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Article ; Online: Patchouli alcohol induces G

Liang, Chi-Yen / Chang, Kai-Fu / Huang, Ya-Chih / Huang, Xiao-Fan / Sheu, Gwo-Tarng / Kuo, Chia-Feng / Hsiao, Chih-Yen / Tsai, Nu-Man

Thoracic cancer

2023 Volume 14, Issue 21, Page(s) 2007–2017

Abstract: ... forming abilities and induced cell cycle arrest at the G: Conclusions: PA induced ROS-mediated DNA ...

Abstract	Background: Lung cancer, especially non-small cell lung cancer (NSCLC), is one of the leading causes of cancer-related deaths worldwide. Vincristine (VCR) is a chemotherapeutic agent for lung cancers; however, its effectiveness is limited by side effects and the development of drug resistance. Patchouli alcohol (PA), from Pogostemon cablin extract, is known to possess anti-inflammatory and anticancer properties. In this study, we investigated the role of PA in inducing reactive oxygen species (ROS)-mediated DNA damage in A549 and VCR-resistant A549/V16 NSCLC cells. Methods: The anticancer potential of PA was studied using the MTT assay, colony formation, flow cytometry analysis, western blotting, DCFDA staining, immunofluorescence staining, and TUNEL assay techniques. Results: The intracellular ROS levels were enhanced in PA-treated cells, activating the CHK1 and CHK2 signaling pathways. PA further inhibited proliferation and colony-forming abilities and induced cell cycle arrest at the G Conclusions: PA induced ROS-mediated DNA damage, triggered cell cycle arrest and apoptosis, attenuated drug resistance and cancer stem cell phenotypes, and synergistically inhibited proliferation in combination with cisplatin. These findings suggest that PA has the potential to be used for the treatment of NSCLC with or without VCR resistance.
MeSH term(s)	Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/metabolism ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism ; Vincristine ; Reactive Oxygen Species/metabolism ; Cisplatin/therapeutic use ; Cell Line, Tumor ; Cell Cycle Checkpoints ; Apoptosis ; DNA Damage ; Cell Proliferation
Chemical Substances	Vincristine (5J49Q6B70F) ; patchouli alcohol (HHH8CPR1M2) ; Reactive Oxygen Species ; Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2023-05-30
Publishing country	Singapore
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2625856-0
ISSN	1759-7714 ; 1759-7706
ISSN (online)	1759-7714
ISSN	1759-7706
DOI	10.1111/1759-7714.14982
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Zs.A 6921: Show issues

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Article ; Online: Constructing B─N─P Bonds in Ultrathin Holey g-C

Hussien, Mahmoud Kamal / Sabbah, Amr / Qorbani, Mohammad / Putikam, Raghunath / Kholimatussadiah, Septia / Tzou, Der-Lii M / Elsayed, Mohamed Hammad / Lu, Yu-Jung / Wang, Yen-Yu / Lee, Xing-Hao / Lin, Tsai-Yu / Thang, Nguyen Quoc / Wu, Heng-Liang / Haw, Shu-Chih / Wu, Kevin C-W / Lin, Ming-Chang / Chen, Kuei-Hsien / Chen, Li-Chyong

Small (Weinheim an der Bergstrasse, Germany)

2024 , Page(s) e2400724

Abstract: The lack of intrinsic active sites for photocatalytic ... ...

Abstract	The lack of intrinsic active sites for photocatalytic CO
Language	English
Publishing date	2024-04-19
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2168935-0
ISSN	1613-6829 ; 1613-6810
ISSN (online)	1613-6829
ISSN	1613-6810
DOI	10.1002/smll.202400724
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Article ; Online: Total synthesis of aspidostomide G from a brominated tryptamine.

Wu, Bo-You / Shih, Fang-Yi / Tsai, Yu-Tung / Chu, Chia-Yen / Lin, Cheng-Kun

Organic & biomolecular chemistry

2023 Volume 21, Issue 22, Page(s) 4601–4605

Abstract: The first total synthesis of aspidostomide G using a brominated tryptamine is described ...

Abstract	The first total synthesis of aspidostomide G using a brominated tryptamine is described. The synthetic route features several notable aspects: (a) the starting material, compound 13, contains a built-in hydroxy group and was transformed to the Sonogashira reaction precursor; (b) the construction of the indole ring was achieved through a transition-metal catalyzed synthesis and a 5-
Language	English
Publishing date	2023-06-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2097583-1
ISSN	1477-0539 ; 1477-0520
ISSN (online)	1477-0539
ISSN	1477-0520
DOI	10.1039/d3ob00672g
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Article: Preparation of a stable CCL5·CCR5·G

Isaikina, Polina / Tsai, Ching-Ju / Petrovic, Ivana / Rogowski, Marco / Dürr, Alexandra Meng / Grzesiek, Stephan

Methods in cell biology

2022 Volume 169, Page(s) 115–141

Abstract: The numerous chemokines and their cognate G protein-coupled chemokine receptors on the surface ... in its active conformation bound to the chemokine super-agonist [6P4]CCL5 and the heterotrimeric G ...

