共查询到20条相似文献,搜索用时 31 毫秒
1.
Vijay K. Singh Stephen Y. Wise Jessica R. Scott Patricia L.P. Romaine Victoria L. Newman Oluseyi O. Fatanmi 《Life sciences》2014
Aims
The objectives of this study were to determine the cytokine induction by delta tocotrienol (DT3, a promising radiation countermeasure) and to investigate the role of granulocyte colony-stimulating factor (G-CSF) in its radioprotective efficacy against ionizing radiation in mice.Main methods
Multiplex Luminex was used to analyze cytokines induced by DT3 and other tocols (gamma-tocotrienol and tocopherol succinate) in CD2F1 mice. Mice were injected with an optimal dose of DT3 and a G-CSF antibody, and their 30-day survival against cobalt-60 gamma-irradiation was monitored. The neutralization of G-CSF by the administration of a G-CSF-specific antibody in DT3-injected mice was investigated by multiplex Luminex.Key findings
Our data demonstrate that DT3 induced high levels of various cytokines comparable to other tocols being developed as radiation countermeasures. DT3 significantly protected mice against ionizing radiation, and the administration of a G-CSF neutralizing antibody to DT3-treated animals resulted in the complete abrogation of DT3's radioprotective efficacy and neutralization of G-CSF in peripheral blood.Significance
Our study findings suggest that G-CSF induced by DT3 mediates its radioprotective efficacy against ionizing radiation in mice. 相似文献2.
Zohreh Firouzi Parisa Lari Marzieh Rashedinia Mohammad Ramezani Mehrdad Iranshahi Khalil Abnous 《Life sciences》2014
Aims
Curcumin is one of the most important constituent of Curcuma longa L. with antioxidant, anti-inflammatory and anticancer effects. In this study, we investigated potential intracellular targets of curcumin by affinity chromatography based on target deconvolution. Identification of curcumin interacting proteins may help in evaluating biological and side effects of this natural compound.Main methods
Curcumin was immobilized through a linker to sepharose beads as solid matrix. Pull down assay was performed by passing tissue lysate of mouse brain through the column to enrich and purify curcumin interacting proteins. Then proteins were separated using two-dimensional gel electrophoresis and identified using MALDI/TOF/TOF mass spectrometry.Key findings
Our results show that curcumin physically binds to a wide range of cellular proteins including structural proteins, metabolic enzymes and proteins involved in apoptosis pathway.Significance
Finding curcumin interacting proteins may help in understanding a part of curcumin pharmacological effects. 相似文献3.
Aims
Melatonin possesses various pharmacological effects including neuroprotective effects against brain ischemia. Post-ischemic increases in matrix metalloproteinase-9 (MMP-9) expression and activity mainly contribute to neuronal damage by degradation of the extracellular matrix. This study was designed to examine whether melatonin has a neuroprotective effect and an influence on MMP-9 in transient global brain ischemia.Main methods
Mice were subjected to 20 min of global brain ischemia and sacrificed 72 h later. Melatonin (30 mg/kg) was administered 30 min before and 2 h after ischemia as well as once daily until sacrifice.Key findings
Hippocampal pyramidal cell damage after ischemia was significantly decreased by melatonin. As observed by zymography, melatonin inhibited the increase of MMP-9 activity after ischemia. In the brain sections, the increased gelatinase activity was mainly observed in the hippocampus after ischemia and melatonin also reduced gelatinase activity. The laminin and NeuN expression levels were reduced in the hippocampal CA1 and CA2 regions after ischemia, and melatonin reduced laminin degradation and neuronal loss. A TUNEL assay demonstrated that there were TUNEL-positive cells in the hippocampus and the number of TUNEL-positive cells was significantly decreased by melatonin. There was no difference in the ischemia-induced hippocampal neuronal damage between the vehicle- and melatonin-treated groups of MMP-9 knock-out mice.Significance
These data demonstrate that melatonin suppressed the occurrence of neuronal injury, which might be partly due to its inhibitory effects on MMP-9 in addition to its anti-oxidative effects. MMP-9 may be an important key target of melatonin in neuroprotection against global ischemia. 相似文献4.
