Peptides extracted from common bean (Phaseolus vulgaris L.) non-digestible fraction caused differential gene expression of HCT116 and RKO human colorectal cancer cells
FOOD RESEARCH INTERNATIONAL
Authors: Luna Vital, Diego A.; Loarca-Pina, Guadalupe; Dia, Vermont P.; Gonzalez de Mejia, Elvira
Abstract
The role in cancer chemoprevention of proteins present in non-digestible fraction of common bean (Phaseolus vulgaris L.) is unknown. The aim was to examine the effect of peptide extracted from two cultivars of the common bean Azufrado Higuera (AH-PE) and Bayo Madero (BM-PE) on a gene expression using human colon cancer cells through a microarray analysis. HCT116 and RKO colon cancer cells were treated with 0.5 mg/mL AH-PE and BM-PE for 24 h; RNA was extracted and the gene expression was analyzed using an Agilent Low Input Quick Amp Labeling assay. In the HCT116 human cells, 511 and 964 genes were affected by the AH-PE and BM-PE treatments, respectively, with 405 genes found to be commonly affected by peptide extracts. In the RKO human cells, 45 and 32 genes were affected significantly by the AH-PE and BM-PE treatments, respectively, with 19 genes common for both extracts. Bioinformatic analysis using Database for Annotation Validation and Integrated Discovery showed that the primary genes affected were involved with oxidation reduction, response to stimulus, protein phosphatase, MAPK signaling, selenium binding and response to wounding. Ingenuity Pathway Analysis showed that in the HCT116 cell line, NRF-2 related antioxidant enzymes were up-regulated while glutathione redox-related enzymes were down-regulated in the RKO cell line, potentially causing reactive oxygen species (ROS) imbalance. Validation of genes by RT-PCR showed good agreement for the genes with a potential role in cancer proliferation and apoptosis (PDE4B and OSGIN1, and KRT19 and EEF1A2). This study discovered, for the first time, 8 differentially expressed genes to be similar for both human colon cancer cell lines triggered by both bean cultivars, namely C11orf31, C9orf169, EMP1, GEM, PLIN2, SUN3, TRIM16L and TXNRD1. (C) 2014 Elsevier Ltd. All rights reserved.
Association of VSNL1 with schizophrenia, frontal cortical function, and biological significance for its gene product as a modulator of cAMP levels and neuronal morphology
TRANSLATIONAL PSYCHIATRY
Authors: Braunewell, K. H.; Dwary, A. D.; Richter, F.; Trappe, K.; Zhao, C.; Giegling, I.; Schoenrath, K.; Rujescu, D.
Abstract
We report an association of single-nucleotide polymorphisms (SNPs) for the VSNL1 gene (visinin-like 1) with schizophrenia and frontal cortical function in a sample of patients with Diagnostic and Statistical Manual of Mental Disorder-IV (DSM-IV) diagnoses of schizophrenia, compared with healthy controls. Moreover, VSNL1 SNPs were associated with performance in the Wisconsin Card Sorting Test, a measure for the assessment of frontal cortical function. The VSNL1 gene product, Visinin-like-protein-1 (VILIP-1), is a member of the neuronal EF-hand Ca2+-sensor protein family. Previously, VILIP-1 mRNA and protein expression were shown to be altered in animal models and in schizophrenia patients. VILIP-1 influences cytosolic cyclic adenosine mono phosphate (cAMP) levels, cell migration, exocytotic processes and differentiation in the periphery. This raises the question, whether, similar to other potential schizophrenia susceptibility genes such as Disc1, PDE4B and Akt, VSNL1 may affect cAMP signaling and neurite outgrowth in neurons. In dissociated rat hippocampal neurons, VILIP-1 small interfering RNA knockdown decreased cAMP levels and reduced dendrite branching, compared with control-transfected cells. In contrast, VILIP-1 overexpression had the opposite effect. Similar results have been obtained in the human dopaminergic neuronal cell line SH-SY5Y, where the effect on neurite branching and length was attenuated by the adenylyl cyclase inhibitor 2',5'-dideoxyadenosine and the protein kinase A inhibitor KT5720. These results show that the association of VSNL1 SNPs with the disease and cognitive impairments, together with previously observed pathological changes in VILIP-1 protein expression, possibly occurring during brain development, may contribute to the morphological and functional deficits observed in schizophrenia.