The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Chen Zhang - One of the best experts on this subject based on the ideXlab platform.
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influence of polymorphisms in genes slc1a1 grin2b and GRIK2 on clozapine induced obsessive compulsive symptoms
Psychopharmacology, 2013Co-Authors: Jun Cai, Wen Zhang, Jun Chen, Yiru Fang, Chen ZhangAbstract:Clinical observations indicate that atypical antipsychotics, especially clozapine, induce obsessive–compulsive (OC) symptoms in schizophrenia patients. Recent data from neuroimaging and clinical trials suggest a role for altered glutamate neurotransmission in the etiology of OC disorder (OCD), and SLC1A1, GRIN2B, and GRIK2 have all been reported to regulate glutamate transmission and affect OCD pathophysiology. This study aimed to determine whether SLC1A1, GRIN2B, and GRIK2 are associated with clozapine-induced OC symptoms. A total of 250 clinically stable schizophrenia patients receiving clozapine treatment were recruited. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was used to evaluate the severity of OC symptoms. Based on their Y-BOCS scores, 250 patients were divided into the OC and non-OC groups (patients with or without OC symptoms, respectively). Additionally, three reported OCD susceptibility polymorphisms, SLC1A1 (rs2228622), GRIN2B (rs890), and GRIK2 (rs1556995), were genotyped. Trends of association with OC symptoms were observed in rs2228622A and rs890T alleles. SLC1A1 and GRIN2B interaction was found in the significant two-locus gene–gene interaction model (p = 0.0021), using the multifactor dimensionality reduction method. Further analysis showed a significant interaction between SLC1A1 and GRIN2B on the Y-BOCS score (F 6, 137 = 7.650, p < 0.001), and individuals with AA/TT genotypes had a significantly higher mean Y-BOCS score than those with other genotypes, except AG/TT. These results suggest that SLC1A1, GRIN2B, and interactions between the two may potentially confer a susceptibility to OC symptoms in schizophrenia patients receiving clozapine.
Raghbir S Athwal - One of the best experts on this subject based on the ideXlab platform.
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senescence of normal human fibroblasts relates to the expression of ionotropic glutamate receptor glur6 GRIK2
Cancer Genomics & Proteomics, 2020Co-Authors: Vikramjit K Zhawar, Raj P Kandpal, Raghbir S AthwalAbstract:Background/aim Glutamate receptor GRIK2, previously designated as GluR6, is best described in neuronal cells. However, its biological relevance in non-neuronal cells is not well understood. We have investigated the expression of this important protein in normal human fibroblasts as a function of cell proliferation. Materials and methods We introduced expression constructs of all five isoforms (A-E) of GRIK2 in normal human fibroblasts and investigated the cells for the presence and localization of GRIK2, as well as for cell proliferation and senescence over a period of 24 days. Results The expression of GRIK2-A isoform led to immediate cessation of cell proliferation. However, the cell numbers increased by 1.5- to 9.0-fold in 24 days upon transfection with B, C, D and E isoforms, after which they entered a state of senescence. The decreased proliferation was reflected by incorporation of BrdU in only 2-8% of transfected cells even after culturing them for 16 days. Conclusion Our results are indicative of an association between GRIK2 and aging of fibroblasts.
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isoforms of ionotropic glutamate receptor GRIK2 induce senescence of carcinoma cells
Cancer Genomics & Proteomics, 2019Co-Authors: Vikramjit K Zhawar, Raj P Kandpal, Raghbir S AthwalAbstract:Background The aberrant regulation of growth and proliferation is a key feature of carcinoma cells. In order to use molecular strategies to correct these defects toward therapeutic purposes, it is important to characterize the entire spectrum of causative molecules. Materials and methods By using gene transfer technique, SKOV3 ovarian carcinoma cells were transduced with an expression construct of glutamate receptor 6 (glutamate ionotropic receptor kainate type subunit 2, GRIK2) in retroviral vector PQCXIP. The senescence of transduced cells was subsequently characterized. Results Our results demonstrated that retroviral transduction occurs with high frequency and transduced cells continue to proliferate, albeit at a significantly reduced rate, up to 39 days. Some transduced colonies stopped proliferating after 12 days, and none of the clones proliferated beyond 37 days. The doubling time for these transduced cells increased progressively until they reached a complete cell-cycle arrest. The proliferating cells were distinguished by bromodeoxyuridine incorporation and 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide assay. The growth and cell cycle arrest in transduced cells accompanied activation of senescence-associated β-galactosidase. Furthermore, we have demonstrated a decrease in the levels of active protein kinase B and increase in the abundance of inactive cyclin-dependent kinase 1. Conclusion These results indicate involvement of GRIK2 in senescence and suggests GRIK2 as a potential target for therapeutic intervention of cancer cells.
Yusun Chang - One of the best experts on this subject based on the ideXlab platform.
