Abstract:
:Cystic fibrosis (CF) is an autosomal recessive disorder associated with mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene and defective chloride transport across the epithelial cell membranes. Abnormal epithelial ion transport is the primary cause of persistent airway infections and chronic inflammation in CF patients. In order to gain further insight into the mechanisms of epithelial dysfunctions linked to CFTR mutations, we performed and integrated proteomic and ionomic analysis of human bronchial epithelial IB3-1 cells and compared them with a CFTR-complemented isogenic cell line (C38). Aside from changes that were consistent with known effects related to CFTR mutations, such as differences in glycolytic and gluconeogenic pathways and unfolded protein responses, differential proteomics highlighted significant alteration of protein expression and, in particular, of the 14-3-3 signalling pathway that is known to be involved in cellular calcium (Ca) homeostasis. Of note, restoring chloride efflux by acting on Ca cellular homeostasis has been shown to be a promising therapeutic intervention for CF. Ionomic analysis showed significant changes in the IB3-1 element profile compared with C38 cells and in particular we observed an increase of intracellular Ca that significantly correlates with intracellular zinc (Zn) levels, suggesting a synergistic role of Ca and Zn influx. This finding is particularly intriguing because Zn has been reported to be effective in CF treatment increasing Ca influx. Taken together, our proteomic and ionomic data reveal that CFTR mutation sets in motion endogenous mechanisms counteracting impaired chloride transport mainly acting on epithelial ion transport and increasing intracellular Ca, suggesting potential links between protein expression and this response.
journal_name
Mol Biosystjournal_title
Molecular bioSystemsauthors
Ciavardelli D,D'Orazio M,Pieroni L,Consalvo A,Rossi C,Sacchetta P,Di Ilio C,Battistoni A,Urbani Adoi
10.1039/c3mb25594hsubject
Has Abstractpub_date
2013-06-01 00:00:00pages
1117-26issue
6eissn
1742-206Xissn
1742-2051journal_volume
9pub_type
杂志文章abstract::Transient and low-affinity interactions among macromolecules underlie many physiological events. Often, these interactions are difficult to study because they are not maintained when the participating molecules are removed from their cellular context. To circumvent this challenge, crosslinking reagents can be used to ...
journal_title:Molecular bioSystems
pub_type: 杂志文章,评审
doi:10.1039/b803218a
更新日期:2008-06-01 00:00:00
abstract::Abundant information about the nucleotide sequence of the human genome has become readily available and it is now necessary to develop methods for the identification of genes that are involved in important cellular, developmental and disease-related processes. Identification methods based on the activities of hammerhe...
journal_title:Molecular bioSystems
pub_type: 杂志文章,评审
doi:10.1039/b503235k
更新日期:2005-05-01 00:00:00
abstract::The biological processing - mechanism of cellular uptake, effects on the cytoplasmic and mitochondrial membranes, intracellular sites of localisation and induction of reactive oxygen species - of two dinuclear polypyridylruthenium(ii) complexes has been examined in three eukaryotic cells lines. Flow cytometry was used...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c6mb00431h
更新日期:2016-10-20 00:00:00
abstract::Polyethylenimine (PEI, especially with M(w) of 25,000) has been known as an efficient gene carrier and a gold standard of gene transfection due to its high transfection efficiency (TE). However, high concomitant cytotoxicity limited the application of PEI. In this report, several cationic polymers derived from low mol...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c0mb00339e
更新日期:2011-04-01 00:00:00
abstract::Bacterial resistance to β-lactam antibiotics poses a serious threat to human health. Penicillin binding proteins (PBPs) and β-lactamases are involved in both antibacterial activity and mediation of β-lactam antibiotic resistance. The two major reasons for resistance to β-lactams include: (i) pathogenic bacteria expres...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c3mb70537d
更新日期:2014-04-01 00:00:00
abstract::To identify an agent with specific activity against human lens epithelial cells (HLECs), we confirmed the presence of glucocorticoid receptors (GRs) and GR-α genes and evaluated whether GRs have a relationship with the apoptotic process in cultured HLECs. We also determined whether the inhibitor RU486 could rescue the...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c1mb05045a
更新日期:2011-06-01 00:00:00
abstract::The transforming growth factor beta (TGF-β) signaling pathway plays myriad roles in development and disease. TGF-β isoforms initiate signaling by organizing their cell surface receptors TβRI and TβRII. Exploration and exploitation of the versatility of TGF-β signaling requires an enhanced understanding of structure-fu...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c0mb00115e
更新日期:2010-12-01 00:00:00
abstract::Proteomics is the study of proteins and their interactions within complex biological systems. While this field is often associated with mass spectrometry, it is more useful to consider proteomics in the context of an objective: to identify and understand the molecular basis of health and disease at the protein level i...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/b611446f
更新日期:2007-01-01 00:00:00
abstract::Structural insight into DNA quadruplex structures formed by oligodeoxyribonucleotides 3'TG5'-5'GGGT3' (QS55) and 5'TG3'-3'GGGT5' (QS33) is presented. NMR analysis reveals that QS33 forms a parallel-like four-fold symmetric quadruplex, while QS55 possesses a two-fold symmetry and is characterized by a tetrameric antipa...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/b718778e
更新日期:2008-05-01 00:00:00
abstract::Molecular docking methods were applied to simulate the coupling of a set of nineteen acyl homoserine lactone analogs into the binding site of the transcriptional receptor LasR. The best pose of each ligand was explored and a qualitative analysis of the possible interactions present in the complex was performed. From t...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c3mb70181f
更新日期:2014-05-01 00:00:00
abstract::Major progress in the study of RNase P has resulted from crystallography of bacterial catalytic subunits and the discovery of catalytic activity in eukaryotes. Several new substrates have also been identified, primarily in bacteria but also in yeast. Our current world should be called the "RNA-protein world" rather th...
journal_title:Molecular bioSystems
pub_type: 杂志文章,评审
doi:10.1039/b707850c
更新日期:2007-09-01 00:00:00
abstract::Human mitogen-activated protein kinase (MAPK) family members JNK and p38 are two homologous protein-serine/threonine kinases but play distinct roles in the pathological process of neurological disorders. Selective targeting of JNK over p38 has been established as a potential therapeutic approach to epilepsy and other ...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c6mb00297h
更新日期:2016-07-19 00:00:00
abstract::Protein tyrosine phosphatases are crucial regulators of signal transduction and function as antagonists towards protein tyrosine kinases to control reversible tyrosine phosphorylation, thereby regulating fundamental physiological processes. Growing evidence has supported the notion that reversible oxidative inactivati...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c5mb00847f
更新日期:2016-05-24 00:00:00
abstract::The importance of microRNA (miRNA) in modulating gene expression at the post-transcriptional level is well known. Such regulation has been shown to influence the dynamics of several regulatory networks including the cell cycle. In this study we incorporated regulatory effects of intronic miRNA into an existing mathema...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c2mb25046b
更新日期:2012-08-01 00:00:00
abstract::A liquid chromatography coupled with mass spectrometry (LC/MS) based metabonomics approach was applied to characterize the aging of rats, and the anti-aging effect of total flavones of Epimedium (TFE), a traditional Chinese medicine, has also been investigated. Serum samples collected from 4, 10, 18 and 24 month-old r...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/b816407j
更新日期:2009-10-01 00:00:00
abstract::J proteins are a diverse family of co-chaperones that cooperate with heat shock protein 70 (Hsp70) to coordinate protein quality control, especially in response to cellular stress. Current models suggest that individual J proteins might play roles in recruiting Hsp70s to specific functions, such as maintaining cell wa...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c2mb25248a
更新日期:2012-11-01 00:00:00
abstract::There are major issues regarding the proposed pathway for starch degradation in germinating cereal grain. Given the commercial importance but genetic intractability of the problem, we have embarked on a program of chemical genetics studies to identify and dissect the pathway and regulation of starch degradation in ger...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c0mb00204f
更新日期:2011-03-01 00:00:00
abstract::Diabetic retinopathy (DR) is a serious microvascular syndrome of diabetes, and is one of the most frequent causes of blindness in the world. It has three progressive stages with complex metabolic deregulations in the holistic system of Western medicine. Chinese medicine classifies DR into two different syndrome types;...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c0mb00341g
更新日期:2011-07-01 00:00:00
abstract::Within systems biology there is an increasing interest in the stochastic behavior of genetic and biochemical reaction networks. An appropriate stochastic description is provided by the chemical master equation, which represents a continuous time Markov chain (CTMC). In this paper we consider the stochastic properties ...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c1mb05086a
更新日期:2011-10-01 00:00:00
abstract::The emerging field of synthetic biology is generating insatiable demands for synthetic genes, which far exceed existing gene synthesis capabilities. This review discusses the current methods of chemical DNA synthesis and gene assembly, as well as the latest engineering tools, technologies and trends which could potent...
