocytes require further investigation. In this study, we investigated the effect of TGF-β1 on the expression of the TRPC family and the role of the TRPC family in the changes of the intracellular Ca2+ concentration ([Ca2+ ]i ) in podocytes induced by TGF-β1...
December 25, 2022: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://read.qxmd.com/read/36564027/histone-lactylation-driven-by-mros-mediated-glycolytic-shift-promotes-hypoxic-pulmonary-hypertension
#38
JOURNAL ARTICLE
Jian Chen, Meiling Zhang, Yanjie Liu, Shihong Zhao, Yanxia Wang, Meng Wang, Wen Niu, Faguang Jin, Zhichao Li
Increased mitochondrial reactive oxygen species (mROS) and glycolysis have been established in pulmonary hypertension (PH). However, the effect of elevated mROS on glycolytic shift and how increased glycolysis promotes hypoxic pulmonary artery smooth muscle cell (PASMC) proliferation and vascular remodeling remain elusive. Here, we reported that hypoxia-induced mROS inhibit HIF-1α hydroxylation and further trigger PASMC glycolytic switch through the upregulated HIF-1α/PDK1&PDK2/p-PDH-E1α axis, which facilitates lactate accumulation and histone lactylation...
April 20, 2023: Journal of Molecular Cell Biology
https://read.qxmd.com/read/36504050/-overexpression-of-mir-607-inhibits-hepatocellular-carcinoma-cell-growth-and-metastasis-by-down-regulating-trpc5
#39
JOURNAL ARTICLE
C Li, S Chen, Y Jiang
OBJECTIVE: To investigate the clinical implications of abnormal expression of miR-607 in hepatocellular carcinoma (HCC) and its influence on HCC cell proliferation and migration. METHODS: The expression of miR-607 in 45 pairs of HCC and adjacent tissues were detected with real-time PCR, and the correlation between miR-607 expression and clinicopathological features of the patients was analyzed. The effects of transfection with miR-607 mimics on proliferation, apoptosis, migration and invasion of two HCC cell lines (Huh-7 and HCCLM3) were evaluated using CCK-8 assay, flow cytometry, wound-healing assay and Transwell assay...
November 20, 2022: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://read.qxmd.com/read/36323681/systematic-analysis-and-prediction-of-genes-associated-with-monogenic-disorders-on-human-chromosome-x
#40
JOURNAL ARTICLE
Elsa Leitão, Christopher Schröder, Ilaria Parenti, Carine Dalle, Agnès Rastetter, Theresa Kühnel, Alma Kuechler, Sabine Kaya, Bénédicte Gérard, Elise Schaefer, Caroline Nava, Nathalie Drouot, Camille Engel, Juliette Piard, Bénédicte Duban-Bedu, Laurent Villard, Alexander P A Stegmann, Els K Vanhoutte, Job A J Verdonschot, Frank J Kaiser, Frédéric Tran Mau-Them, Marcello Scala, Pasquale Striano, Suzanna G M Frints, Emanuela Argilli, Elliott H Sherr, Fikret Elder, Julien Buratti, Boris Keren, Cyril Mignot, Delphine Héron, Jean-Louis Mandel, Jozef Gecz, Vera M Kalscheuer, Bernhard Horsthemke, Amélie Piton, Christel Depienne
Disease gene discovery on chromosome (chr) X is challenging owing to its unique modes of inheritance. We undertook a systematic analysis of human chrX genes. We observe a higher proportion of disorder-associated genes and an enrichment of genes involved in cognition, language, and seizures on chrX compared to autosomes. We analyze gene constraints, exon and promoter conservation, expression, and paralogues, and report 127 genes sharing one or more attributes with known chrX disorder genes. Using machine learning classifiers trained to distinguish disease-associated from dispensable genes, we classify 247 genes, including 115 of the 127, as having high probability of being disease-associated...
November 2, 2022: Nature Communications
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