Novus Biologicals | Antibody News

Diabetic nephropathy (DN) is one of the leading complications resulting from chronic diabetes. It manifests as progressive renal failure caused by mesangial cell hyperplasia and fibrosis, and is one of the leading causes of terminal kidney disease (1). While the etiology is complex, an imbalance between pro- and anti-oxidant pathways in the kidney leading to an excess accumulation of reactive oxygen species (ROS) is believed to contribute in large part to the development of DN. The primary source of ROS in the context of DN are NAD(P)H oxidases, a family of enzymes that facilitate respiratory bursts in phagocytic cells and participate in ROS-mediated signaling in a variety of other cell types (2). In the renal environment, ROS such as superoxide anion and hydrogen peroxide are generated as intermediates in redox reactions but are quickly neutralized by enzymes such as superoxide dismutase and catalase.

Recent antibody studies have indicated that high glucose levels up-regulate NAD(P)H oxidases, altering oxidant homeostasis and contributing to vascular dysfunction observed in DN.  Sechi, et al. demonstrated that anti-oxidant enzyme activity was increased in the kidneys of streptozotocine-induced diabetic rats (3), and numerous other studies associate a rise in ROS with susceptibility to DN secondary to diabetes. Podocytes are especially vulnerable to the effects of high glucose levels; Piwkowska et al confirmed the pivotal role of the NAD(P)H oxidase, Nox4, in promoting damage characteristic of DN (4). This is not surprising, as Nox4 antibody research have suggested NOX4 is a master regulator of oxidative stress in previous studies, and is known to be constitutively expressed in the kidney (4,5). In addition to podocytes, mesangial cells show the pathological features of DN and elevated NOX4 activity subsequent to hyperglycemia (4). Considerable data has been amassed solidifying the potential of NOX4 as a therapeutic target for DN, and interesting evidence has emerged suggesting that herbal remedies may help treat DN by interfering with NOX4 (6).

Novus offers high quality NOX4 antibodies, guaranteed for most species and immunological applications. NOX4 antibodies are supplied in a variety of DyLight fluorescent conjugates and excellent staining data is available for each. Please contact our technical support department with any questions or for additional information.

1. Ren G, Huynh C, Bijian K, Cybulsky A.  2008.  Role of apoptosis signal-regulating kinase 1 in complement-mediated glomerular epithelial cell injury.  Mol Immunol.  45:2236-2246.
2. Touyz R, Briones A.  2011.  Reactive oxygen species and vascular biology: implications in human hypertension.  Hypertension Research  34, 5-14.
3. Sechi L, Ceriello A, Griffin CA, Catena C, Anstad P, Schambelan M, Bartoli E.  1997.  Renal antioxidant enzyme mRNA levels are increased in rats with experimental diabetes mellitus.  Diabetologia  40:23-29.
4. Piwkowska T, Rogacka D, Audzeyenka I, Jankowski M, Angielski S.  2011.  High Glucose Concentration Affects the Oxidant-Antioxidant Balance in Cultured Mouse Podocytes.  J Biol Chem  112:1661-1672.
5. Jeong S, Kim S, Kwon T, YuK, Kim S.  2011.  Schizandrin prevents damage of murine mesangial cells via blocking NAD(P)H oxidase-induced ROS signaling in high glucose.  Food and Chemical Toxicology  (article in press).
6. Morgensen C.  2003.  Microalbuminuria and hypertension with focus on type 1 and type 2 diabetes.  J Intern Med  254:45-66.
7. Yi F, Zhang A, Li N, Muh R, Fillet M, Renert A, Li P.  Inhibition of ceramide-redox signaling pathway blocks glomerular injury in hyperhomocysteinemic rats. Kidney Int  70, 88-96. 2006.

P53 is a stress-activated transcription factor, encoded by the TP53 gene. An important tumor suppressor, the protein mediates cellular growth and proliferation, regulating proteins involved in the stress-response. In p53 antibody studies, the protein has been shown to play an important role in the cellular response to DNA damage. Activation of p53 in response to stress stimuli may promote either cell cycle arrest followed by DNA repair, or apoptosis. We at Novus Biologicals are major antibody suppliers of p53 research products.

TP53 is one of the most widely mutated oncogenes, being linked to a large number of carcinomas. It is estimated around 50% of all tumors feature genetically modified or inactivated p53. Not surprisingly, the p53 antibody is widely used in cancer research. Although the function of the protein is to arrest the cell cycle in response to cellular stress, studies have shown that in its mutated form P53 may act as both a tumour suppressor and promoter.

Numerous studies have shown the p53 transcription factor plays transcriptional, posttranscriptional, and posttranslational roles, targeting multiple genes and microRNAs connected to a wide range of cellular activities apart from apoptosis and regulation of cell cycle arrest. In vivo and in vitro studies have shown p53 to be phosphorylated at multiple sites, by a number of different protein kinases, leading to an extensive database of p53 antibody products. Novus is able to supply conjugated and non-conjugated p53 antibody reagents targeting both the entire protein and specific epitopes, suitable for use in a wide range of normal and cancer cell lines.

Heat Shock Proteins (HSPs) are a ubiquitous group of molecular chaperone proteins that have evolved unique mechanisms, within their host cells, to facilitate survival in hostile environments such as heat, oxidative (hypoxia), pH and cold. Under permissive conditions, the proteins are constitutively expressed and many have important or essential roles in the cell, including the protein export, regulation, turnover and the prevention of protein aggregation.  There are many classes of HSPs, which are divided into 5 families on the basis of their apparent molecular size and sequence homology:  Hsp100, Hsp90, Hsp70, Hsp60 and the small HSP’s (15-30kDa).

HSP100 proteins are amongst the most conserved within their chaperone family. The most characterised member within this group is the homohexameric toroid protein found in yeast, HSP104. Their major role is thought to be targeting mis-folded proteins and passing them through their central cavity, thus allowing the mis-folded protein to refold.

HSP90 has five isoforms to date including the cytoplasmic HSP90a and HSP90b. The HSP90’s are thought to regulate more than 200 proteins, covering many cellular processes within the cell. The list is constantly being updated however the most characterised so far are: HIF-1a, SRC, HER2, EGFR, BRAF, AKT, MET, VEGFR and FLT3.

Human cells contain several HSP70 family members and play many roles within the cell. Interestingly, they have been found specifically affecting the intrinsic and extrinsic pathway of apoptosis, by inhibiting the apoptotic mediator protein, Bax translocation. Jointly with its co-chaperone HSP40, HSP70 also blocks TNF-induced apoptosis and HSP70 also directly interacts with Apaf-1, consequently inhibiting the recruitment of procaspase-9 to the apoptosome and the resulting caspase-3 activation.

The HSP60 family of proteins generally comprise of a 7 or 8 sub-units, in a double ringed conformation. The family exhibit ATPase activity and it is thought that the binding and hydrolysis of ATP is essential for the reaction cycle and the result binding and release of partially or mis-folded substrate proteins.

The small HSPs are the most diverse and least studied family and have a low overall identity between fellow members of 20-30% and this is mainly found in the C-terminal half of the proteins. Alpha A Crystallin and Alpha B Crystallin constitute a large percentage of the protein found in the vertebrate eye lenses, function as chaperones by preventing protein aggregation and refolding.