Ca<sup>2+</sup>‐dependent down‐regulation of human histamine H<sub>1</sub>receptors in Chinese hamster ovary cells

Hishinuma, Shigeru; Komazaki, Hiroshi; Tsukamoto, Hayato; hatahara, hirokazu; Fukui, Hirokazu; Miyake, Shoji

doi:10.1111/jnc.14245

Cited by 5 publications

(5 citation statements)

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“…Furthermore, in nerve cell clusters, entering Ca 2+ inhibits dynamin and arrests endocytosis 33 . Thus, we examined the role of Ca 2+ in APJ endocytosis using ionomycin, an antibiotic that increases intracellular Ca 2+ , 34 and BAPTA‐AM, a Ca 2+ chelator that decreases intracellular Ca 2+ 35 . Ionomycin induced APJ endocytosis in H9C2 cells, whereas BAPTA‐AM inhibited miR‐204‐induced APJ endocytosis (Figure 6C–F and Figure S7A–C).…”

Section: Resultsmentioning

confidence: 99%

The microRNA‐204‐5p inhibits APJ signalling and confers resistance to cardiac hypertrophy and dysfunction

Gaddam

Kim

Jacobs

et al. 2022

Clinical & Translational Med

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Background MicroRNAs regulate cardiac hypertrophy development, which precedes and predicts the risk of heart failure. microRNA‐204‐5p (miR‐204) is well expressed in cardiomyocytes, but its role in developing cardiac hypertrophy and cardiac dysfunction (CH/CD) remains poorly understood. Methods: We performed RNA‐sequencing, echocardiographic, and molecular/morphometric analysis of the heart of mice lacking or overexpressing miR‐204 five weeks after trans‐aortic constriction (TAC). The neonatal rat cardiomyocytes, H9C2, and HEK293 cells were used to determine the mechanistic role of miR‐204. Results The stretch induces miR‐204 expression, and miR‐204 inhibits the stretch‐induced hypertrophic response of H9C2 cells. The mice lacking miR‐204 displayed a higher susceptibility to CH/CD during pressure overload, which was reversed by the adeno‐associated virus serotype‐9‐mediated cardioselective miR‐204 overexpression. Bioinformatic analysis of the cardiac transcriptomics of miR‐204 knockout mice following pressure overload suggested deregulation of apelin‐receptor (APJ) signalling. We found that the stretch‐induced extracellular signal‐regulated kinase 1/2 (ERK1/2) activation and hypertrophy‐related genes expression depend on the APJ, and both of these effects are subject to miR‐204 levels. The dynamin inhibitor dynasore inhibited both stretch‐induced APJ endocytosis and ERK1/2 activation. In contrast, the miR‐204‐induced APJ endocytosis was neither inhibited by dynamin inhibitors (dynasore and dyngo) nor associated with ERK1/2 activation. We find that the miR‐204 increases the expression of ras‐associated binding proteins (e.g., Rab5a, Rab7) that regulate cellular endocytosis. Conclusions Our results show that miR‐204 regulates trafficking of APJ and confers resistance to pressure overload‐induced CH/CD, and boosting miR‐204 can inhibit the development of CH/CD.

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Section: Resultsmentioning

confidence: 99%

The microRNA‐204‐5p inhibits APJ signalling and confers resistance to cardiac hypertrophy and dysfunction

Gaddam

Kim

Jacobs

et al. 2022

Clinical & Translational Med

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“…The study was not pre-registered and required neither randomization nor blinding. The construction of CHO cells stably expressing HA-tagged wild-type human histamine H 1 receptors (HA-WT) has been described previously [19]. The expression vectors for the Lys191 mutants of HA-WT to alanine (HA-K191A) were constructed using the PrimeSTAR mutagenesis basal kit (Takara Bio, Otsu, Shiga, Japan) and Mastercycler Gradient (Eppendorf, Hamburg, Germany) in 3 × HA hH1R/pcDNA3.1(+), in accordance with the manufacturer’s protocol [20,21].…”

Section: Methodsmentioning

confidence: 99%

Differential Regulation of Thermodynamic Binding Forces of Levocetirizine and (S)-Cetirizine by Lys191 in Human Histamine H1 Receptors

Hishinuma

Tamura

Kobayashi

et al. 2018

IJMS

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Cetirizine is a zwitterionic second-generation antihistamine containing R- and S-enantiomers, levocetirizine, and (S)-cetirizine. Levocetirizine is known to have a higher affinity for the histamine H1 receptors than (S)-cetirizine; ligand-receptor docking simulations have suggested the importance of the formation of a salt bridge (electrostatic interaction) between the carboxylic group of levocetirizine and the Lys191 residue at the fifth transmembrane domain of human histamine H1 receptors. In this study, we evaluated the roles of Lys191 in the regulation of the thermodynamic binding forces of levocetirizine in comparison with (S)-cetirizine. The binding enthalpy and entropy of these compounds were estimated from the van ‘t Hoff equation, by using the dissociation constants obtained from their displacement curves against the binding of [3H]mepyramine to the membrane preparations of Chinese hamster ovary cells expressing wild-type human H1 receptors and their Lys191 mutants to alanine at various temperatures. We found that the higher binding affinity of wild-type H1 receptors for levocetirizine than (S)-cetirizine was achieved by stronger forces of entropy-dependent hydrophobic binding of levocetirizine. The mutation of Lys191 to alanine reduced the affinities for levocetirizine and (S)-cetirizine, through a reduction in the entropy-dependent hydrophobic binding forces of levocetirizine and the enthalpy-dependent electrostatic binding forces of (S)-cetirizine. These results suggested that Lys191 differentially regulates the binding enthalpy and entropy of these enantiomers, and that Lys191 negatively regulates the enthalpy-dependent electrostatic binding forces of levocetirizine, contrary to the predictions derived from the ligand-receptor docking simulations.