journal_title:Molecular bioSystems
pub_type: 杂志文章,评审
doi:10.1039/b822268c
更新日期:2009-07-01 00:00:00
abstract::Drug promiscuity is one of the key issues in current drug development. Many famous drugs have turned out to behave unexpectedly due to their propensity to bind to multiple targets. One of the primary reasons for this promiscuity is that drugs bind to multiple distinctive target environments, a feature that we call mul...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/b901356c
更新日期:2009-08-01 00:00:00
abstract::Structural and functional changes in albumin are of particular interest as numerous studies in vivo have reported a strong involvement of glycated-HSA in the development and progression of chronic diabetic complications. Non-enzymatic addition of glucose molecules to a protein induces structural changes in it. These c...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c6mb00324a
更新日期:2016-07-19 00:00:00
abstract::Induced reprogramming of somatic cells has had a great impact on stem cell research, and the reprogramming technologies have evolved from four transgenic factors (Oct4, Sox2, Klf4, and c-Myc; OSKM) to just a few microRNAs (mainly miR-290/302 seed family). Despite these advances, the molecular events occurring during v...
journal_title:Molecular bioSystems
pub_type: 杂志文章,评审
doi:10.1039/c2mb25088h
更新日期:2013-01-27 00:00:00
abstract::The pro-inflammatory cytokines interleukin 1 (IL-1) and 6 (IL-6) are crucially involved in the regulation of a multitude of physiological processes, in particular coordinating the immune response upon bacterial infection and tissue injury. Both interleukins induce complex signalling cascades and trigger the production...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c1mb05261f
更新日期:2011-12-01 00:00:00
abstract::In the post-genome era, one of the most important and challenging tasks is to identify the subcellular localizations of protein complexes, and further elucidate their functions in human health with applications to understand disease mechanisms, diagnosis and therapy. Although various experimental approaches have been ...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c3mb25451h
更新日期:2013-04-05 00:00:00
abstract::Glucocorticoids (GCs) have been proved to be an important pathogenic factor of some neuropsychiatric disorders. Usually, a classical injury model based on corticosterone-induced cytotoxicity of differentiated rat pheochromocytoma (PC12) cells was used to stimulate the state of GC damage of hippocampal neurons and inve...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c5mb00642b
更新日期:2016-03-01 00:00:00
abstract::Escherichia coli has evolved an intracellular pathway to regulate its motion termed as chemotaxis so as to move towards a favorable environment such as regions with higher concentration of nutrients. Chemotaxis is a response to temporal and spatial variation of extracellular ligand concentration and randomness in moti...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/b924368b
更新日期:2010-06-01 00:00:00
abstract::Low transfection efficiency and inactivation by serum are the major drawbacks for cationic polymers when used as non-viral gene vectors. Here, a series of N-succinyl-chitosan-graft-polyethylenimine (NSC-g-PEI) copolymers with different compositions were synthesized through grafting low molecular weight PEI (800 Da) to...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/b822505b
更新日期:2009-06-01 00:00:00
abstract::Naphthalene, a polycyclic aromatic hydrocarbon, is a ubiquitous environmental pollutant capable of causing illness. In this study, we deconvoluted the metabolites related to naphthalene intervention in various organs by using nuclear magnetic resonance (NMR) and liquid chromatography-tandem mass spectrometry (LC-MS/MS...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c4mb00090k
更新日期:2014-07-01 00:00:00
abstract::We recently reported a chemical genetic method for generating bivalent inhibitors of protein kinases. This method relies on the use of the DNA repair enzyme O(6)-alkylguanine-DNA alkyltransferase (AGT) to display an ATP-competitive inhibitor and a ligand that targets a secondary binding domain. With this method potent...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c0mb00108b
更新日期:2011-02-01 00:00:00