Posts Tagged ‘Antibody suppliers’

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Recent Bax Research Gives New Insight Into Oxidative Apoptosis

Wednesday, July 20th, 2011

Bax is a member of the Bcl-2 family; an extensive range of proteins which play key roles in apoptosis, or programmed cell death, by regulating outer mitochondrial membrane permeability. We at Novus Biologicals are one of the leading antibody suppliers for apoptosis research, with an extensive range of Bax antibody products.

The Bcl-2 proteins share one or more conserved domains (BH1 – 4.) They are divided into three subfamilies based on their function and domain: Antiapoptotic (i.e. pro-survival); proapoptotic multidomain, and proapoptotic BH3-domain only. The BH domains are essential to heterodimerisation between family members. Cellular homeostasis is maintained by the balance of activity between pro- and antiapoptotic proteins.

Bax (derived from Bcl-2–associated X protein) was the first identified member of the multidomain proapoptotic family. It promotes apoptosis by competing with Bcl-2 proper, an antiapoptotic protein. The Bcl-2 and Bax antibody are of great importance in cancer research, as alterations to expression of competing Bcl-2 proteins are known to be a cause of many malignancies. The Bcl-2 family is also implicated in a number of other conditions including diabetes, Down’s Syndrome and AIDS.

Bax antibody research has shown the protein resides in the cytosol, undergoing translocation to the outer mitochondrial membrane after apoptosis is initiated. Its mode of action is uncertain, but evidence suggests Bax and/or Bak form an oligomeric pore, called MAC, activating mitochondrial permeabilisation and the release of caspases, such as cytochrome C. This initiates apoptosis.

Recently, scientists at the Medical College of Wisconsin, United States suggested Bax permeabilization was achieved by cardiolipin (CL) translocation from the inner to the outer membrane. Cytochrome c is released early in the apoptosis pathway, following CL oxidation.

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Notch Antibody Proves Metastatic Lung Cancer Has a Jagged Edge

Wednesday, June 29th, 2011

We at Novus Biologicals are one of the leading antibody suppliers for cancer research. In a recent Notch antibody study, the Notch ligand Jagged2 was found to promote the growth of metastatic lung cancer cells by inhibiting miR-200, which blocks epithelial-to-mesenchymal transition (EMT) – an early stage in metastasis which, if blocked, can prevent secondary tumour growth.

The Notch proteins are large single-pass transmembrane receptors, important to embryonic development cell signalling. It comprises an intracellular and extracellular domain, the latter being composed of EGF-like repeats and cysteine-rich Notch/Lin-12 repeats. Notch signalling is initiated following Delta or Jagged1/2 ligand binding. Antibody studies have shown this results in cleavage of the extracellular domain, initiating translocation of the intracellular fragment to the nucleus, triggering transcription of various genes.

The Notch proteins have a large number of positive and negative regulators, which work by binding the ankyrin repeat region of the intracellular domain. Notch antibody studies have shown the promoter binding factor CBF1 is bound at the ankyrin repeat and RAM domain. The Notch/CBF1 complex is able to affect access the genome to activate transcription via histone acetylase/deacetylase activity.

In the recent study, Yang et al used Jagged2, GAT and Notch antibody products to investigate the role of Notch in lung tumour metastasis, using a mouse model. They discovered Notch2 controls expression of GATA3, a protein which works in counter-inhibitory fashion with the microRNA miR-200. In knock-down studies, suppression of Jagged2 or overexpression of GATA3 led to increased levels of miR-200, preventing metastasis from occurring.

If you need reliable antibody suppliers for metastasis research, we have an extensive database of high quality Notch antibody products.

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The Osteopontin Antibody and Hepatic Research

Monday, May 23rd, 2011

Antibody suppliers, such as us at Novus Biologicals, supply a wide range of cell marker products, among them the osteopontin antibody. Recently, the osteopontin antibody has proven useful in hepatic cancer research.

