Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 6 de 6
Mais filtros

Base de dados
Intervalo de ano de publicação
J Membr Biol ; 253(1): 43-55, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31820013


Lysophosphatidylcholine (LPC) is a major atherogenic lipid that stimulates an increase in mitochondrial reactive oxygen species (mtROS) and the release of cytokines under inflammasome activation. However, the potential receptors of LPC in macrophages are poorly understood. Members of the transient receptor potential (TRP) channel superfamily, which is crucially involved in transducing environmental irritant stimuli into nociceptor activity, are potential receptors of LPC. In this study, we investigated whether LPC can induce the activation of transient receptor potential ankyrin 1 (TRPA1), a member of the TRP superfamily. The functional expression of TRPA1 was first detected by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting and calcium imaging in human acute monocytic leukemia cell line (THP-1)-derived macrophages. The mechanism by which LPC induces the activation of macrophages through TRPA1 was verified by cytoplasmic and mitochondrial calcium imaging, mtROS detection, a JC-1 assay, enzyme-linked immunosorbent assay, the CCK-8 assay and the lactate dehydrogenase (LDH) cytotoxic assay. LPC induced the activation of THP-1-derived macrophages via calcium influx, and this activation was suppressed by potent and selective inhibitors of TRPA1. These results indicated that TRPA1 can mediate mtROS generation, mitochondrial membrane depolarization, the secretion of IL-1ß and cytotoxicity through cellular and mitochondrial Ca2+ influx in LPC-treated THP-1-derived macrophages. Therefore, the inhibition of TRPA1 may protect THP-1-derived macrophages against LPC-induced injury.

Genes Brain Behav ; : e12625, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31730264


Temperature sensing is an important adaptive mechanism for warm-blooded animals such as humans. ThermoTRP ion channels are activated by distinct but overlapping physiological temperatures. Our previous research demonstrated that sorting nexin 11 (SNX11) regulates lysosomal degradation of plasma membrane TRPV3, one of ThermoTRP ion channel proteins. Here, we found that SNX11, a vesicular trafficking protein, modulates mouse behaviour in response to temperature changes. Snx11-knockout mice exhibit a stronger preference for mild temperatures along with enhanced sensitivity to harmful heat. Mechanistically, keratinocytes from Snx11-knockout mice exhibit a larger temperature-gated TRPV3 membrane current and have enhanced thermoTRPV3 expression in the plasma membrane compared to wild-type keratinocytes. Additionally, Snx11-knockout mice show higher endogenous TRPV3 protein levels in skin tissues than wild-type mice do. Therefore, our results indicate that SNX11 may regulate thermal perception via alteration of functional thermoTRPV3 on the plasma membrane of thermally sensitive cells, which is the first link between vesicular trafficking and thermal transduction.

Stem Cell Res ; 40: 101571, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31520889


Autism spectrum disorder (ASD) is a neurological disorder with complex etiologies. In this study, urine cells were collected from a 16-year-old male with ASD and reprogrammed with the human SKOM transcription factors. The patient has a heterozygous C > T mutation of FCGR1B gene that was confirmed by sequencing analysis. The pluripotency was verified by gene expression and capacity of differentiation towards the three germ layers. This kind of iPSC will be valuable for further understanding the pathogenesis of ASD and help to develop drugs for treating ASD.

J Nanosci Nanotechnol ; 19(9): 5435-5440, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30961693


Vitamin D plays a major role in the regulation of calcium homeostasis and affects bone metabolism. There is currently limited detailed knowledge about the vitamin D endocrine system in human bone cells. Here, we investigated the direct effects of 1α, 25-dihydroxyvitamin D3 (1α, 25-(OH)2D3 or 'VD3') on osteogenesis of human umbilical cord mesenchymal stem cells (HUCMSCs). We also studied the impact of VD3 on intracellular Ca2+ concentrations in osteogenic cells. The results of alizarin red staining and alkaline phosphatase activity tests showed that VD3 could not induce osteogenic differentiation in HUCMSCs. However, addition of VD3 to the osteogenic differentiationinducing medium could promote HUCMSC to differentiate into osteoblasts. Calcium imaging showed that the addition of VD3 increased intracellular Ca2+ concentrations in osteogenic HUCMSCs. Thus, we concluded that adding VD3 increased intracellular Ca2+ concentrations in osteogenic HUCMSCs and promoted their osteogenesis.