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glutamate receptor ionotropic kainate 2 silencing by dna hypermethylation possesses tumor suppressor function in gastric cancer
International Journal of Cancer, 2010Co-Authors: Chuen Hsueh, Yuwei Leu, Haoping Liu, Kwanghuei Lin, Tim H M Huang, Yusun ChangAbstract:Aberrant DNA methylation is considered a major mechanism for silencing tumor suppressor genes in gastric cancer. We used CpG microarray and differential methylation hybridization strategies to identify potential tumor suppressor genes and recovered glutamate receptor, ionotropic, kainate 2 (GRIK2) as a novel epigenetic target in gastric cancer. Additional experiments showed that the promoter region of GRIK2 was hypermethylated in 3 of the 4 tested gastric cancer cell lines, and its expression was restored by treatment of cells with the DNA methylation inhibitor, 5 0 -aza-dC. In clinical samples, the GRIK2 promoter was differentially hypermethylated in tumor tissues compared with adjacent normal tissues (p < 0.001), and this methylation was inversely correlated with the expression level of GRIK2 mRNA (r 52 0.44). Functional studies further showed that GRIK2-expressing gastric cancer cell lines showed decreased colony formation and cell migration. Taken together, these results suggest that GRIK2 may play a tumor-suppressor role in gastric cancer. Future studies are warranted to examine whether DNA hypermethylation of the GRIK2 promoter can be used as a potential tumor marker for gastric cancer.
Vikramjit K Zhawar - One of the best experts on this subject based on the ideXlab platform.
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senescence of normal human fibroblasts relates to the expression of ionotropic glutamate receptor glur6 GRIK2
Cancer Genomics & Proteomics, 2020Co-Authors: Vikramjit K Zhawar, Raj P Kandpal, Raghbir S AthwalAbstract:Background/aim Glutamate receptor GRIK2, previously designated as GluR6, is best described in neuronal cells. However, its biological relevance in non-neuronal cells is not well understood. We have investigated the expression of this important protein in normal human fibroblasts as a function of cell proliferation. Materials and methods We introduced expression constructs of all five isoforms (A-E) of GRIK2 in normal human fibroblasts and investigated the cells for the presence and localization of GRIK2, as well as for cell proliferation and senescence over a period of 24 days. Results The expression of GRIK2-A isoform led to immediate cessation of cell proliferation. However, the cell numbers increased by 1.5- to 9.0-fold in 24 days upon transfection with B, C, D and E isoforms, after which they entered a state of senescence. The decreased proliferation was reflected by incorporation of BrdU in only 2-8% of transfected cells even after culturing them for 16 days. Conclusion Our results are indicative of an association between GRIK2 and aging of fibroblasts.
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isoforms of ionotropic glutamate receptor GRIK2 induce senescence of carcinoma cells
Cancer Genomics & Proteomics, 2019Co-Authors: Vikramjit K Zhawar, Raj P Kandpal, Raghbir S AthwalAbstract:Background The aberrant regulation of growth and proliferation is a key feature of carcinoma cells. In order to use molecular strategies to correct these defects toward therapeutic purposes, it is important to characterize the entire spectrum of causative molecules. Materials and methods By using gene transfer technique, SKOV3 ovarian carcinoma cells were transduced with an expression construct of glutamate receptor 6 (glutamate ionotropic receptor kainate type subunit 2, GRIK2) in retroviral vector PQCXIP. The senescence of transduced cells was subsequently characterized. Results Our results demonstrated that retroviral transduction occurs with high frequency and transduced cells continue to proliferate, albeit at a significantly reduced rate, up to 39 days. Some transduced colonies stopped proliferating after 12 days, and none of the clones proliferated beyond 37 days. The doubling time for these transduced cells increased progressively until they reached a complete cell-cycle arrest. The proliferating cells were distinguished by bromodeoxyuridine incorporation and 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide assay. The growth and cell cycle arrest in transduced cells accompanied activation of senescence-associated β-galactosidase. Furthermore, we have demonstrated a decrease in the levels of active protein kinase B and increase in the abundance of inactive cyclin-dependent kinase 1. Conclusion These results indicate involvement of GRIK2 in senescence and suggests GRIK2 as a potential target for therapeutic intervention of cancer cells.
Chenping Zhang - One of the best experts on this subject based on the ideXlab platform.
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2653 influence of polymorphisms in genes slc1a1 grin2b and GRIK2 on clozapine induced obsessive compulsive symptoms
European Psychiatry, 2013Co-Authors: Chenping ZhangAbstract:Rationale Clinical observations indicate that atypical antipsychotics, especially clozapine, induce obsessive–compulsive (OC) symptoms in schizophrenia patients. Recent data from neuroimaging and clinical trials suggest a role for altered glutamate neurotransmission in the etiology of OC disorder (OCD), and SLC1A1, GRIN2B, and GRIK2 have all been reported to regulate glutamate transmission and affect OCD pathophysiology.