Osteopontin (OPN) is mainly expressed by the osteoblasts; its primary function is in the mineralization of bone. However, OPN is expressed to a lower degree in other areas of the body, being involved in cell adhesion, cell migration and the inflammatory response.

Osteopontin has been implicated in a number of inflammatory diseases including rheumatoid arthritis (RA), multiple sclerosis and hepatitis. It is also upregulated in a number of cancers. Osteopontin antibody studies have shown OPN is modified in a number of tissue-specific ways, including phosphorylation, glycosylation, sulphation and transglutamination.

OPN is known to have two central domains with multiple integrin binding sites, which are activated following thrombin-induced cleavage. Cleavage can also be initiated by MMP proteins at central and C-terminal sites, although C-terminal binding seems to have no integrin effect. Importantly, OPN can undergo complete digestion by MMP-9, resulting in the release of a 5 kDa fragment. In 2007, Takafuji et al published a study showing this fragment to play a role in the development of hepatocellular carcinomas, promoting CD44-mediated metastasis.

Administration of neutralizing murine osteopontin antibody has proven successful in treating RA and fulminant hepatitis in mice, but is of little clinical use in humans. Recently, B. Zhang et al succeeded in ‘humanising’ a murine osteopontin antibody, while retaining full binding affinity. The study strongly suggested humanized anti-osteopontin antibody may have a therapeutic use in humans, though it must be stressed the products sold by antibody suppliers are for research use only.

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HA-tag Antibody

Monday, March 14th, 2011

We at Novus Biologicals are one of the leading antibody suppliers of high affinity human epitope tag reagents, such as the HA tag antibody. Widely used in Western blot, ELISA and Immunohistochemistry assays, they offer a useful and reliable method for detecting, analyzing and purifying proteins from a wide range of species.

Short, immunoreactive epitope tags are highly useful reagents. They are small, so unlikely to interfere with the protein under test, but have a high degree of immunoreactivity, due to the fact they are generally derived from viral genes. The HA tag, for example, is derived from amino acids 98-106 of the human influenza haemagglutinin (HA) protein, an antigenic glycoprotein found on the surface of the human influenza virus.

Developed around 20 years ago, the HA tag can be expressed from a wide range of engineered recombinant proteins, and is widely used as a general epitope tag for expression vectors. The HA tag antibody recognizes overexpressed HA-tagged proteins in a wide range of cells, including transfected mammalian cells. For easy immunochemical analysis and visualization, it is usually engineered onto the N (amino) or C (carboxy) terminus of the protein being studied.

The HA tag antibody has proven invaluable in human disease research, being extensively used in both biochemistry and cell biology to track and isolate proteins, and precipitate them with other proteins in the pathway. They have proven invaluable in the complex field of apoptosis. However, in 2007 H. Zhang et al reported HA tag cleavage and loss of immunoreactivity during apoptosis. Luckily, antibody suppliers like us have plenty of alternatives, such as c-Myc and V-5 epitope tags.

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Caspase Antibody Study Shows Link to Heart Disease

Monday, February 28th, 2011

Caspase 3 is a member of the cysteine-aspartic acid protease family and an important mediator of apoptosis. Caspase 3 antibody reagents have been used in cancer, Alzheimer’s disease and stem cell research. A recent caspase 3 antibody ELISA study showed elevated levels of the p17 caspase 3 fragment were associated with myocardial infarction in humans. We at Novus Biologicals are one of the leading antibody suppliers of caspase products.

Caspase 3 is one of the effector group of caspases, initiating DNA fragmentation and chromatin condensation in apoptosis, via substrate cleavage following activation by either death ligand or mitochondrial action. It interacts with initiator caspases 8 and 9, and plays a predominant role in the cleavage of amyloid-beta 4A, which has been linked to neuronal cell death in Alzheimer’s patients. As well as its role in apoptosis, caspase 3 is now known to be important to normal brain cell development, and may be involved in the differentiation of embryonic and hematopoietic stem cells.

