Posts Tagged ‘Antibody studies’

The CD4 Antibody – More than Just a Useful Cellular Marker

Friday, April 8th, 2011

CD4 is a member of the cluster of differentiation family of proteins, mainly expressed on the surface of thymocytes and a specific subset of mature T-cells. CD4 antibody studies have also shown it expressed on monocytes, cortical cells, microglial cells, dendritic cells and macrophages. The CD4 antibody is widely used in cell marker studies, CD4 being one of the most common CD markers in use. However, the CD4 products in our antibody catalog have also proven useful in cell biology, immunology and cytokine research.

CD4 is a co-receptor for the TCR (T Cell Receptor) heterodimer. It has both intracellular and extracellular domains. The intracellular domain amplifies TCR signalling by activating the tyrosine kinase LCK enzyme, essential to the activated T cell signaling cascade. The four extracellular domains interact directly with MHC class II molecules, which are released by antigen-presenting cells. The main function of CD4 is to increase interaction between the TCR and antigen-class II MHC complex.

CD4 antibody studies have shown CD4, together with CD3 chains and the CD8 co-receptor, aids signal transduction through the TCR. The CD4 antibody is useful in distinguishing T-helper from T-cytotoxic cells, both of which express the TCR, as CD4 is specific to T-helper cells while CD8 is expressed on T-cytotoxic cells.

The CD4 antibody is central to HIV research, as the viral envelope protein achieves entry into the host cell by CD4 binding, lowering CD4 levels. The CD4 antibody is routinely used in the CD count test, used to monitor CD levels in HIV positive patients.

We at Novus Biologicals have a wide range of CD4 antibody products in our antibody catalog.

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The GAPDH Antibody – a Diverse Area of Research

Monday, March 21st, 2011

The glyceraldehyde 3-phosphate dehydrogenase, or GAPDH enzyme plays an important role in the conversion of glucose for energy, catalyzing the sixth step of the glycolytic pathway. A common and widely expressed protein, GAPDH mRNA is often used as a standard in mRNA studies. GAPDH antibody products are also used as a loading control in Western blot assays. We at Novus Biologicals have 55 GAPDH antibody products on our antibody database.

GAPDH catalyses the reversible oxidative phosphorylation of glyceraldehyde 3-phosphate, yielding D-glycerate 1, 3-bisphosphate in a two-step process which couples phosphorylation to oxidation. Recent GAPDH antibody studies have suggested GAPDH also has a role to play in several non-metabolic processes, including transcription activation, ER to Golgi vessel shuttling and apoptosis. GAPDH is known to bind to a number of other proteins, including the amyloid precursor protein, mutations of which can cause Alzheimer’s disease.

In 2003, Zheng et al identified a transcriptional role for GAPDH, forming part of the OCA-S Oct-1 coactivator complex in combination with lactate dehydrogenase. It this study, GAPDH directly bound to Oct-1, and selectively bound to the H2B promoter during the S-phase. Other GAPDH antibody studies have suggested GAPDH plays a role in basal RNA polymerase II transcription, and also DNA repair.

In 2005, Hara et al showed that GAPDH initiates apoptosis in response to cellular stress, binding to the E3-ubiquitin ligase Siah1 following S-nitrosylation. In 2006, the same group showed that Deprenyl, a drug used to treat Parkinson’s disease, blocked S-nitrosylation of GAPDH, preventing Siah1 binding.

Neurodegeneration and apoptosis are closely intertwined. The GAPDH antibody database may turn out to be a useful tool in the fight against neurodegenerative disorders such as Alzheimer’s, Huntington’s and Parkinson’s disease.

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Bitter Taste Receptor Antibodies Used in New Bronchodilator Study

Thursday, December 23rd, 2010

As one of the world’s leading antibody suppliers, we at Novus Biologicals have an expansive GPCR (G-protein coupled receptor) antibody catalogue. Recently one of its reagents, the bitter taste receptor (TAS2R) antibody, was used in a study showing TAS2R bronchodilator activity in human airways.

The G-protein Gustducin plays an important role in the transduction of gustatory (taste) stimuli, especially with respect to bitter stimuli. TAS2R is linked to Gustducin and is thought to play a role in bitter taste detection. Antibody studies suggest it may mediate alpha gustducin expression and PLC-beta-2 activation, and be involved in TRPM5 gating.

TAS2R receptors are thought to be expressed exclusively in gustducin-positive cells on the tongue, and to have evolved as a protective mechanism against plant toxin ingestion. However a new study, conducted by D.A Deshpande et al, reported TAS2R receptors on the smooth muscle of human airways (ASM). They considered the purpose might similarly be as avoidance receptors, against inhaled toxins which could lead to bronchospasm by smooth muscle contraction.

They noted that bitter tasting TAS2R agonists, including saccharin, chloroquine and denatonium, induced enhanced levels of intracellular calcium (Ca2+) in ASM cells. The receptors involved were the same as those engaged in the contraction response. However, the bitter tasting agonists actually caused relaxation in isolated cells, with airways dilation three times greater than that seen with Beta agonist drugs such as Salbutamol.

It was suggested that TAS2R-induced relaxation occurred as a result of a localised Ca2+ response at the cell membrane. This led to the opening of large-conductance Ca2+ activated potassium channels, leading to hyperpolarisation of the smooth muscle membrane. A mouse model of bronchocontraction supported this. It is hoped further TAS2R antibody studies will lead to the development of novel bronchodilator therapies.

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PTEN Antibodies and Cancer Research

Thursday, December 9th, 2010

Phosphatase and tensin homologue (PTEN) antibodies are important tools for cancer research. PTEN is an important tumour suppressor but, in mutated form, is also expressed in a high number of cancers. We at Novus Biologicals have a wide PTEN antibody database, with 50 antibodies, proteins and lysates to choose from.

PTEN encodes a lipid phosphotase protein (a phosphatidylinositol-3, 4, 5-trisphosphate 3-phosphatase) which is involved in cell cycle regulation, controlling cell growth and proliferation. This also allows it to act as a tumour suppressor. The protein has a similar structure to the protein tyrosine phosphatases, a group of dual-specificity enzymes which regulate phosphorylation of cell-signalling cascades. However, it differs in showing preferential dephosphorylation, negatively regulating phosphatidylinositol-3, 4, 5-trisphosphate (PIP3) by dephosphorylation at the D position.

The function of PIP3 is to activate downstream signalling of AKT, which is known to regulate a number of cell signalling pathways involved with cell growth and survival. This includes the Akt/PKB pathway, which is implicated in a number of cancers. PIP3 dephosphorylation enables PTEN to negatively regulate the Akt/PKB pathway, and in this way control cell proliferation and suppress tumour growth.

An antibody research study published by DeFeo Jones et al in 2005 showed that selective inhibition of the Akt/PKB pathway was important in tumour suppression, sensitizing tumour cells to apoptotic stimuli. The absence of PTEN function, for example by mutation, can lead to enhanced Akt activity and resistance to apoptosis – an important factor in tumour progression. In March 2010, Leone, Ostrowski et al showed a strong link between inherited PTEN mutations and Cowden syndrome, a condition associated with a high incidence of cancers.

PTEN is one of the most frequently mutated tumour suppressor genes in human cancer, and our PTEN antibody database continues to play an important part in cancer studies.

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Arrestin Antibodies Used in New Serotonin Syndrome Study

Tuesday, December 7th, 2010

The beta-arrestin family regulate receptor binding of G-proteins, a group of seven transmembrane receptor proteins which includes the adrenergic, dopamine and serotonin receptors. Recently, arrestin antibodies were used in a study into Serotonin Syndrome, a hallucinogenic disorder which can follow SSRI (selective serotonin reuptake inhibitor) use.

The beta-arrestin family are found at postsynaptic receptor sites, where they interact with GRK 2 and GRK3 proteins to desensitise G-protein-coupled receptors, dampening the cellular response to stimuli such as hormones, neurotransmitters and sensory signals. For example, S-arrestin/beta-arrestin1 is a soluble photoreceptor protein highly expressed in the retina of the eye, as well as the pineal gland. Encoded by the SAG gene, it plays a desensitization role in the photoactivated transduction cascade, inhibiting the coupling of transducin to rhodopsin – an essential stage in the conversion of light into receivable electrochemical signals.

Recently, C. Schmidt et al, of the Scripps Research Institute, used beta-arrestin antibodies to investigate hallucinations arising as a result of prescribed and recreational drugs. Serotonin signalling at the serotonin 2A receptor site was shown to be specifically controlled by beta-arrestin2. Behavioural studies revealed that head-twitching – a common effect of serotonin 2A activation – was also seen in animals given the hallucinogenic drug N-methyltryptamine. However, although it activated the same receptor as serotonin (S-2A), the hallucinogen was not recognised by beta-arrestin2. This proved serotonin utilises a very specific pathway, with side-effects independent of those caused by hallucinogens.

The results supported a hypothesis that serotonin-induced hallucinations are caused by metabolites generated as a result of elevated serotonin levels. Future antibody studies could look at methods of preserving serotonin’s beneficial effects, while blocking the unwanted side effects of its metabolites.

We at Novus Biologicals have a large antibody database covering this area of research.

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SEPT4 Gene Could Prevent Stem Cell Cancer

Monday, November 15th, 2010

The antibodies in our stem cell antibody catalogue are used in many areas of research, from developing therapies to investigating cancer. The two are related, because although pluripotent stem cells have the potential to replace organ transplants and heal paralysis, they also have the potential to develop into both healthy and cancerous cells. Now, researchers at the Rockefeller University have discovered a link between stem cell apoptosis and tumour development in mice.

Cancer stem cells (CSCs) have been identified in many human cancers. Antibody studies have shown CSCs can accelerate cell proliferation, increase DNA-repair mechanisms and block apoptosis. The development of stem cell marker antibodies to these proteins is an important area of CSC research.

Garcia-Fernandez et al, of the Strang Laboratory, decided to look at the SEPT1 gene, which in humans encodes ARTS, a mitochondrial protein known to promote TGF-Beta induced apoptosis and antagonise IAPs (inhibitor of apoptosis proteins). SEPT4 is often under-expressed in cancers, pointing to a tumour suppressor role.

The study compared hematopoietic stem cells (HSCs) in ARTS-deficient newborn mice to those of normal controls. Previous antibody studies focussing on mature cells had shown no difference between the groups. However, in stem cell populations the difference was pronounced, with ARTS-deficient mice having roughly 50% more HSCs and progenitors than the controls. These cells were able to survive experimentally- induced apoptosis to a high degree, with a 50% increase in spontaneous tumour development over controls. This suggested premature silencing of the SEPT4/ARTS pathway in stem cells can lead to increased apoptosis resistance and cancer development.

This is the first antibody study to show a definite link between HSC apoptosis and tumour susceptibility. We at Novus Biologicals have over 65 products related to SEPT4 on our antibody database.

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New Study Links Tau Mutations to Microglial Immune Response

Monday, November 8th, 2010

Tau proteins are abundant in the axons of neurons in the central nervous system (CNS), and play a key role in microtubule formation and stabilization. Antibody studies have identified six tau isoforms, all produced by alternative mRNA splicing of the MAPT gene. We at Novus Biologicals have almost 160 antibodies matched to tau proteins on our antibody database.

Tau mutations can give rise to a number of neurodegenerative disorders, such as the taupathies. These are characterized by the formation of hyperphosphorylated filamentous aggregates, and tangles of paired helical filaments such as those found in the brain cells of Alzheimer’s disease patients.

Recent studies have suggested that microglial cells, which are essential to CNS immunity, may also be involved in neurodegenerative disorders. Some antibody studies have suggested a link between the neuroinflammatory immune response instigated by microglial cells, and tauopathy. However there has been little evidence connecting the two together. Now, a study by Lamb, Bhaskar et al, of the Cleveland Clinic Foundation, has come up with new evidence supporting a link between microglial activity and abnormal MAPT expression.

The study focussed on the Fractaline signalling pathway, which binds the neural chemokine CX3CL1 to its receptor CX3CR1, which is expressed in the microglia. Using a range of in vivo and in vitro models, it was shown that microglial inflammation triggered MAPT phosphorylation and tau aggregation. CX3CR1 deficiency in hTau mice resulted in increased MAPT phosphorylation and aggregation, alterations in microglial activation, and behavioural abnormalities. This study has provided important new information on the nature of the CX3CL1/CX3CR1 pathway, and confirmed a link between microglial activation and MAPT hyperphosphorylation and aggregation. This is useful new information for those using our antibody catalog for Alzheimer’s disease research.

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Activation of NF-Kappa B via Coordination of cIAP, TRAF and Kinase NIK

Thursday, March 11th, 2010

Recent antibody studies have suggested that nuclear factor κB-inducing kinase (NIK) is inhibited through proteasome-controlled degradation regulated by TRAF/cIAP proteins. cIAP1 and cIAP2 are fairly recent apoptosis inhibitors and represent some of the newer products in our antibody catalog.

NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) is found in practically all mammalian cells and is a transcriptional factor of DNA. It affects the cellular response to a range of stimuli, including free radicals, UV radiation and stress. It plays an important role in the immune response to pathogens, but disruption of the regulatory pathways can lead to cancer and other diseases.

The TNF receptor-associated factor (TRAF) family are adaptor proteins which link various cell receptors to MAPK signaling cascades, thus activating NF-kB. TRAF proteins are important transducers for the TNF and the IL-1/TLR receptor complexes. They play an important role in the adaptive and innate immune responses.

The C-terminals of TRAF2 and TRAF3 interact with receptor domains following ligand-induced oligomerization. They interact with a number of pro and anti-apoptosis proteins, meaning TRAF signaling can promote either cell death or survival. The cell signaling proteins in our antibody catalog are used for both pro and anti-apoptosis studies in both healthy and cancerous cells.

Recent IHC assays showed that NIK degradation was dependent on a TRAF3/NIK, TRAF2/cIAP1 and TRAF2/cIAP2 regulatory complex. cIAP1 and cIAP2 appeared to play redundant roles in NIK degradation, as deactivation of both proteins was required for non-canonical NF-kB activation and B-lymphocyte survival. The NIK pathway is tightly regulated, meaning a single gene is enough to reverse lethal TRAF deficiency.

Our antibody catalog at Novus Biologicals is constantly being updated to reflect new signaling pathway findings.

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