Molecular mechanisms involved in epidermal growth factor receptor-mediated inhibition of dopamine D₃ receptor signaling

Sun, Ningning,Zhang, Xiaowei,Guo, Shuohan,Le, Hang Thi,Zhang, Xiaohan,Kim, Kyeong-Man Elsevier 2018 Biochimica et biophysica acta, Molecular cell rese Vol.1865 No.9

<P><B>Abstract</B></P> <P>The phenomenon wherein the signaling by a given receptor is regulated by a different class of receptors is termed transactivation or crosstalk. Crosstalk between receptor tyrosine kinases (RTKs) and G protein-coupled receptors (GPCRs) is highly diverse and has unique functional implications because of the distinct structural features of the receptors and the signaling pathways involved. The present study used the epidermal growth factor receptor (EGFR) and dopamine D<SUB>3</SUB> receptor (D<SUB>3</SUB>R), which are both associated with schizophrenia, as the model system to study crosstalk between RTKs and GPCRs. Loss-of-function approaches were used to identify the cellular components involved in the tyrosine phosphorylation of G protein-coupled receptor kinase 2 (GRK2), which is responsible for EGFR-induced regulation of the functions of D<SUB>3</SUB>R. <I>SRC</I> proto-oncogene (Src, non-receptor tyrosine kinase), heterotrimeric G protein Gβγ subunit, and endocytosis of EGFR were involved in the tyrosine phosphorylation of GRK2. In response to EGF treatment, Src interacted with EGFR in a Gβγ-dependent manner, resulting in the endocytosis of EGFR. Internalized EGFR in the cytosol mediated Src/Gβγ-dependent tyrosine phosphorylation of GRK2. The binding of tyrosine-phosphorylated GRK2 to the T142 residue of D<SUB>3</SUB>R resulted in uncoupling from G proteins, endocytosis, and lysosomal downregulation. This study identified the molecular mechanisms involved in the EGFR-mediated regulation of the functions of D<SUB>3</SUB>R, which can be extended to the crosstalk between other RTKs and GPCRs.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Stimulation of EGFR results in the tyrosine phosphorylation of GRK2. </LI> <LI> Gβγ, Src, and endocytosis of EGFR are required for the tyrosine phosphorylation of GRK2. </LI> <LI> Tyrosine phosphorylated GRK2 binds to T142 of D<SUB>3</SUB>R. </LI> <LI> GRK2-bound D<SUB>3</SUB>R is uncoupled from G proteins to result in signaling inhibition. </LI> <LI> GRK2-bound D<SUB>3</SUB>R undergoes endocytosis and degradation through lysosomal pathway. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

TRIM22 promotes the proliferation of glioblastoma cells by activating MAPK signaling and accelerating the degradation of Raf-1

Fei Xiaowei,Dou Ya-nan,Sun Kai,Wei Jialiang,Guo Qingdong,Wang Li,Wu Xiuquan,Lv Weihao,Jiang Xiaofan,Fei Zhou 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

The tripartite motif (TRIM) 22 and mitogen-activated protein kinase (MAPK) signaling pathways play critical roles in the growth of glioblastoma (GBM). However, the molecular mechanism underlying the relationship between TRIM22 and MAPK signaling remains unclear. Here, we found that TRIM22 binds to exon 2 of the sphingosine kinase 2 (SPHK2) gene. An ERK1/2-driven luciferase reporter construct identified TRIM22 as a potential activator of MAPK signaling. Knockout and overexpression of TRIM22 regulate the inhibition and activation of MAPK signaling through the RING-finger domain. TRIM22 binds to Raf-1, a negative regulator of MAPK signaling, and accelerates its degradation by inducing K48-linked ubiquitination, which is related to the CC and SPRY domains of TRIM22 and the C1D domain of Raf-1. In vitro and in vivo, an SPHK2 inhibitor (K145), an ERK1/2 inhibitor (selumetinib), and the nonphosphorylated mutant Raf-1S338A inhibited GBM growth. In addition, deletion of the RING domain and the nuclear localization sequence of TRIM22 significantly inhibited TRIM22-induced proliferation of GBM cells in vivo and in vitro. In conclusion, our study showed that TRIM22 regulates SPHK2 transcription and activates MAPK signaling through posttranslational modification of two critical regulators of MAPK signaling in GBM cells.