Lukáš Kubala Hana Kolářová Jan Víteček Silvie Kremserová Anna Klinke Denise Lau Anna L.P. Chapman Stephan Baldus Jason P. Eiserich 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
Myeloperoxidase (MPO) is an abundant hemoprotein expressed by neutrophil granulocytes that is recognized to play an important role in the development of vascular diseases. Upon degranulation from circulating neutrophil granulocytes, MPO binds to the surface of endothelial cells in an electrostatic-dependent manner and undergoes transcytotic migration to the underlying extracellular matrix (ECM). However, the mechanisms governing the binding of MPO to subendothelial ECM proteins, and whether this binding modulates its enzymatic functions are not well understood.Methods
We investigated MPO binding to ECM derived from aortic endothelial cells, aortic smooth muscle cells, and fibroblasts, and to purified ECM proteins, and the modulation of these associations by glycosaminoglycans. The oxidizing and chlorinating potential of MPO upon binding to ECM proteins was tested.Results
MPO binds to the ECM proteins collagen IV and fibronectin, and this association is enhanced by the pre-incubation of these proteins with glycosaminoglycans. Correspondingly, an excess of glycosaminoglycans in solution during incubation inhibits the binding of MPO to collagen IV and fibronectin. These observations were confirmed with cell-derived ECM. The oxidizing and chlorinating potential of MPO was preserved upon binding to collagen IV and fibronectin; even the potentiation of MPO activity in the presence of collagen IV and fibronectin was observed.Conclusions
Collectively, the data reveal that MPO binds to ECM proteins on the basis of electrostatic interactions, and MPO chlorinating and oxidizing activity is potentiated upon association with these proteins.General significance
Our findings provide new insights into the molecular mechanisms underlying the interaction of MPO with ECM proteins. 相似文献5.
Wooyoung Jang Hee Ju Kim Huan Li Kwang Deog Jo Moon Kyu Lee Sun Hong Song Hyun Ok Yang 《Biochemical and biophysical research communications》2014
Background and objectives
Dysregulation of the autophagy pathway has been suggested as an important mechanism in the pathogenesis of Parkinson’s disease (PD). Therefore, modulation of autophagy may be a novel strategy for the treatment of PD. Recently, an active form of vitamin D3 has been reported to have neuroprotective properties. Therefore, we investigated the protective, autophagy-modulating effects of 1,25-dyhydroxyvitamin D3 (calcitriol) in an in vitro model of Parkinson’s disease.Methods
An in vitro model of Parkinson’s disease, the rotenone-induced neurotoxicity model in SH-SY5Y cells was adapted. We measured cell viability using an MTT assay, Annexin V/propidium iodide assay, and intracellular reactive oxygen species levels and analyzed autophagy-associated intracellular signaling proteins by Western blotting.Results
Rotenone treatment of SH-SY5Y cells reduced their viability. This treatment also increased reactive oxygen species levels and decreased levels of intracellular signaling proteins associated with cell survival; simultaneous exposure to calcitriol significantly reversed these effects. Additionally, calcitriol increased levels of autophagy markers, including LC3, beclin-1, and AMPK. Rotenone inhibited autophagy, as indicated by decreased beclin-1 levels and increased mTOR levels, and this effect was reversed by calcitriol treatment.Discussion
Calcitriol protects against rotenone-induced neurotoxicity in SH-SY5Y cells by enhancing autophagy signaling pathways such as those involving LC3 and beclin-1. These neuroprotective effects of calcitriol against rotenone-induced dopaminergic neurotoxicity provide an experimental basis for its clinical use in the treatment of PD. 相似文献6.
Background
Dopamine neurons derived from induced pluripotent stem cells have been widely studied for the treatment of Parkinson's disease. However, various difficulties remain to be overcome, such as tumor formation, fragility of dopamine neurons, difficulty in handling large numbers of dopamine neurons, and immune reactions. In this study, human induced pluripotent stem cell-derived precursors of dopamine neurons were encapsulated in agarose microbeads. Dopamine neurons in microbeads could be handled without specific protocols, because the microbeads protected the fragile dopamine neurons from mechanical stress.Methods
hiPS cells were seeded on a Matrigel-coated dish and cultured to induce differentiation into a dopamine neuronal linage. On day 18 of culture, cells were collected from the culture dishes and seeded into U-bottom 96-well plates to induce cell aggregate formation. After 5 days, cell aggregates were collected from the plates and microencapsulated in agarose microbeads. The microencapsulated aggregates were cultured for an additional 45 days to induce maturation of dopamine neurons.Results
Approximately 60% of all cells differentiated into tyrosine hydroxylase-positive neurons in agarose microbeads. The cells released dopamine for more than 40 days. In addition, microbeads containing cells could be cryopreserved.Conclusion
hiPS cells were successfully differentiated into dopamine neurons in agarose microbeads.General significance
Agarose microencapsulation provides a good supporting environment for the preparation and storage of dopamine neurons. 相似文献7.