Abstract	The numerous chemokines and their cognate G protein-coupled chemokine receptors on the surface of leukocytes form a complex signaling network, which regulates the immune response and also other key physiological processes. Currently only a very limited number of structures of chemokine•chemokine receptor complexes have been solved. More structures are needed for the understanding of their mechanism of action and the rational design of drugs against these highly relevant therapeutic targets. Recently, we have determined the cryo-EM structure of the human wild-type CCR5 chemokine receptor, which is also the HIV-1 coreceptor, in its active conformation bound to the chemokine super-agonist [6P4]CCL5 and the heterotrimeric G
MeSH term(s)	Chemokine CCL5/chemistry ; Chemokines/metabolism ; Cryoelectron Microscopy ; Humans ; Receptors, CCR5/chemistry ; Receptors, CCR5/metabolism ; Receptors, G-Protein-Coupled ; Signal Transduction
Chemical Substances	CCL5 protein, human ; CCR5 protein, human ; Chemokine CCL5 ; Chemokines ; Receptors, CCR5 ; Receptors, G-Protein-Coupled
Language	English
Publishing date	2022-04-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	0091-679X
ISSN	0091-679X
DOI	10.1016/bs.mcb.2022.03.001
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Article ; Online: Biochemical Characterization of GPCR-G Protein Complex Formation.

Pamula, Filip / Tsai, Ching-Ju

Methods in molecular biology (Clifton, N.J.)

2021 Volume 2302, Page(s) 37–48

Abstract: The complex of G protein-coupled receptors (GPCR) and G proteins is the core assembly in GPCR ... growth in structures of GPCR-G protein complexes solved to near-atomic resolution, giving important ... between GPCRs and G proteins before preparation of GPCR-G protein complexes for structural studies. We use ...

Abstract	The complex of G protein-coupled receptors (GPCR) and G proteins is the core assembly in GPCR signaling in eukaryotes. With the recent development of cryo-electron microscopy, there has been a rapid growth in structures of GPCR-G protein complexes solved to near-atomic resolution, giving important insights into this signaling complex. Here we describe the biochemical protocol to study the interaction between GPCRs and G proteins before preparation of GPCR-G protein complexes for structural studies. We use gel filtration to analyze the binding properties between GPCR and G protein with the presence of agonist or antagonist, as well as the complex dissociation in the presence of GTP analogue. Methods used in the protocol are affinity purification and gel filtration, which are also commonly used in protein sample preparation for structural work. Therefore, the protocol can be easily adapted for large-scale sample preparation.
MeSH term(s)	Cell Membrane/metabolism ; Chromatography, Gel ; GTP-Binding Proteins/chemistry ; GTP-Binding Proteins/metabolism ; Guanosine Triphosphate/analogs & derivatives ; HEK293 Cells ; Humans ; Protein Binding ; Receptors, G-Protein-Coupled/chemistry ; Receptors, G-Protein-Coupled/metabolism ; Signal Transduction
Chemical Substances	Receptors, G-Protein-Coupled ; Guanosine Triphosphate (86-01-1) ; GTP-Binding Proteins (EC 3.6.1.-)
Language	English
Publishing date	2021-04-20
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-1394-8_3
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Article ; Online: Crystal structure of rhodopsin in complex with a mini-G

Tsai, Ching-Ju / Pamula, Filip / Nehmé, Rony / Mühle, Jonas / Weinert, Tobias / Flock, Tilman / Nogly, Przemyslaw / Edwards, Patricia C / Carpenter, Byron / Gruhl, Thomas / Ma, Pikyee / Deupi, Xavier / Standfuss, Jörg / Tate, Christopher G / Schertler, Gebhard F X

Science advances

2018 Volume 4, Issue 9, Page(s) eaat7052

Abstract: Selective coupling of G protein (heterotrimeric guanine nucleotide-binding protein)-coupled ... the formation of a signaling complex between the receptor and G protein. We report the crystal structure ... of light-sensitive GPCR rhodopsin bound to an engineered mini-G ...

Abstract	Selective coupling of G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptors (GPCRs) to specific Gα-protein subtypes is critical to transform extracellular signals, carried by natural ligands and clinical drugs, into cellular responses. At the center of this transduction event lies the formation of a signaling complex between the receptor and G protein. We report the crystal structure of light-sensitive GPCR rhodopsin bound to an engineered mini-G
MeSH term(s)	Animals ; Binding Sites ; Cattle ; Crystallography, X-Ray ; Models, Molecular ; Multiprotein Complexes/chemistry ; Multiprotein Complexes/metabolism ; Mutation ; Protein Conformation ; Receptors, G-Protein-Coupled/chemistry ; Receptors, G-Protein-Coupled/metabolism ; Rhodopsin/chemistry ; Rhodopsin/genetics ; Rhodopsin/metabolism
Chemical Substances	Multiprotein Complexes ; Receptors, G-Protein-Coupled ; Rhodopsin (9009-81-8)
Language	English
Publishing date	2018-09-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.aat7052
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Article ; Online: TERRA regulates DNA G-quadruplex formation and ATRX recruitment to chromatin.

Tsai, Ru-Xuan / Fang, Kuo-Chen / Yang, Po-Cheng / Hsieh, Yu-Hung / Chiang, I-Tien / Chen, Yunfei / Lee, Hun-Goo / Lee, Jeannie T / Chu, Hsueh-Ping Catherine

Nucleic acids research

2022

Abstract: The genome consists of non-B-DNA structures such as G-quadruplexes (G4) that are involved ... of folding into G-quadruplex and interacting with chromatin remodeler ATRX. Here we show that TERRA modulates ... ATRX occupancy on repetitive sequences and over genes, and maintains DNA G-quadruplex structures ...

Abstract	The genome consists of non-B-DNA structures such as G-quadruplexes (G4) that are involved in the regulation of genome stability and transcription. Telomeric-repeat containing RNA (TERRA) is capable of folding into G-quadruplex and interacting with chromatin remodeler ATRX. Here we show that TERRA modulates ATRX occupancy on repetitive sequences and over genes, and maintains DNA G-quadruplex structures at TERRA target and non-target sites in mouse embryonic stem cells. TERRA prevents ATRX from binding to subtelomeric regions and represses H3K9me3 formation. G4 ChIP-seq reveals that G4 abundance decreases at accessible chromatin regions, particularly at transcription start sites (TSS) after TERRA depletion; such G4 reduction at TSS is associated with elevated ATRX occupancy and differentially expressed genes. Loss of ATRX alleviates the effect of gene repression caused by TERRA depletion. Immunostaining analyses demonstrate that knockdown of TERRA diminishes DNA G4 signals, whereas silencing ATRX elevates G4 formation. Our results uncover an epigenetic regulation by TERRA that sequesters ATRX and preserves DNA G4 structures.
Language	English
Publishing date	2022-11-28
Publishing country	England
Document type	Journal Article
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkac1114
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Zs.A 1067: Show issues

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Article ; Online: Small Activating RNA Modulation of the G Protein-Coupled Receptor for Cancer Treatment.

Xiong, Yunfang / Ke, Ran / Zhang, Qingyu / Lan, Wenjun / Yuan, Wanjun / Chan, Karol Nga Ieng / Roussel, Tom / Jiang, Yifan / Wu, Jing / Liu, Shuai / Wong, Alice Sze Tsai / Shim, Joong Sup / Zhang, Xuanjun / Xie, Ruiyu / Dusetti, Nelson / Iovanna, Juan / Habib, Nagy / Peng, Ling / Lee, Leo Tsz On

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

2022 Volume 9, Issue 26, Page(s) e2200562

Abstract: G protein-coupled receptors (GPCRs) are the most common and important drug targets. However, >70 ...

Abstract	G protein-coupled receptors (GPCRs) are the most common and important drug targets. However, >70% of GPCRs are undruggable or difficult to target using conventional chemical agonists/antagonists. Small nucleic acid molecules, which can sequence-specifically modulate any gene, offer a unique opportunity to effectively expand drug targets, especially those that are undruggable or difficult to address, such as GPCRs. Here, the authors report for the first time that small activating RNAs (saRNAs) effectively modulate a GPCR for cancer treatment. Specifically, saRNAs promoting the expression of Mas receptor (MAS1), a GPCR that counteracts the classical angiotensin II pathway in cancer cell proliferation and migration, are identified. These saRNAs, delivered by an amphiphilic dendrimer vector, enhance MAS1 expression, counteracting the angiotensin II/angiotensin II Receptor Type 1 axis, and leading to significant suppression of tumorigenesis and the inhibition of tumor progression of multiple cancers in tumor-xenografted mouse models and patient-derived tumor models. This study provides not only a new strategy for cancer therapy by targeting the renin-angiotensin system, but also a new avenue to modulate GPCR signaling by RNA activation.
MeSH term(s)	Angiotensin II/metabolism ; Animals ; Mice ; Neoplasms/genetics ; Neoplasms/therapy ; RNA/metabolism ; Receptors, G-Protein-Coupled/genetics ; Renin-Angiotensin System
Chemical Substances	Receptors, G-Protein-Coupled ; Angiotensin II (11128-99-7) ; RNA (63231-63-0)
Language	English
Publishing date	2022-06-16
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2808093-2
ISSN	2198-3844 ; 2198-3844
ISSN (online)	2198-3844
ISSN	2198-3844
DOI	10.1002/advs.202200562
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Article ; Online: High-mass MALDI-MS unravels ligand-mediated G protein-coupling selectivity to GPCRs.

