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Hypercalciuria switches Ca^(2+) signaling in proximal tubular cells,induces oxidative damage to promote calcium nephrolithiasis

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Genes & Diseases 2022年第2期9卷 531-548页

作者： Samuel Shin Cliff-Lawrence Ibeh Eugenia Awuah Boadi Bok-Eum Choi Sanjit K.Roy Bidhan C.Bandyopadhyay calcium signaling Laboratory Research ServiceVeterans Affairs Medical Center50 Irving StreetNWWashingtonDC 20422USA

Proximal tubule(PT)transports most of the renal Ca^(2+),which was usually described as paracellular(passive).We found a regulated Ca^(2+)entry pathway in PT cells via the apical transient receptor potential canonical 3(TRPC3)channel,which initiates transcellular Ca^(2+)*** TRPC3 knockout(−/−)mice were mildly hypercalciuric and displayed luminal calcium phosphate(CaP)crystals at Loop of Henle(LOH),no CaP+calcium oxalate(CaOx)mixed urine crystals were spotted,which are mostly found in calcium nephrolithiasis(CaNL).Thus,we used oral calcium gluconate(CaG;2%)to raise the PT luminal[Ca^(2+)]o further in TRPC3−/−mice for developing such mixed stones to understand the mechanistic role of PT-Ca^(2+)signaling in ***,CaG-treated mice urine samples presented with numerous mixed crystals with remains of PT cells,which were pronounced in TRPC3−/−mice,indicating PT cell ***,PT cells from CaG-treated groups switched their mode of Ca^(2+)entry from receptor-operated to store-operated pathway with a sustained rise in intracellular[Ca^(2+)]([Ca^(2+)]i),indicating the stagnation in PT Ca^(2+)***,those PT cells from CaG-treated groups demonstrated an upregulation of calcification,inflammation,fibrotic,oxidative stress,and apoptotic genes;effects of which were more robust in TRPC3 ablated ***,kidneys from CaG-treated groups exhibited fibrosis,tubular injury and calcifications with significant reactive oxygen species generation in the urine,thus,indicating in vivo *** together,excess PT luminal Ca^(2+)due to escalation of hypercalciuria in TRPC3 ablated mice induced surplus CaP crystal formation and caused stagnation of PT[Ca^(2+)]i,invoking PT cell injury,hence mixed stone formation.

关键词： Apoptosis Ca^(2+)þsignaling calcium nephrolithiasis Chronic kidney disease Fibrosis Hypercalciuria Inflammation Oxidative stress

Confounding risk factors and preventative measures driving nephrolithiasis global makeup

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World Journal of Nephrology 2018年第7期7卷 129-142页

作者： Samuel Shin Aneil Srivastava Nazira A Alli Bidhan C Bandyopadhyay calcium signaling Laboratory Research Service Veterans Affairs Medical Center Washington DC 20422 United States George Washington University Washington DC 20052 United States

Nephrolithiasis is increasing in developed and developing countries at an alarming rate. With the global spike in kidney stone diseases, it is crucial to determine what risk factors are influencing the current global landscape for kidney stones. Our aims for this review are: to identity and analyze the four categories of risk factors in contributing to the global scale of stone formation: lifestyle, genetics, diet, and environment; and discuss preventative measures for kidney stone formation. We also performed data search through the published scientific literature, i.e., PubMed~? and found that there is a significant link between lifestyle and obesity with cases of calcium stones. Food and Agriculture Organization of the United Nations and World Health Organization factor indicators for dietary intake and obesity, along with climate data were used to create the projected total risk world map model for nephrolithiasis risk. Complete global analyses of nephrolithiasis deplete of generalizations is nearly insurmountable due to limited sources of medical and demographic information, but we hope this review can provide further elucidation into confounding risk factors and preventative measures for global nephrolithiasis analysis.

关键词： Nephrolithiasis Epidemiology Risk factors Global factors

Structure-activity relationship of cyclic ADP-ribose, an update

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Journal of Chinese Pharmaceutical Sciences 2013年第2期22卷 127-136页

作者： Andreas H. Guse The calcium Signalling Group Department of Biochemistry and Signal Transduction and Department of Biochemistry and Molecular Cell Biology University Medical Center Hamburg-Eppendorf

Cyclic ADP-ribose (cADPR) is a universal Ca2+ mobilizing second messenger in many different cell types and organisms. cADPR activates Ca2+ release from endo/sarcoplasmic reticulum via ryanodine receptors. In addition, Ca2+ entry secondary to Ca2+ depletion is at least one of the mechanisms in which cADPR triggers Ca2+ inflow, too. Analogues of cADPR have been prepared by chemical and chemo-enzymatic routes. Most of the analogues were analyzed for biological activity in intact or permeabilized Jurkat T cells (a human T-lymphoma cell line). As a systematic approach, analogues were grouped according to alterations in the base, the northern ribose, the southern ribose, the pyrophosphate backbone, or in complex modifications, comprising more than one part of the molecule. Biological activity of the analogues is reviewed, with special emphasis on Jurkat T cells.