Eun Jeong Sohn Dae Won Kim Mi Jin Kim Hoon Jae Jeong Min Jea Shin Eun Hee Ahn Soon Won Kwon Young Nam Kim Duk-Soo Kim Kyu Hyung Han Jinseu Park Hyun Sook Hwang Won Sik Eum Soo Young Choi 《Biochimica et Biophysica Acta (BBA)/General Subjects》2012
Background
Oxidative stress is considered to be involved in a number of human diseases including ischemia. Metallothioneins (MT)-III can protect neuronal cells from the cytotoxicity of reactive oxygen species (ROS). However, MT-III proteins biological function is unclear in ischemia. Thus, we examined the protective effects of MT-III proteins on oxidative stress-induced neuronal cell death and brain ischemic insult.Methods
A human MT-III gene was fused with a protein transduction domain, PEP-1 peptide, to construct a cell permeable PEP-1–MT-III protein. PEP-1–MT-III protein was purified using affinity chromatograph. Transduced PEP-1–MT-III proteins were detected by Western blotting and immunoflourescence. Cell viability and DNA fragmentation were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-dipheyltetrazolium bromide (MTT) assay and terminal dexoynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining, respectively. Brain ischemic injury was detected with immunohistochemistry.Results
Purified PEP-1–MT-III proteins transduced into astrocytes in a time- and dose-dependent manner and protected against oxidative stress-induced cell death. Also, transduced PEP-1–MT-III proteins efficiently protected cells against DNA fragmentation. Furthermore, immunohistochemical analysis revealed that PEP-1–MT-III prevented neuronal cell death in the CA1 region of the hippocampus induced by transient forebrain ischemia. We demonstrated that transduced PEP-1–MT-III protein protects against oxidative stress induced cell death in vitro and in vivo.General significance
Transduced PEP-1–MT-III protein has neuroprotective roles as an antioxidant in vitro and in vivo. PEP-1–MT-III protein is a potential therapeutic agent for various human brain diseases such as stroke, Alzheimer's disease, and Parkinson's disease. 相似文献8.
Leucine methylation of protein phosphatase PP4C at C-terminal is critical for its cellular functions
Background
Protein phosphatase 4 (PP4) has been known to have critical functions in DNA double strand break (DSB) repair and cell cycle by the regulation of phosphorylation of its target proteins, such as H2AX, RPA2, KAP-1, 53BP1. However, it is largely unknown how PP4 itself is regulated.Methods
We examined the PP4C methylation on L307 at C-terminal by using methylated-leucine specific antibody. Then with PP4C L307A mutant, we explored that how nonmethylated form of PP4C affects its known cellular functions by immunoprecipitation, immunofluorescence, and DNA DSB repair assays.Results
Here we show that PP4C is methylated on its C-terminal leucine residue in vivo and this methylation is important for cellular functions mediated by PP4. In the cells PP4C L307A mutant has significantly low activity of dephosphorylation against its known target proteins, and the loss of interaction between L307A PP4 mutant and regulatory subunits, R1, R2, or R3α/β causes the dissociation from its target proteins. Moreover, PP4C L307A mutant loses its role in both DSB repair pathways, HR (homologous recombination) and NHEJ (non-homologous end joining), which phenocopies PP4C depletion.Conclusion
Our results demonstrate the key site of PP4C methylation and establish the physiological importance of this regulation. 相似文献9.
10.
Background
Iodothyronines are charged amino acid derivatives that cannot passively cross a phospholipid bilayer. Transport of thyroid hormones across plasma membranes is mediated by integral membrane proteins belonging to several gene families. These transporters therefore allow or limit access of thyroid hormones into brain. Since thyroid hormones are essential for brain development and cell differentiation, it is expected that genetic deficiency of such transporters would result in neurodevelopmental derangements.Scope of review
We introduce concepts of thyroid hormone transport into the brain and into brain cells. Important thyroid hormone transmembrane transporters are presented along with their expression patterns in different brain cell types. A focus is placed on monocarboxylate transporter 8 (MCT8) which has been identified as an essential thyroid hormone transporter in humans. Mutations in MCT8 underlie one of the first described X-linked mental retardation syndromes, the Allan–Herndon–Dudley syndrome.Major conclusions
Thyroid hormone transporter molecules are expressed in a developmental and cell type-specific pattern. Any thyroid hormone molecule has to cross consecutively the luminal and abluminal membranes of the capillary endothelium, enter astrocytic foot processes, and leave the astrocyte through the plasma membrane to finally cross another plasma membrane on its way towards its target nucleus.General significance
We can expect more transporters being involved in or contributing to in neurodevelopmental or neuropsychiatric disease. Due to their expression in cellular components regulating the hypothalamus–pituitary–thyroid axis, mutations and polymorphisms are expected to impact on negative feedback regulation and hormonal setpoints. This article is part of a Special Issue entitled Thyroid hormone signalling. 相似文献11.
Background
Administration of recombinant G-CSF following cytoreductive therapy enhances the recovery of myeloid cells, minimizing the risk of opportunistic infection. Free G-CSF, however, is expensive, exhibits a short half-life, and has poor biological activity in vivo.Methods
We evaluated whether the biological activity of G-CSF could be improved by pre-association with anti-G-CSF mAb prior to injection into mice.Results
We find that the efficacy of G-CSF therapy can be enhanced more than 100-fold by pre-association of G-CSF with an anti-G-CSF monoclonal antibody (mAb). Compared with G-CSF alone, administration of G-CSF/anti-G-CSF mAb complexes induced the potent expansion of CD11b+Gr-1+ myeloid cells in mice with or without concomitant cytoreductive treatment including radiation or chemotherapy. Despite driving the dramatic expansion of myeloid cells, in vivo antigen-specific CD8+ T cell immune responses were not compromised. Furthermore, injection of G-CSF/anti-G-CSF mAb complexes heightened protective immunity to bacterial infection. As a measure of clinical value, we also found that antibody complexes improved G-CSF biological activity much more significantly than pegylation.Conclusions
Our findings provide the first evidence that antibody cytokine complexes can effectively expand myeloid cells, and furthermore, that G-CSF/anti-G-CSF mAb complexes may provide an improved method for the administration of recombinant G-CSF.12.
Evangelia Pantazaka Evangelia Papadimitriou 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014
Background
Glycosylation is a multi-step post-translational enzymatic process which enhances the functional diversity of secreted or membrane proteins and is implicated in physiological and pathological conditions. Chondroitin sulfate (CS) chains are glycosaminoglycan chains, consisting of disaccharide units of glucuronic acid and N-acetylgalactosamine, attached to proteins as part of proteoglycans.Scope of Review
The existing knowledge on glycosylation by CS (CS glycanation) of cell membrane proteins and receptors, such as syndecans, chondroitin sulfate proteoglycan 4, betaglycan, neuropilin-1, integrins and receptor protein tyrosine phosphatase β/ζ, is summarized and the importance of CS glycanation in growth factor-induced migration, angiogenesis and tumor growth and invasion is described.Major Conclusions
Identification of glycosylation so far used to be a means of further characterizing and categorizing proteins and receptors. Although there is a significant amount of information regarding the interaction of growth factors with CS chains, very little information exists on the core proteins involved. It is now evident that there is more than meets the eye regarding the addition of glycans.General Significance
Future effort should focus on characterizing CS glycanation of membrane proteins and receptors of interest in an attempt to elucidate its contribution in fine-tuning growth factor-induced signaling. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties. 相似文献13.
Aims
Neuroprotective effects of maysin, which is a flavone glycoside that was isolated from the corn silk (CS, Zea mays L.) of a Korean hybrid corn Kwangpyeongok, against oxidative stress (H2O2)-induced apoptotic cell death of human neuroblastoma SK-N-MC cells were investigated.Main methods
Maysin cytotoxicity was determined by measuring cell viability using MTT and lactate dehydrogenase (LDH) assays. Intracellular reactive oxygen species (ROS) were measured using a 2,7-dichlorofluorescein diacetate (DCF-DA) assay. Apoptotic cell death was monitored by annexin V-FITC/PI double staining and by a TUNEL assay. Antioxidant enzyme mRNA levels were determined by real-time PCR. The cleavage of poly (ADP-ribose) polymerase (PARP) was measured by western blotting.Key findings
Maysin pretreatment reduced the cytotoxic effect of H2O2 on SK-N-MC cells, as shown by the increase in cell viability and by reduced LDH release. Maysin pretreatment also dose-dependently reduced the intracellular ROS level and inhibited PARP cleavage. In addition, DNA damage and H2O2-induced apoptotic cell death were significantly attenuated by maysin pretreatment. Moreover, maysin pretreatment (5–50 μg/ml) for 2 h significantly and dose-dependently increased the mRNA levels of antioxidant enzymes (CAT, GPx-1, SOD-1, SOD-2 and HO-1) in H2O2 (200 μM)-insulted cells.Significance
These results suggest that CS maysin has neuroprotective effects against oxidative stress (H2O2)-induced apoptotic death of human brain SK-N-MC cells through its antioxidative action. This report is the first regarding neuroprotective health benefits of corn silk maysin by its anti-apoptotic action and by triggering the expression of intracellular antioxidant enzyme systems in SK-N-MC cells. 相似文献14.
Hoon Jae Jeong Dae Young Yoo Dae Won Kim Hyeon Ji Yeo Su Bin Cho Jiye Hyeon Jung Hwan Park Jinseu Park Won Sik Eum Hyun Sook Hwang Moo-Ho Won In Koo Hwang Soo Young Choi 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014
Background
Oxidative stress is a leading cause of various diseases, including ischemia and inflammation. Peroxiredoxin2 (PRX2) is one of six mammalian isoenzymes (PRX1–6) that can reduce hydrogen peroxide (H2O2) and organic hydroperoxides to water and alcohols.Methods
We produced PEP-1-PRX2 transduction domain (PTD)-fused protein and investigated the effect of PEP-1-PRX2 on oxidative stress-induced neuronal cell death by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Western blot, immunofluorescence microscopy, and immunohistochemical analysis.Results
Our data showed that PEP-1-PRX2, which can effectively transduce into various types of cells and brain tissues, could be implicated in suppressing generation of reactive oxygen species, preventing depolarization of the mitochondrial membrane, and inhibiting the apoptosis pathway in H2O2-stimulated HT22, murine hippocampal neuronal cells, likely resulting in protection of HT22 cells against H2O2-induced toxicity. In addition, we found that in a transient forebrain ischemia model, PEP-1-PRX2 inhibited the activation of astrocytes and microglia in the CA1 region of the hippocampus and lipid peroxidation and also prevented neuronal cell death against ischemic damage.Conclusions
These findings suggest that the transduced PEP-1-PRX2 has neuroprotective functions against oxidative stress-induced cell death in vitro and in vivo.General significance
PEP-1-PRX2 could be a potential therapeutic agent for oxidative stress-induced brain diseases such as ischemia. 相似文献15.
16.
Severine Brule Véronique Friand Angela Sutton Françoise Baleux Liliane Gattegno Nathalie Charnaux 《Biochimica et Biophysica Acta (BBA)/General Subjects》2009,1790(12):1643-1650
Background
In addition to their physiologic effects in inflammation and angiogenesis, chemokines are involved in cancer pathology. The CXC-chemokine stromal cell-derived factor-1 (SDF-1)/CXCL12 mediates its biological activities through activation of G protein-coupled receptor CXCR4 and binds to glycosaminoglycans (GAGs).Methods
Using Bio-coat cell migration chambers, specific antagonists, flow cytometry and RNA interference, we evaluate the involvement of heparan sulfate proteoglycans (HSPG) in the SDF-1/CXCL12-induced invasion of human cervix epitheloid carcinoma HeLa cells.Results
The SDF-1/CXCL12-induced cell invasion is dependent on CXCR4. Furthermore, Protein Kinase C delta (PKC δ) and c-jun NH2-terminal kinase/stress-activated protein kinase (JNK/SAPK) are implicated in this event, but not extracellular signal-regulated kinase (ERK) 1/2. Moreover, the invasion of HeLa cells induced by SDF-1/CXCL12 was dependent on matrix metalloproteinase-9 (MMP-9). The pre-incubation of HeLa cells with heparin or with anti-heparan sulfate antibodies or with β-d-xyloside inhibited SDF-1/CXCL12-mediated cell invasion. Furthermore, the down-regulation of syndecan-4, a heparan sulfate proteoglycan, decreased SDF-1/CXCL12-mediated HeLa cell invasion. GAGs, probably on syndecan-4, are involved in SDF-1/CXCL12-mediated cell chemotaxis.General significance
These data suggest that targeting the glycosaminoglycan/chemokine interaction could be a new therapeutic approach for carcinomas in which SDF-1/CXCL12 is involved. 相似文献17.
Background
One of the signaling mechanisms mediated by nitric oxide (NO) is through S-nitrosylation, the reversible redox-based modification of cysteine residues, on target proteins that regulate a myriad of physiological and pathophysiological processes. In particular, an increasing number of studies have identified important roles for S-nitrosylation in regulating cell death.Scope of review
The present review focuses on different targets and functional consequences associated with nitric oxide and protein S-nitrosylation during neuronal cell death.Major conclusions
S-Nitrosylation exhibits double-edged effects dependent on the levels, spatiotemporal distribution, and origins of NO in the brain: in general Snitrosylation resulting from the basal low level of NO in cells exerts anti-cell death effects, whereas S-nitrosylation elicited by induced NO upon stressed conditions is implicated in pro-cell death effects.General Significance
Dysregulated protein S-nitrosylation is implicated in the pathogenesis of several diseases including degenerative diseases of the central nervous system (CNS). Elucidating specific targets of S-nitrosylation as well as their regulatory mechanisms may aid in the development of therapeutic intervention in a wide range of brain diseases. 相似文献18.
Eun Hee Ahn Dae Won Kim Min Jea Shin Hye Ri Kim So Mi Kim Su Jung Woo Seon Ae Eom Hyo Sang Jo Duk-Soo Kim Sung-Woo Cho Jinseu Park Won Sik Eum Soo Young Choi 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014
Background
PEA-15 is abundantly expressed in both neurons and astrocytes throughout the brain. It is a multifunctional protein with the ability to increase cell survival via anti-apoptotic and anti-proliferative properties. However, the function of PEA-15 in neuronal diseases such as Parkinson's disease (PD) remains unclear. In this study, we investigated the protective effects of PEA-15 on neuronal damage induced by MPP+ in neuroblastoma SH-SY5Y and BV2 microglia cells and in a MPTP-induced PD mouse model using cell-permeable PEP-1-PEA-15.Methods
PEP-1-PEA-15 was purified using affinity chromatography. Cell viability and DNA fragmentation were examined by MTT assay and TUNEL staining. Dopaminergic neuronal cell death in the animal model was examined by immunohistochemistry.Results
PEP-1-PEA-15 transduced into the SH-SY5Y and BV2 cells in a time- and dose-dependent manner. Transduced PEP-1-PEA-15 protected against MPP+-induced toxicity by inhibiting intracellular ROS levels and DNA fragmentation. Further, it enhanced the expression levels of Bcl-2 and caspase-3 while reducing the expression levels of Bax and cleaved caspase-3. We found that PEP-1-PEA-15 transduced into the substantia nigra and prevented dopaminergic neuronal cell death in a MPTP-induced PD mouse. Also, we showed the neuroprotective effects in the model by demonstrating that treatment with PEP-1-PEA-15 ameliorated MPTP-induced behavioral dysfunctions and increased dopamine levels in the striatum.Conclusions
PEP-1-PEA-15 can efficiently transduce into cells and protects against neurotoxin-induced neuronal cell death in vitro and in vivo.General significance
These results demonstrate the potential for PEP-1-PEA-15 to provide a new strategy for protein therapy treatment of a variety of neurodegenerative diseases including PD. 相似文献19.
Ludovic Carduner Rémy Agniel Sabrina Kellouche Cédric R. Picot Cécile Blanc-Fournier Johanne Leroy-Dudal Franck Carreiras 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
Intra-abdominal ascites is a complication of ovarian cancers and constitutes a permissive microenvironment for metastasis. Since fibronectin and vitronectin are key actors in ovarian cancer progression, we investigated their occurrence and molecular characteristics in various ascites fluids and the influence of these ascites-derived proteins on cell behavior.Methods
Fibronectin and vitronectin were investigated by immunoblotting within various ascites fluids. A combined affinity-based protocol was developed to purify both proteins from the same sample. Each purified protein was characterized with regard to its molecular features (molecular mass of isoforms, tryptophan intramolecular environment, hydrodynamic radii), and its influence on cell adhesion.Results
Fibronectin and vitronectin were found in all tested ascites. Several milligrams of purified proteins were obtained from ascites of varying initial volumes. Molecular mass isoforms and conformational lability of proteins differed according to the ascites of origin. When incorporated into the cancer cell environment, ascites-derived fibronectin and vitronectin supported cell adhesion and migration with various degrees of efficiency, and induced the recruitment of integrins into focal contacts.Conclusions
To our knowledge, this is the first combined purification of two extracellular matrix proteins from a single pathological sample containing a great variety of bioactive molecules. This study highlights that ascites-derived fibronectin and vitronectin exhibit different properties depending on the ascites.General significance
Investigating the relationships between the molecular properties of ascites components and ovarian cancer cell phenotype according to the ascites may be critical for a better understanding of the recurrence of this lethal disease and for further biomarker identification. 相似文献20.
Jill Harned Steven NagarM. Christine McGahan 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014