Research into acute Myocardial Infarction (AMI), has shown apoptosis of cardiac monocytes to follow development of infarcts in animal models. However, results have been uncertain in human patients. In January 2011, Mariela Agosto et al published a paper showing serum caspase 3 p17 fragments were elevated in patients with ST-segment elevation Myocardial Infarction (STEMI). STEMI has a high mortality risk, which can be reduced by reperfusion of the myocardium. However, injury can occur, which in animals leads to apoptosis – the end effector of which is p17 caspase 3.

Using p17 caspase 3 antibody ELISA techniques, Agosto was able to show a four-fold increase of p17 caspase 3 levels in patients undergoing treatment for STEMI, compared to healthy controls.

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Are ABCA1 Mutations a Risk Factor for Strokes?

Monday, February 21st, 2011

The ATP Binding Cassette Transporter (ABCA1) gene encodes the cholesterol regulatory efflux protein, which plays a key role in lipid metabolism. ABCA1 antibody products are an important part of any antibody catalog covering atherosclerosis disease research.

Atherosclerosis (narrowing of the arteries) is characterized by a build-up of fatty plaques, containing cholesterol, causing arteries to narrow. These plaques can then become ulcerated, causing blood clots to form. If this occurs in the carotid arteries the clots can travel to the brain, causing a stroke. In the general population, low plasma HDLC levels are well documented to increase the risk of coronary heart disease.

ABCA1 antibody studies in animal models have shown ABCA1 gene mutations increase the risk of atherosclerosis. Researchers also discovered that oxidation of LDL in the cells of the arterial wall is modulated by ABCA1. In atherosclerotic plaques, ABCA1 upregulation occurred, suggesting a link between ABCA1 expression and the formation of plaques. Results also suggested ABCA1 polymorphisms can affect lipid profiles, and that ABCA1 may play an essential role in regulating ApoA-I and ApoE levels in the brain.

In humans, a 2005 Hungarian study of stroke patients suggested two ABCA1 polymorphisms which may offer protection from strokes. However, a similar study by Pasdar et al in 2007 showed no significant effect – positive or negative – in four ABCA1polymorphisms, although they reported a change in serum lipid levels.

In 2009, P. Isoviita et al conducted CD36 and ABCA1 antibody assay studies on carotid plaques (CPs). The results suggested that an imbalance between lipid efflux and influx, represented by CD36 and ABCA1 levels, could lead to carotid plaque build-up, intraplaque hemorrhages and increased stroke risk. We at Novus Biologicals have an extensive antibody catalogue covering ABCA1 antibody research.

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TNF Alpha Antibodies as Therapeutic Tools

Monday, February 14th, 2011

Tumor 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.

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The Rad51 Antibody Reveals a Canine Model for Human Breast Cancer

Friday, February 11th, 2011

Our antibody catalogue includes an extensive range of Rad51 antibody reagents. Encoded by the RAD51 gene, the Rad51 protein plays a vital role in DNA repair, interacting with several other proteins, including BRCA1 and BRCA2, to effect homologous recombination at double-strand breaks. In 2010, German Rad51 antibody studies showed Rad51 levels were significantly raised in canine metastatic tumours. In general there was significant correlation between canine and human oncogenes, suggesting a possible animal model for human breast cancer.

Double-strand breaks (DSBs) are extremely common, and are caused by a number of environmental factors including ionizing radiation, UV light and certain chemicals. They also occur naturally when genetic material is exchanged during cell division. Genetic changes of BRCA and RAD51 are known to dramatically increase the risk of breast cancer in humans. BRCA and RAD51 mutations are often found together; RAD51/BRCA binding could play a tumour-suppressive role in normal cells.

Rad51 performs an important role at DNA breakage sites, encasing the break in a protein sheath – the first stage in DSB repair. Rad51 antibody studies have shown BRCA2 regulates the process by transporting Rad51 to breakage sites. The action of BRCA1 is less clear, but it is thought to play a role in activating Rad51 following DNA damage. Rad51 antibody research is integral to developing novel therapies for human breast cancer.

Recently, R. Klopfleisch et al, of the Freie University, Berlin, identified 1,011 genes which were significantly modified in canine mammary tumours – including 265 of relevance to humans, including RAD51. This suggests a useful animal model for human research. We at Novus Biologicals have an extensive antibody catalog covering this area.

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The Hif-1 Alpha Antibody and Prostate Cancer Research

Monday, February 7th, 2011

The Hypoxia-inducible Factor 1 (HIF1) protein is a heterodimeric transcription factor which plays an important role in mammalian oxygen homeostasis in conditions of hypoxia, or low oxygen concentration. HIF-1 alpha antibody reagents are widely used in disease research, as hypoxia is known to contribute to many diseases including cancer, pulmonary hypertension and congenital heart disease. We at Novus Biologicals are one of the leading antibody suppliers of HIF-1 products.

HIF-1 alpha is one of two subunits forming the HIF-1 heterodimer. Under normal conditions it undergoes continual translation, ubiquitination and degradation, but in hypoxic conditions degradation ceases while transcription increases. Expression of HIF-1 alpha is regulated by several enzymes, including the E3 ubiquitin-protein ligase Siah2.

HIF-1 regulates a number of genes known to be over expressed in certain tumours. Recently J.Qi et al, of the Sanford-Burnham Medical Research Institute, recruited the HIF-1 alpha antibody in a research study which threw light on the role of HIF-1 and Siah2 in the formation of the neuroendocrine (NE) phenotype and aggressive NE prostate tumours. The study used the TRAMP prostate cancer mouse model.

It was seen that prostate tumour formation was suppressed in those mice deficient in Siah2. In normal mice, HIF-1alpha interacted with FoxA2, a transcription factor widely expressed in neuroendocrine tissue, promoting recruitment of the transcriptional co-activator p300. This selectively activated the HIF-regulated genes, Sox9, Hes6, and Jmjd1a. These proteins are highly expressed in metastatic prostate adenocarcinomas (PCas), PCa metastasis, NE tumour formation and the NE phenotype – which is seen in around 30% of NE tumours.

We are one of the leading antibody suppliers for research studies of this kind.

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HIF-1 Beta Antibody Studies and Developments in Hypoxia Research

Monday, January 31st, 2011

We at Novus Biologicals have a large HIF-1 (Hypoxia Inducible Factor-1) antibody catalogue, with twenty HIF-1 beta antibody products specifically targeted to the beta subunit of HIF-1, a heterodimer which is known to contribute to many human diseases arising from changes in oxygen homeostasis.

HIF-1 is a transcription factor and key mediator of homeostasis triggered by hypoxia. It drives the transcription of more than 60 genes concerned with anaerobic metabolism, cell survival, cytokine production, the immune reaction, vascularisation and all areas of tissue homeostasis. It is also a key hypoxic regulator of embryonic vascular development.

HIF-1 alpha and HIF-1 beta antibody studies have shown that the subunits of HIF-1 are dissociated in normoxia. The beta subunit resides in the nucleus while the alpha subunit is cytoplasmic and rapidly ubiquitinised. In conditions of hypoxia, HIF-1 alpha ubiquitinisation ceases, allowing it to accumulate in the cytoplasm and relocate to the nucleus, leading to formation of the active HIF-1 heterodimer with HIF-1 beta. This initiates transcription of VEGF, and stabilisation of mRNA.

HIF-1 alpha and HIF-1 beta antibody products are widely used in the study of human disease. Prolonged hypoxia can lead to sepsis, circulatory collapse and rapid organ failure, and is a major contributor to many human diseases, including cerebral and myocardial ischemia, chronic obstructive pulmonary disease, pulmonary hypertension, congenital heart disease and cancer.

The HIF-1 beta antibody products in our antibody catalog are widely used in cancer research, as HIF-1 heterodimer activation is commonly seen in tumour formation, and is associated with angiogenesis via VEGF expression. Recent HIF-1 beta antibody studies by Zhang and others have suggested inhibition of HIF-1 as a possible route for cancer therapy.

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