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“…Sucrose (SCR) was used to generate a hypertonic medium to disturb the formation of clathrin vesicles on the cell membrane. Under this condition, clathrin-dependent endocytosis is inhibited [16][17][18][19][20][21] . Chlorpromazine (CPZ) was used in this study as an inhibitor of clathrinmediated endocytosis.…”

Section: Drug Treatmentsmentioning

confidence: 99%

“…Considering that the ability of alphaviruses to enter into the host cell via alternative pathways has already been reported [13][14][15]36 , we evaluated the dependence of PIXV and RNV entry into Vero cells by clathrin-mediated endocytosis. To this end, we first employed chemical inhibitors, widely used for clathrin-mediated endocytosis, such as SCR [16][17][18][19][20][21] and CPZ [22][23][24][25] .…”

Section: Clathrin Is Required For Pixv and Rnv Entry Into Vero Cellsmentioning

confidence: 99%

“…Agents that disrupt clathrindependent receptor-mediated endocytosis such as Sucrose (SCR) and Chlorpromazine (CPZ) were used. SCR was necessary to generate a hypertonic medium to disturb the formation of clathrin vesicles on the cell membrane [16][17][18][19][20][21] . CPZ was used as it prevents clathrin-coated pit formation on the plasma membrane by promoting clathrin lattice assembly on endosomal membrane [22][23][24][25] .…”

Section: Introductionmentioning

confidence: 99%

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Members of Venezuelan Equine Encephalitis Complex entry into host cells by clathrin-mediated endocytosis in a pH-dependent manner

Ghietto

Gil

Quinteros

et al. 2022

Preprint

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Alphaviruses are enveloped, positive-sense, single-stranded RNA viruses of the Togaviridae family that are transmitted by arthropods and are important re-emerging agents that cause diseases in animals, as well as contagious human infections. Pixuna virus (PIXV) and Río Negro virus (RNV) are alphaviruses belonging to the Venezuelan Equine Encephalitis (VEE) complex, and are responsible for life-threatening diseases in equines. Considering that the first steps in viral infection are crucial for the efficient production of new progeny, the aim of this study was to elucidate early events of the replication cycle of these two viruses. To this end, we used chemical inhibitors and the expression of dominant-negative constructs to study the dependence of clathrin and endosomal pH on PIXV and RNV internalization mechanism. We demonstrated that both viruses are internalized primarily via clathrin-mediated endocytosis, where the low pH of endosomes is crucial for viral replication. Contributing knowledge the entry route of VEE complex members is important to understand the pathogenesis of these viruses and to develop new antiviral strategies.

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Ca²⁺‐dependent down‐regulation of human histamine H₁receptors in Chinese hamster ovary cells

Abstract: G q/11 protein-coupled human histamine H 1 receptors in Chinese hamster ovary cells stimulated with histamine undergo clathrin-dependent endocytosis followed by proteasome/lysosome-mediated down-regulation. In this study, we evaluated the effects of a sustained increase in intracellular Ca

Cited by 5 publications

References 45 publications

The microRNA‐204‐5p inhibits APJ signalling and confers resistance to cardiac hypertrophy and dysfunction

The microRNA‐204‐5p inhibits APJ signalling and confers resistance to cardiac hypertrophy and dysfunction

Differential Regulation of Thermodynamic Binding Forces of Levocetirizine and (S)-Cetirizine by Lys191 in Human Histamine H1 Receptors

Members of Venezuelan Equine Encephalitis Complex entry into host cells by clathrin-mediated endocytosis in a pH-dependent manner

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Ca2+‐dependent down‐regulation of human histamine H1receptors in Chinese hamster ovary cells

Cited by 5 publications

References 45 publications

The microRNA‐204‐5p inhibits APJ signalling and confers resistance to cardiac hypertrophy and dysfunction

The microRNA‐204‐5p inhibits APJ signalling and confers resistance to cardiac hypertrophy and dysfunction

Differential Regulation of Thermodynamic Binding Forces of Levocetirizine and (S)-Cetirizine by Lys191 in Human Histamine H1 Receptors

Members of Venezuelan Equine Encephalitis Complex entry into host cells by clathrin-mediated endocytosis in a pH-dependent manner

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Ca²⁺‐dependent down‐regulation of human histamine H₁receptors in Chinese hamster ovary cells