Physical, Chemical Properties and Structural Changes of Zaodan Pickled by Vacuum Decompression Technology

Naxin Sun,Huiping Liu,Xiaowei Zhang,Hongni Wang,Shaojuan Liu,Pei Chen,Weijie Yu,Kai Liu 한국축산식품학회 2018 한국축산식품학회지 Vol.38 No.2

To shorten the production cycle of Zaodan, this study first pickled Zaodan by a novel technology -vacuum decompression technology. Vacuum decompression technology could reduce the pickling time of Zaodan from 20wkto about 9wk.The protein content, moisture and pH of the Zaodan egg white gradually decreased with a concomitant increase in salt during the pickling process. The total sulfhydryl group (SH) group content of the egg white proteins was increased to 2.43×10-3mol/L after being pickled for 30 d, whereas the content of disulphide bonds (SS) was reduced to 23.35×10-3mol/L. The surface hydrophobicity was lowest after pickling for 30 d. In addition, great changes occurred in the secondary structure of the egg white proteins after pickling for 20 d. The disappearance of ovomucin was noticeable based on sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis.

Identification and Evaluation of Cytotoxicity of Peptide Liposome Incorporated Citron Extracts in an in Vitro System

Zhang, Xiaowei,Yoon, Hee Jeong,Kang, Min Gyeong,Kim, Gyeong Jin,Shin, Sun Young,Baek, Sang Hong,Lee, Jung Gyu,Bai, Jingjing,Lee, Sang Yoon,Choi, Mi Jung,Hong, Kwonho,Bae, Hojae MDPI 2018 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.19 No.2

<P>Citrons have been widely used for medicinal purposes for a long time, but the application of citron in the food industry is still restricted. The extensive advantages of nanotechnology in the food industry have greatly broadened the application of foods. In this study, by employing nanotechnology, we prepared citron-extract nanoparticle with an average size of 174.11 ± 3.89 nm, containing protein peptide and/or liposome. In order to evaluate the toxicity of nanoparticles and to ensure food safety, biological cytotoxicity at the cell and genomic levels was also identified to examine the toxicity of citron extracts by using an in vitro system. Our results demonstrated that the cytotoxicity of citron<SUB>liposome</SUB> was dependent on cell type in high concentrations (1 and 5 mg/mL), selectively against primary human cardiac progenitor cells (hCPCs), and human endothelial progenitor cells (hEPCs) in MTT and lactate dehydrogenase (LDH) assays. Interestingly, for the NIH-3T3 and H9C2 cell lines, cell cytotoxicity was observed with slight genotoxicity, especially from citron<SUB>peptide</SUB> extract for both cell lines. Taken together, our study provides cytotoxicity data on nanoengineered citron extracts according to different cell type as is crucial for further applications.</P>

Experimental Study on Hydraulic Erosion Characteristics of Ecological Slope of Tailings Reservoir under Rainfall

Yang Sun,Xiaowei Gu,Xiaochuan Xu 대한토목학회 2021 KSCE JOURNAL OF CIVIL ENGINEERING Vol.25 No.7

Rainfall infiltration is the main factor of hydraulic erosion and deformation instability of tailings reservoir slope. Through the hydraulic erosion test of tailings reservoir slope based on rainfall, the parameters of slope internal moisture content, runoff sediment concentration, runoff, start time of surface erosion and gully erosion and slope velocity were tested. The slope protection effect of ecological base material of tailings reservoir slope determined in the previous study was evaluated. The results show that the vegetation allocation model combined with grass, shrub and flower is effective in hydraulic erosion protection of tailings reservoir slope. The critical slope range of ecological slope model of tailings reservoir is 37.5° − 42.3° under three kinds of rain intensity. The research results can provide certain theoretical and technical support for the safe operation of tailings reservoir and the development of ecological slope protection theory of tailings reservoir.

Ionization and Electrical Conductivity of Dense Carbon

Zhijian Fu,Xiaowei Sun,Weilong Quan 한국물리학회 2013 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.62 No.3

The electrical conductivity of a dense carbon plasma has been calculated by using a linear mixture rule considering various interactions among electrons, atoms, and ions in the density and temperature ranges of 10⁻⁵ - 10 g cm⁻³ and 10⁴ - 10⁵ K, respectively. The non-ideal Saha equation is used to obtain the plasma composition and the degree of ionization successfully. The present calculation spans from the weakly coupled, nondegenerate region to the strong coupled, degenerate domain. The calculated conductivity is in reasonable agreement with the explosive wire measurement and the quantum kinetic calculation. A nonmetal-metal transition is predicted to occur at 0.56 g cm⁻³ at temperatures lower than 3 × 10⁴ K based on the calculation of the electrical conductivity.