关键词： Cyclic ADP-ribose calcium signaling Cyclic ADP-ribose analogue Ryanodine receptor TRPM2 Cellular signal transduction

CD5 expression promotes IL-10 production through activation of the MAPK/Erk pathway and upregulation of TRPC1 channels in B lymphocytes

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Cellular & Molecular Immunology 2018年第2期15卷 158-170页

作者： Soizic Garaud Taher E Taher Marjolaine Debant Miguel Burgos Sarra Melayah Christian Berthou Kaushal Parikh Jacques-Olivier Pers Damien Luque-Paz Gilles Chiocchia Maikel Peppelenbosch David A Isenberg Pierre Youinou Olivier Mignen Yves Renaudineau Rizgar A Mageed INSERM ERI29/EA2216 réseau epigenetique and réseau canaux ioniques du Cancéropôle Grand OuestBrest University Medical SchoolBrest29609France Centre for Experimental Medicine and Rheumatology William Harvey Research InstituteBarts and the London School of Medicine and DentistryQueen Mary University of LondonLondonEC1M 6BQUK canalopathy and calcium signaling INSERM UMR1078Brest29238France Centre for Experimental and Molecular Medicine Academic Medical CenterMeibergdreef 9Amsterdam1105 AZThe Netherlands Laboratory of Immunology and Immunotherapy CHU MorvanBrest29609France Institut Cochin INSERM U567Paris75014France Department of Gastroenterology and Hepatology Erasmus MCGravendijkwal 230Rotterdam015 CERotterdamThe Netherlands Centre for Rheumatology University College LondonLondonWC1E 6JFUK

CD5 is constitutively expressed on T cells and a subset of mature normal and leukemic B cells in patients with chronic lymphocytic leukemia(CLL).Important functional properties are associated with CD5 expression in B cells,including signal transducer and activator of transcription 3 activation,IL-10 production and the promotion of B-lymphocyte survival and ***,the pathway(s)by which CD5 influences the biology of B cells and its dependence on B-cell receptor(BCR)co-signaling remain *** this study,we show that CD5 expression activates a number of important signaling pathways,including Erk1/2,leading to IL-10 production through a novel pathway independent of BCR *** pathway is dependent on extracellular calcium(Ca2+)entry facilitated by upregulation of the transient receptor potential channel 1(TRPC1)*** also show that Erk1/2 activation in a subgroup of CLL patients is associated with TRPC1 *** this subgroup of CLL patients,small inhibitory RNA(siRNA)for CD5 reduces TRPC1 ***,siRNAs for CD5 or for TRPC1 inhibit IL-10 *** findings provide new insights into the role of CD5 in B-cell biology in health and disease and could pave the way for new treatment strategies for patients with B-CLL.

关键词： B cells calcium CD5 MAPK/Erk TRPC1

Rumex acetosella Inhibits Platelet Function via Impaired MAPK and Phosphoinositide 3-Kinase signaling

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Chinese Journal of Integrative Medicine 2022年第9期28卷 802-808页

作者： Bo-Ra Jeon Muhammad Irfan Seung Eun Lee Jeong Hoon Lee Man Hee Rhee Laboratory of Physiology and Cell signaling College of Veterinary MedicineKyungpook National UniversityDaegu41566Republic of Korea Department of Herbal Crop Research National Institute of Horticultural and Herbal Science(NIHHS)Eumseong27709Republic of Korea

Objective:To examine the antiplatelet and antithrombotic activity of Rumex acetosella ***:Standard light aggregometry was used for platelet aggregation,intracellular calcium mobilization assessed using Fura-2/AM,granule secretion(ATP release)by luminometer,and fibrinogen binding to integrin α_(Ⅱb)β_(3) detected using flow *** blotting is carried out to determine the phosphorylation of mitogen-activated protein kinase(MAPK)and phosphoinositide 3-kinase(PI3K)/Akt ***:Rumex acetosella displayed the ability to inhibit platelet aggregation,calcium mobilization,granule secretion,and fibrinogen binding to integrin α_(Ⅱb)β_(3).Rumex acetosella has also down-regulated MAPK and PI3K/Akt phosphorylation(all Psignaling,and it may protect against the development of platelet-related cardiovascular diseases.

关键词： antiplatelet ethnomedicine integrinα_(Ⅱb)β_(3) mitogen-activated protein kinase Rumex acetosella L.