FEBS Open Bio ; 9(2): 206-225, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30761248


Some members of the transient receptor potential vanilloid (TRPV) subfamily of cation channels are thermosensitive. Earlier studies have revealed the distribution and functions of these thermo-TRPVs (TRPV1-4) in various organs, but their expression and function in the human esophagus are not fully understood. Here, we probed for the expression of the thermo-TRPVs in one nontumor human esophageal squamous cell line and two esophageal squamous cell carcinoma (ESCC) cell lines. TRPV1, TRPV2, and TRPV4 proteins were found to be upregulated in ESCC cells, while TRPV3 was not detectable in any of these cell lines. Subsequently, channel function was evaluated via monitoring of Ca2+ transients by Ca2+ imaging and nonselective cation channel currents were recorded by whole-cell patch clamp. We found that TRPV4 was activated by heat at 28 °C-35 °C, whereas TRPV1 and TRPV2 were activated by higher, noxious temperatures (44 °C and 53 °C, respectively). Furthermore, TRPV1 was activated by capsaicin (EC 50 = 20.32 µm), and this effect was antagonized by AMG9810; TRPV2 was activated by a newly developed cannabinoid compound, O1821, and inhibited by tranilast. In addition, TRPV4 was activated by hypotonic solutions (220 m Osm), and this effect was abolished by ruthenium red. The effects of TRPV1 and TRPV4 on ESCC were also explored. Our data, for the first time, showed that the overactivation of TRPV1 and TRPV4 promoted the proliferation and/or migration of ESCC cells. In summary, TRPV1, TRPV2, and TRPV4 were functionally expressed in human esophageal squamous cells, and thermo-TRPVs might play an important role in the development of ESCC.

Free Radic Biol Med ; 89: 1003-13, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26456053


Oxidative stress is important for the initiation and progression of cancers, which confers the cells with a survival advantage by inducing oxidative adaption and drug resistance. Therefore, developing strategies to promote oxidative stress-induced cytotoxicity could be important for cancer therapy. Herein, we found that H2O2-mediated oxidative stress increases TRPV2 expression in human hepatoma (HepG2 and Huh-7) cells. This occurred at the mRNA and protein levels in a dose-dependent manner. The significance of TRPV2 in promoting H2O2-induced cell death was demonstrated in gain and loss of function studies with overexpression and knockdown of TRPV2, respectively. Mechanistically, H2O2-induced cell death involves inhibition of pro-survival signaling proteins (Akt, Nrf2) and activation of pro-death signaling proteins (p38, JNK1). Overexpression of TRPV2 in H2O2-treated hepatoma cells aggravates the inhibition of Akt and Nrf2, while it enhances the activation of p38 and JNK1 at the early stage of cell death. Interestingly, increased expression of TRPV2 in HepG2 cells improved the efficacy of stress-associated chemicals to induce cell death. Our findings suggest that TRPV2 acts as an important enhancer for H2O2-induced cytotoxicity. This process occurred by the inhibition of Akt and Nrf2 as well as the early activation of p38 and JNK1. These findings have important implications for inhibition of oxidative adaption and drug resistance.

Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Peróxido de Hidrogênio/farmacologia , Neoplasias Hepáticas/patologia , Oxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Canais de Cátion TRPV/metabolismo , Western Blotting , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Proliferação de Células/efeitos dos fármacos , Citometria de Fluxo , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Canais de Cátion TRPV/genética , Células Tumorais Cultivadas , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo