Scavenger Receptor Class B Membrane 1, also known as SR-BI plays an important role in lipid metabolism. Its main function is to mediate transfer of cholesterol between the cell surface and high density lipoprotein (HDL). HDL acts as an extracellular donor and acceptor of free and esterified Cholesterol. SR-BI also acts as a receptor for other ligands including lipoproteins, apoptotic cells and phospholipids. SR-BI is widely expressed and exists in high abundance in caveolae, which is highly enriched with cholesterol. SR-BI expression has been shown to increase cholesterol influx and efflux from HDL. Four isoforms have been described to be produced by alternative splicing of SR-BI. This protein also functions a receptor for Hepatitis C virus glycoprotein E2. The authors of the study ‘Scavenger receptor Class B is required for hepatitis C Virus uptake and cross-presentation by human dendritic cells.’ Barth, H., Schnober, E. K., et al. (2008) Journal of Virology, 82(7):3466-79 may have found a significant contribution to the design of Hepatitis C virus vaccines. Using SR-BI antibodies to identify the function of the protein they demonstrated that SR-BI antibodies inhibit the uptake of hepatitis C virus. They therefore identified SR-BI as a key factor required for the uptake of the virus. SR-BI has been found to be highly expressed on the cell surface of human dendritic cells. Using antibodies to bind to the protein on the cell surface the researchers found that cross-presentation by human dendritic cells was inhibited therefore demonstrating the need for SR-BI in this role.
Posts Tagged ‘Antibodies’
The TNF Alpha Antibody as a Therapeutic Tool
Thursday, July 14th, 2011Tumor necrosis factor alpha, or TNF alpha antibody products are widely used in cytokine and immunology research. TNF alpha is a pleiotropic ligand which plays an essential role in apoptosis, immune system development and the inflammatory response. We at Novus Biologicals have a number of TNF alpha antibody products in our catalog, which was recently enhanced by the addition of a new neutralising TNF alpha antibody. It is reactive against mouse, rat and rabbit tumour TNF-a, but not the human form of the antigen.
In nature, neutralising antibodies defend cells from attack by antigens by neutralizing their biological effects. Normally, binding antibodies flag antigens, signalling their destruction – a response which may be inhibited. Neutralising antibodies, however, specifically block the antigen’s effects. In 2003, Mark S. Freedman documented the effect of natural antibodies against IFN-beta, which was being investigated as a treatment for Multiple Sclerosis. He found that binding antibodies had no effect on the drug, whereas neutralizing antibodies blocked, or neutralised its action.
TNF alpha is expressed in a wide number of epithelial and immune cell types, and contains both a cytoplasmic and extracellular domain. Although essential for the inflammatory response, it is associated with a number of autoimmune disorders, including rheumatoid arthritis, Crohn’s disease and psoriasis. TNF-a inhibitors, in the form of TNF alpha antibody drugs such as Infliximab and Adalimumab, have proven highly effective against these diseases, but with variable success.
Research has revealed the body can actually produce neutralizing antibodies against these therapeutic TNF alpha antibody preparations (as happened with IFN-beta) so evidently a lot more work needs to be done.
Using the Ubiquitin Antibody in Disease Research
Monday, July 11th, 2011Ubiquitin is a small, highly conserved protein which plays an important role in protein breakdown, covalently bonding to proteins to mark them for proteolytic degradation in a process called ubiquitination. Ubiquitin also binds to inclusion bodies (accumulations of protein) in pathological conditions such as Parkinson’s and Alzheimer’s disease. Ubiquitin antibody products are therefore useful for identifying inclusions in neural research.
The Ubiquitin Proteasome Pathway, or UPP, is the principal method for protein degradation in normal cells, and central to the regulation of many cellular processes, including apoptosis; biogenesis; cell division; DNA transcription; cellular differentiation; modulation of ion channels, and DNA repair. Defects in the pathway have been linked to a number of important human diseases.
Protein degradation takes place in two stages: the protein is first covalently tagged by binding to multiple ubiquitin molecules, in a process known as conjugation, before being degraded by the 26S proteasome. Covalent linkage occurs as both single molecules and poly-ubiquitin chains, with the protein binding to lysine residues on the target protein via a series of enzymatically-controlled steps. Research with ubiquitin antibodies has shown the protein can also be conjugated to itself, resulting in diverse chain linkages. Initially, the protein was thought to play a “housekeeping” role, regulating antigenic-peptide generation and protein turnover. However, recent ubiquitin antibody studies have identified non-degenerative roles in, for example, endocytosis and DNA repair.
Ubiquitin antibodies are widely used in immunohistochemistry to identify abnormal protein inclusions. These include the neurofibrillary tangles of Alzheimer’s disease; Lewy bodies of Parkinson’s disease; Mallory bodies in alcoholic liver disease and Pick disease Pick bodies. The ubiquitin antibody can also identify the Rosenthal fibers of astrocytes.
The Adiponectin Antibody and Breast Cancer Research
Friday, June 17th, 2011Adiponectin (also called ADIPOQ) is a cytokine expressed exclusively in adipose tissue. It has a number of functions, regulating lipid metabolism, gluconeogenesis and the inflammatory response. Adiponectin antibody products are widely used in diabetes, obesity and lipid metabolism research. Obesity and Type 2 Diabetes are linked to an increased risk of breast cancer in women. New adiponectin antibodies recently proved important in this area of research.
Adiponectin levels are inversely related to adiposity and development of Type 2 Diabetes. Adiponectin antibody research has also revealed a strong link between ADIPOQ expression and breast cancer risk, with decreased blood serum levels linked to increased risk of breast cancer in obese patients, and vice versa. Adiponectin antibody studies have also suggested the protein may regulate TNF, IGF and oestrogen secretion.
Adiponectin binds to several receptors, including ADIPOR1 and R2. In 2003 Miyoshi, Funahashi et al showed ADIPOR1/R2 expression in certain breast cancer cell lines, although proliferation was reduced when cells were exposed to ADIPOQ. Further studies revealed ADIPOQ and ADIPOR1 single nucleotide polymorphisms (SNPs) could affect expression of the protein, and were associated with increased risk of insulin resistance, diabetes mellitus and cardiovascular disease.
In 2008, V. Kaklamani et al examined the role of these SNPs in breast cancer development, in a case control study involving both breast cancer patients and healthy volunteers. Genotyped haplotype-tagging methods revealed a strong correlation between raised ADIPOQ/R1 SNP levels and increased breast cancer risk.
We at Novus Biologicals recently added new adiponectin and adiponectin R1 antibodies to our catalog, to further research in this area.
The Role of the MMP2 Antibody in Colorectal Cancer Research
Monday, June 13th, 2011The enzymes of the Matrix Metalloproteinase (MMP) family assist in the degradation of the extracellular matrix, under both normal and pathological conditions. MMP antibodies have identified roles in a number of physiological processes, such as embryonic development and tissue remodelling. They also regulate enzyme cascades, expression of various proteins and the migration of both normal and malignant cells.
The MMP2 antibody is used in a number of research areas, including metastasis, angiogenesis, apoptosis and tumour suppression. MMP2 antibody studies have shown MMP2 plays a specific role in the degradation of collagens and gelatin1. It also functions in angiogenesis, tissue repair, vascularization, inflammation, atherosclerotic plaque rupture, endometrial menstrual breakdown and tumour metastasis. It is secreted in inactive form, being activated by proteinase cleavage via the Ras signalling pathway.
In 2001, S. Papadopoulou et al published MMP2 antibody research which used immunohistochemical staining techniques to compare MMP2 levels in both normal human colon mucosa and colorectal cancer cells. Both tissues showed immunohistological localization of MMP2. However, antigen levels were significantly higher in the tumour cells, with staining intensity higher in malignant adenocarcinomas than benign adenomas.
Recently, K.S Park et al used MMP2, MMP9 and TIMP2 (tissue inhibitor of metalloproteinase-2) antibodies to identify gene profiles which may increase the risk of colorectal cancer. Specific SNPs (single-nucleotide polymorphisms) were identified in both TIMP2 and MMP2, which were associated with tumourigenesis. M.J Kang et al have also used MMP2 antibody products to probe the relationship of MMP2 SNPs to SNPs in VEGF and HIF1A, but no association was found.
We at Novus Biologicals have a wide range of MMP2 antibody products, which are constantly being updated.
BDNF Antibodies and Synaptic Research
Friday, May 6th, 2011Brain-derived neurotrophic factor (BDNF) is a member of the NGF family of neurotrophins. During development it regulates the survival and differentiation of neuronal cell populations in the central and peripheral nervous system, while in adult synapses it is a major regulator of development, plasticity and transmission. We at Novus Biologicals are a leading antibody supplier for neurological research, with an extensive range of BDNF antibodies.
BDNF, like NGF, is a non-covalently linked homodimer, with an identical amino acid sequence in all known mature mammals. It is expressed at high levels in the hippocampus, cerebellum, placenta and foetal eye, and to a lesser extent in the pituitary gland, lung, spinal cord and skeletal and cardiac muscle.
BDNF plays an important role in adaptive neuronal responses, including long-term potentiation and depression, and short-term synaptic plasticity. It also plays a role in homeostasis, regulating intrinsic neuronal excitability. BDNF expression may be altered by such things as stress, seizures, ischemia and hypoglycemia. Modified BDNF expression has been linked to neuropathological disorders such as depression, Alzheimer’s, epilepsy and Parkinson’s disease.
Recent BDNF antibody studies have concentrated on activity-dependent changes (ADCs) to BDNF expression following synaptic transmission. ADCs are dependent on calcium influx, which induces transcription factors to bind nuclear calcium-response elements (CaREs).
In 2008, BDNF antibody research by Hong et al. showed that activity-dependent BDNF expression was linked to CaRE expression and synaptic plasticity. In 2009, Kuczewski et al. suggested BDNF functions as a target-derived messenger for activity-dependent synaptic plasticity. These experiments were dependent on products of the highest quality, supplied by leading antibody suppliers like Novus Biologicals.
Featured Product Citation using Novus’ hTERT Antibody
Monday, May 2nd, 2011In the article “Mesenchymal stem cells derived from human gingiva are capable of immunomodulatory functions and ameliorate inflammation-related tissue destruction in experimental colitis” from the December 2009 edition of the Journal of Immunology, Dr. Qunzhou Zhang et al. cite using Novus’ mouse monoclonal Telomerase Reverse Transcriptase Antibody (cat# NB100-317). Specifically, Novus’ hTERT antibody is used for immunofluorescent staining on human gingiva-derived mesenchymal stem cells (GMSC). Novus’ hTERT specific antibody helps the authors demonstrate that the GMSC’s are in fact a new population of precursor cells “which exhibit several unique stem cell-like properties as MSCs derived from bone marrow and other postnatal tissues.”
Novus Biologicals offers a complete line of Telomerase Reverse Transcriptase antibodies for Western blot, immunostaining, flow cytometry and immunoprecipitation. Novus also offers hTERT lysate, hTERT antibody pack, hTERT RNAi, and ancillary reagents for your hTERT research. Finally, you may find a wide range of other cellular markers and antibodies related to DNA repair online at www.novusbio.com.
Zhang Q, Shi S, Liu Y, et al. Mesenchymal stem cells derived from human gingiva are capable of immunomodulatory functions and ameliorate inflammation-related tissue destruction in experimental colitis. J Immunol. 2009 Dec 15; 183 (12): 7787-98. [PMID: 19923445]
TNF Alpha Antibodies as Therapeutic Tools
Monday, February 14th, 2011Tumor Necrosis Factor (TNF) alpha is a cytokine protein that plays an essential role in inducing the systemic inflammatory response, being expressed in tissues throughout the body. In autoimmune diseases such as rheumatoid arthritis and psoriasis, TNF alpha causes negative clinical effects. These can be controlled by inhibitory TNF antibody drugs, a number of which are now on the market. We at Novus Biologicals have an extensive range of TNF alpha antibodies.
TNF alpha is expressed by a number of cell types, primarily macrophages. TNF antibody research has shown the protein to have a number of effects, both positive and negative. In mice, it causes tumour necrosis when injected into tumour sites, and studies have shown it can inhibit tumour growth, induce apoptosis, and inhibit viral replication. It has also shown a cytotoxic role in cells which have undergone genetic alteration, but can be toxic in vascular endothelial cells. It can stimulate growth and proliferation of certain cell lines, including fibroblasts, neutrophils and osteoclasts. Mutations of the TNF alpha gene are linked to a number of diseases, including cancer, while overexpression of the normal protein can lead to toxic shock and endotoxemia.
While TNF alpha antibody therapy is proving useful in combating autoimmune disease, the recombinant protein has also proven useful, being released as an immunostimulant, under the international non-proprietary name of Tasonermin. Studies are also being conducted into its use as a therapeutic tool in cancer and AIDS.
Recent research into the therapeutic use of TNF antibodies has centred on the skin disorder hidradenitis suppurativa. In 2009, Haslund et al published research showing promising results with the TNF alpha antibody products Infliximab, Adalimumab and Etanercept.
New Drosophila Model Developed for Direct in Vivo Study of Histones
Monday, November 29th, 2010Forming the major protein component of chromatin, histones are essential to the structure and organisation of chromosomes, forming the nucleosome around which DNA is packaged and wrapped.
Antibody studies have revealed histones undergo various posttranslational modifications which affect their interaction with DNA and nuclear proteins, allowing them to play diverse roles in biological processes such as cell division, gene regulation and DNA repair. For example, the outer “tail” of H3 and H4, and central core of H2A, H2B and H3 can undergo covalent modification via methylation, ubiquitination, phosphorylation and many other routes. These modifications constitute an epigenetic “histone code,” denoted by the name of the protein, the amino acid modified, and the type of modification. For example, H3K4me1 tells us that the histone H3 underwent monomethylation of lysine residue 4 (denoted by K4).
Research of histone modification in higher eukaryotes has been hampered by lack of a suitable experimental model. Now, researchers at Göttingen’s Max Planck Institute have succeeded in creating a genetic system that enables direct observation of histone modification and function in fruit flies, allowing both in vitro and in vivo effects to be studied. The system involves replacing the canonical histone complement of the flies with experimentally modified and coded histones from other organisms. This provides a direct cellular and antibody assay system, allowing in-depth analysis of histone modification on chromatin assembly, cell function, cell division and many other aspects of cell biology.
We at Novus Biologicals anticipate this new genetic tool will generate a lot of excitement among users of our antibody database.
ATXN2 Identified as New Genetic Risk Factor for Lou Gehrig’s Disease
Friday, November 19th, 2010Ataxin antibodies are used in the study of autosomal dominant cerebellar ataxia (ADCA) diseases. These neurodegenerative disorders are highly heterogeneous, characterised by progressive, irreversible, atrophy of the cerebellum and spinal cord.
Ataxin-2 is encoded by the ATXN2 gene, mutation of which can lead to Spinocerebellar Ataxia Type 2 (SCA2). Recently, Ataxin-2 antibodies were used in an international study that showed ATXN2 to be a genetic risk factor in another neurodegenerative disorder – Amyotrophic lateral sclerosis (ALS) or Lou Gehrig’s disease. The mutation causing SCA2 is identified by expanded CAG repeats in the coding region of ATXN2. The expansion is extremely variable in size, but averages 34-52 repeats; it results in an elongated polyglutamine tract (called a polyQ expansion) in encoded Ataxin-2.
A team led by scientists from the University of Pennsylvania searched for similar mutations in the DNA of neurons from ALS patients. This followed earlier antibody research in yeast cells, which showed Ataxin-2 to modify toxicity of the gene TDP-43. TDP-43 mutations are known to cause spinocerebellar ataxia with axonal neuropathy (SCAN1), as well as ALP. Antibody assays using a fruit fly model confirmed Ataxin-2 to be a potent TDP-43 modifier, with TDP-43 toxicity increasing comparative to the level of Ataxin-2 present.
In neurons of human ALP patients, it was discovered that Ataxin-2 underwent a PolyQ mutation similar to that of SCA2, with a strong genetic correlation between expanded CAG repeats and risk of ALS. The expansions were shorter than those of SCA2, but longer than controls. This newly-found association between ATXN2, TDP-43 and ALS is an exciting one, and we at Novus Biologicals anticipate a rash of new biomarkers being added to our antibody catalog.