Schizonepeta tenuifolia inhibits collagen stimulated platelet function via suppressing MAPK and Akt signaling

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The Journal of Biomedical Research 2019年第4期33卷 250-257页

作者： Bo-Ra Jeon Muhammad Irfan Minki Kim Seung Eun Lee Jeong Hoon Lee Man Hee Rhee Laboratory of Physiology and Cell signaling College of Veterinary MedicineKyungpook National UniversityDaegu 41566Republic of Korea Department of Herbal Crop Research National Institute of Horticultural and Herbal ScienceEumseong 27709Republic of Korea.

The prevalence of cardiovascular diseases(CVDs)is increasing at a rapid pace in developed countries,and CVDs are the leading cause of morbidity and *** products and ethnomedicine have been shown to reduce the risk of ***(S.)tenuifolia is a medicinal plant widely used in China,Korea,and Japan and is known to exhibit anti-inflammatory,antioxidant,and immunomodulatory *** hypothesized that given herbal plant exhibit pharmacological activities against CVDs,we specifically explored its effects on platelet *** aggregation was evaluated using standard light transmission *** calcium mobilization was assessed using Fura-2/AM,and granule secretion(ATP release)was measured in a *** binding to integrin a_(Ⅱb)β_3,was assessed using flow *** of mitogen-activated protein kinase(MAPK)signaling molecules and activation of the protein kinase B(Akt)was assessed using Western blot ***,extract potently and significantly inhibited platelet aggregation,calcium mobilization,granule secretion,and fibrinogen binding to integrin a_(Ⅱb)β_***,all extracts significantly inhibited MAPK and Akt *** extract inhibited platelet aggregation and granule secretion,and attenuated collagen mediated GPVI downstream signaling,indicating the potential therapeutic effects of these plant extracts on the cardiovascular system and platelet *** suggest that *** extract may be a potent candidate to treat platelet-related CVDs and to be used as an antiplatelet and antithrombotic agent.

关键词： S.tenuifolia platelet MAPK Akt natural antithrombotic agent

Transient receptor potential vanilloid 4-dependent calcium influx and ATP release in mouse and rat gastric epithelia

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World Journal of Gastroenterology 2016年第24期22卷 5512-5519页

作者： Hiroshi Mihara Nobuhiro Suzuki Ammar Abdullkader Boudaka Jibran Sualeh Muhammad Makoto Tominaga Yoshiaki Tabuchi Toshiro Sugiyama Department of Gastroenterology Graduate School of Medicine and Pharmaceutical Sciences University of Toyama Division of Cell signaling Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences) National Institutes of Natural Sciences Department of Physiology College of Medicine and Health Sciences Sultan Qaboos University Life Science Research Center University of Toyama

AIM: To explore the expression of transient receptor potential vanilloid 4(TRPV4) and its physiological meaning in mouse and rat gastric epithelia. METHODS: RT-PCR and immunochemistry were used to detect TRPV4 m RNA and protein expression in mouse stomach and a rat normal gastric epithelial cell line(RGE1-01), while Ca2+-imaging and electrophysiology were used to evaluate TRPV4 channel activity. ATP release was measured by a luciferin-luciferase assay. Gastric emptying was also compared between WT and TRPV4 knockout mice. RESULTS: TRPV4 m RNA and protein were detected in mouse tissues and RGE1-01 cells. A TRPV4-specific agonist(GSK1016790A) increased intracellular Ca2+ concentrations and/or evoked TRPV4-like current activities in WT mouse gastric epithelial cells andRGE1-01 cells, but not TRPV4 KO cells. GSK1016790 A or mechanical stimuli induced ATP release from RGE1-01 cells while TRPV4 knockout mice displayed delayed gastric emptying in vivo. CONCLUSION: TRPV4 is expressed in mouse and rat gastric epithelium and contributes to ATP release and gastric emptying.

关键词： Transient receptor potential vanilloid 4 Stomach gastric emptying ATP

Pinetonina<sup>TM</sup>, an Intranasally Administered Essential Oil Preparation, Is Effective in Decrease of Cortisol Levels and on the Glutamate Release Modulation

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Neuroscience & Medicine 2018年第3期9卷 135-149页

作者： Maira Jardim Fernando Amaral Valeria Maria de Souza Antunes Fernando Rodrigues Mariana Soares Alves de Souza Fernanda Rossi Siqueto Luiza Melanie Silva Rafaela Alves Bertolino Victor Cavalaro Carlos Rocha Oliveira Institute of Osmology and Essential Oils Camanducaia Brazil Group of Fitocomplexes and Cellular signaling School of Health Science Anhembi Morumbi University S&#227 o Paulo Brazil University of Anhembi Morumbi S&#227 o Paulo Brazil Institute of Osmology and Essential Oils Minas Gerais Brazil and Group of Fitocomplexes and Cellular Signaling School of Health Science Anhembi Morumbi University S&#227 o Paulo Brazil