Architectural Characteristics and Optimization of Canopy Microclimate in High-Trunk, Open Center Trees of ‘Fuji’ Apple

Qinping Wei,Xiaowei Wang,Lujun,Zihong Sun,Zhu Liqin 한국원예학회 2006 한국원예학회 기타간행물 Vol.- No.-

Kinetics and mechanism study of H-acid degradation by peroxymonosulfate activation with Co3O4-Fe2O3/Al2O3

Ping Dai,Xiaowei Sun,Dongyan Xu,Feng Tan 한국화학공학회 2020 Korean Journal of Chemical Engineering Vol.37 No.6

Alumina supported bimetallic cobalt-iron oxide (Co3O4-Fe2O3/Al2O3) catalyst was prepared via co-impregnation of boehmite with the mixture solution of cobalt nitrate and iron nitrate followed by calcination in air. X-ray photoelectron spectroscopy and high-resolution transmission electron microscope analyses confirmed the existence of highly dispersed Co3O4 and Fe2O3 nanoparticles in the as-prepared catalysts. The catalytic activity of Co3O4-Fe2O3/Al2O3 was evaluated for the degradation of H-acid in aqueous solution by heterogeneous activation of peroxymonosulfate. The results indicated that the Co3O4-Fe2O3/Al2O3 catalyst exhibited an identical initial activity but much better recyclability than Co3O4/Al2O3 due to its low amount of metal leaching and possible redox circle of Co(II)/Co(III). Electron paramagnetic resonance spectroscopy and radical quenching experiments suggested that singlet oxygen (1O2) contributed much more than ·OH and SO4 • to H-acid degradation, and the degradation mainly followed a nonradical reaction mechanism.

Molecular Cloning, mRNA Expression, and Localization of the G-protein Subunit Galphaq in Sheep Testis and Epididymis

Li, Zhen,Lu, Jieli,Sun, Xiaowei,Pang, Quanhai,Zhao, Yiwen Asian Australasian Association of Animal Productio 2016 Animal Bioscience Vol.29 No.12

The reproductive function of G-protein subunit Galphaq (GNAQ), a member of the G protein alpha subunit family, has been extensively studied in humans and rats. However, no data is available on its status in ruminants. The objectives of this study were to evaluate the expression pattern of the GNAQ in the testis and epididymis of sheep by polymerase chain reaction (PCR). The mRNA expression levels were detected by real-time fluorescent quantitative PCR, and cellular localization of GNAQ in the testis and epididymis was examined by immunohistochemistry. Additionally, GNAQ protein was qualitatively evaluated via western blot, with the results indicating that similarities between GNAQ mRNA levels from sheep was highly conserved with those observed in Bos taurus and Sus scrofa. Our results also indicated that GNAQ exists in the caput and cauda epididymis of sheep, while GNAQ in the testis and epididymis was localized to Leydig cells, spermatogonial stem cells, spermatocytes, Sertoli cells, spermatid, principal cells, and epididymis interstitial cells. The concentrations of GNAQ mRNA and protein in the caput and cauda epididymis were significantly greater than those observed in the corpus epididymis (p<0.01) and testis (p<0.05). Our results indicated that GNAQ exists at high concentrations in the caput and cauda epididymis of sheep, suggesting that GNAQ may play an important role in gonad development and sperm maturation.

Electrochemistry and Leaching Kinetics of Gold-Silver Alloys in Cyanide Solutions

Guan, Y.Charles,Sun, Xiaowei,Han, Kenneth N. The Korean Institute of Resources Recycling 2001 資源 리싸이클링 Vol.10 No.1

The dissolution behavior of gold and silver from gold-silver alloys in aerated cyanide solutions has been investigated by an electrochemical means as well as a direct measurement of gold and silver ions reported in the bulk solution as a function of time using rotating disc electrodes. The variables studied included oxygen partial pressure, rotating speed of the disc, concentration of cyanide, temperature and composition of the allyos. The dissolution potential and the rate of dissolution were obtained in view of the anodic and cathodic current-potential relationships. The results were discussed in terms of the mixed potential theory. The results showed that the dissolution rate of gold and silver from the alloys was controlled partially by chemical reaction. but largely by transport of either oxygen or cyanide, depending on their relative concentration under the experimental conditions employed in this study.