Wu, Na / Olechwier, Agnieszka M / Brunner, Cyrill / Edwards, Patricia C / Tsai, Ching-Ju / Tate, Christopher G / Schertler, Gebhard F X / Schneider, Gisbert / Deupi, Xavier / Zenobi, Renato / Ma, Pikyee

Proceedings of the National Academy of Sciences of the United States of America

2021 Volume 118, Issue 31

Abstract: G protein-coupled receptors (GPCRs) are important pharmaceutical targets for the treatment ... with bound ligands and G proteins, the detailed molecular interplay between the receptors and their signaling ... matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) method to interrogate the first stage of signal transduction. GPCR-G protein ...

Abstract	G protein-coupled receptors (GPCRs) are important pharmaceutical targets for the treatment of a broad spectrum of diseases. Although there are structures of GPCRs in their active conformation with bound ligands and G proteins, the detailed molecular interplay between the receptors and their signaling partners remains challenging to decipher. To address this, we developed a high-sensitivity, high-throughput matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) method to interrogate the first stage of signal transduction. GPCR-G protein complex formation is detected as a proxy for the effect of ligands on GPCR conformation and on coupling selectivity. Over 70 ligand-GPCR-partner protein combinations were studied using as little as 1.25 pmol protein per sample. We determined the selectivity profile and binding affinities of three GPCRs (rhodopsin, beta-1 adrenergic receptor [β1AR], and angiotensin II type 1 receptor) to engineered Gα-proteins (mGs, mGo, mGi, and mGq) and nanobody 80 (Nb80). We found that GPCRs in the absence of ligand can bind mGo, and that the role of the G protein C terminus in GPCR recognition is receptor-specific. We exemplified our quantification method using β1AR and demonstrated the allosteric effect of Nb80 binding in assisting displacement of nadolol to isoprenaline. We also quantified complex formation with wild-type heterotrimeric Gα
MeSH term(s)	Animals ; Arrestin/genetics ; Arrestin/metabolism ; GTP-Binding Proteins/genetics ; GTP-Binding Proteins/metabolism ; Gene Expression Regulation ; HEK293 Cells ; Humans ; Ligands ; Mice ; Models, Molecular ; Protein Binding ; Protein Conformation ; Receptors, Opioid/chemistry ; Receptors, Opioid/metabolism ; Single-Chain Antibodies ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods ; Turkeys ; beta-Arrestin 1/genetics ; beta-Arrestin 1/metabolism
Chemical Substances	Arrestin ; Ligands ; Nb80 nanobody ; Receptors, Opioid ; Single-Chain Antibodies ; beta-Arrestin 1 ; GTP-Binding Proteins (EC 3.6.1.-)
Language	English
Publishing date	2021-07-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2024146118
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Zs.A 1148: Show issues

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Article ; Online: Protective Effects of Sophoraflavanone G by Inhibiting TNF-α-Induced MMP-9-Mediated Events in Brain Microvascular Endothelial Cells.

Lee, Tsong-Hai / Chen, Jiun-Liang / Tsai, Ming-Ming / Wu, Yi-Hsuan / Tseng, Hui-Ching / Cheng, Li-Ching / Shanmugam, Velayuthaprabhu / Hsieh, Hsi-Lung

International journal of molecular sciences

2023 Volume 25, Issue 1

Abstract: ... Among them, a flavonoid compound, sophoraflavanone G (SG), found in ...

Abstract	The regulation of matrix metalloproteinases (MMPs), especially MMP-9, has a critical role in both physiological and pathological events in the central nervous system (CNS). MMP-9 is an indicator of inflammation that triggers several CNS disorders, including neurodegeneration. Tumor necrosis factor-α (TNF-α) has the ability to stimulate the production of different inflammatory factors, including MMP-9, in several conditions. Numerous phytochemicals are hypothesized to mitigate inflammation, including the CNS. Among them, a flavonoid compound, sophoraflavanone G (SG), found in
MeSH term(s)	Animals ; Mice ; Endothelial Cells ; Tumor Necrosis Factor-alpha/pharmacology ; Matrix Metalloproteinase 9 ; Brain ; Inflammation ; Flavanones
Chemical Substances	Tumor Necrosis Factor-alpha ; vexibinol (97938-30-2) ; Matrix Metalloproteinase 9 (EC 3.4.24.35) ; Flavanones
Language	English
Publishing date	2023-12-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25010283
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