Background: Most anxiety complaints are treated with pharmacological measures involving barbiturates and benzodiazepines, in which they may end up causing tolerance and pharmacological dependence. Integrative approaches such as aromatherapy are used in addition to medications to improve sleep quality and reduce anxiety. Thus, PinetoninTM, a phytocomplex obtained from a blend of essential oils aims to aid in the symptoms of stress and anxiety. Methods: The cytotoxicity of PinetoninTM was evaluated MTT assay using fibroblasts and astrocytes showed reduction in the cell viability only at high concentrations. Evaluation of intracellular calcium and determination of residual glutamate in the supernatant of astrocyte cultures showed agonist action of dihydroxyphenylglycine (DHPG) increasing linearly the concentration of intracellular calcium and the glutamate levels in the supernatants of the cultures. On the other hand, cultures of astrocytes treated with PinetoninTM showed residual glutamate levels in the supernatants reducing proportionally, as well as, intracellular calcium reduction. The determination of salivary cortisol showed a significant reduction in salivary cortisol levels in the group that received PinetoninTM. The evaluation of the electroencephalogram in patients treated with PinetoninTM had a significant increase (P Results: A reduction in dose-dependent cell viability was observed when compared to cultures of PinetoninTM treated fibroblasts with control culture. When PinetoninTM and linole are administered in astrocytic cells, there was a reduction of the intracellular concentration of Ca2+ against a control group treated with DHPG agonist. The evaluation of salivary cortisol demonstrated a reduction when the patient group was treated with PinetoninTM by purchasing the results against the group of patients treated with saline. Reinforcing the relaxed state of that group, alpha waves have been increased and reductions in beta waves. Conclusion: The results

关键词： Pinetonin Anxiety Cortisol Astrocites Glutamate

Artemisia vulgaris Induces Tumor-Selective Ferroptosis and Necroptosis via Lysosomal Ca^(2+) signaling

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Chinese Journal of Integrative Medicine 2024年第6期30卷 525-533页

作者： Lucas dos Santos Zamarioli Michele Rosana Maia Santos Adolfo Garcia Erustes Vanessa Marques Meccatti Thais Cristine Pereira Soraya S Smaili Maria Cristina Marcucci Carlos Rocha Oliveira Gustavo JS Pereira Claudia Bincoletto Department of Pharmacology Paulista School of MedicineFederal University of São PauloSão PauloSP04044-020Brazil Research Group on Phytocomplexes and Cell signaling School of Health SciencesAnhembi Morumbi UniversitySão PauloSP03164-000Brazil Department of Biosciences and Oral Diagnosis Institute of Science and TechnologySão Paulo State University(ICT-UNESP)São PauloSP12231-280Brazil

Objective To evaluate the chemical composition and effects of Artemisia vulgaris(AV)hydroalcoholic extract(HEAV)on breast cancer cells(MCF-7 and SKBR-3),chronic myeloid leukemia(K562)and NIH/3T3 *** Phytochemical analysis of HEAV was done by high-performance liquid chromatography-mass(HPLC)*** and cell death studies were performed using trypan blue and Annexin/FITC-7AAD,***-1(Fer-1)and necrostatin-1(Nec-1)were used to assess the mode of HEAV-induced cell death and acetoxymethylester(BAPTA-AM)was used to verify the involvement of cytosolic calcium in this *** calcium measurements were made using *** HEAV decreased the viability of MCF-7,SKBR-3 and K562 cells(P<0.05).The viability of HEAV-treated K562 cells was reduced compared to HEAV-exposed fibroblasts(P<0.05).Treatment of K562 cells with HEAV induced cell death primarily by late apoptosis and necrosis in assays using annexin V-FITC/7-AAD(P<0.05).The use of Nec-1 and Fer-1 increased the viability of K562 cells treated with HEAV relative to cells exposed to HEAV alone(P<0.01).HEAV-induced Ca^(2+)release mainly from lysosomes in K562 cells(P<0.01).Furthermore,BAPTA-AM,an intracellular Ca^(2+)chelator,decreased the number of non-viable cells treated with HEAV(P<0.05).Conclusions HEAV is cytotoxic and activates several modalities of cell death,which are partially dependent on lysosomal release of Ca^(2+).These effects may be related to artemisinin and caffeoylquinic acids,the main compounds identified in HEAV.

关键词： Artemisia vulgaris necroptosis ferroptosis late apoptosis Ca^(2+)signaling