Search results

Wheat Gliadin and related gluten components from barley, rye and possibly oats can cause an abnormal immune response called Celiac disease which is a chronic gastrointestinal disorder. Celiac disease characteristics are flattening of the jejunal mucosa and intestinal lesions of variable severity in hereditarily inclined individuals. Even though Celiac disease is not a classic autoimmune disease it is related to anti-tissue transglutaminase antibodies and gliadin antibodies tests are most recommended in screening populations at risk for CD and other gluten-sensitive enteropathies. In the past, serologic tests for gliadin antibodies usually were not very precise and were not enough for accurate diagnosis due to missing deamidated epitopes within the authentic gliadin fraction traditionally used in diagnostic test kits. ProSpec's deamidated Gliadin isoform matches to the deamidated neo-epitopes, which in the natural antigen are formed by transglutaminase-mediated glutamine side chain deamidation.

Polypeptide hormones secreted by the parathyroid glands, which promote release of calcium from bone to extracellular fluid by activating osteoblasts and inhibiting osteoclasts, indirectly promote increased intestinal absorption of calcium, and promote renal tubular reabsorption of calcium and increased renal excretion of phosphates. It is a major regulator of bone metabolism. Secretion of parathyroid hormone increases when the level of calcium in the extracellular fluid is low. Its action is opposed by calcitonin.
PTH (7-34), which is a PTH/PTHrP receptor antagonist, can stimulate hair growth and epidermal proliferation in mice.

SNCA or Alpha-synuclein is a protein with undisclosed function that mainly concentrated in the brain tissue, mainly in the tips of the neurons in the presynaptic terminals. Almost 1% of the proteins in the brain tissues are synucleins. The protein is located mainly in the hippocampus, thalamus, cerebellum & neocortex. Smaller amounts of the SNCA protein can be found in the neuroglial cells. The MITF protein regulates the SNCA expression in melanocytic cells.

PPIH is a part of the peptidyl-prolyl cis-trans isomerase (PPIase) family. PPIases catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and increase protein folding. PPIH enzyme is a precise factor of the complex that comprises pre-mRNA processing factors PRPF3, PRPF4, and PRPF18, as well as U4/U5/U6 tri-snRNP. PPIH possess PPIase activity and acts as a protein chaperone that mediates the interactions between different proteins inside the spliceosome.

Natriuretic Peptide Precursor B acts as a cardiac hormone with a variety of biological actions including natriuresis, diuresis, vasorelaxation, and inhibition of renin and aldosterone secretion. It is thought to play a key role in cardiovascular homeostasis. Helps restore the body's salt and water balance. Improves heart function.

Collagen, a major component of the extracellular matrix, is a fibrous protein that provides tensile strength to tissues giving them structural integrity. Collagen and its derivative, gelatin, have been widely used in medical, pharmaceutical and consumer products for more than 100 years. The supply of these materials, created from animal remains, is both abundant and inexpensive. However, most formulations are not highly purified and have the potential to cause an inflammatory reaction in some product users. In addition, concerns have been raised over the last several years about the potential for contamination of bovine products with the agent that causes mad cow disease and its human variant, Creutzfeldt-Jakob Disease. Animal collagens are subject to extensive modifications that continue over the life of the molecule in the extracellular space. These differences influence both the extractability of collagens from tissue and the biophysical characteristics of these collagens. As a result, collagens isolated from tissues exhibit significant lot-to-lot variability and, as bulk materials, are often analytically intractable. Products that contain animal-derived collagen can induce potentially harmful inflammatory or immune responses in humans and pose risk of contamination with viruses or prions, potentially life-threatening pathogens. Recombinant collagens are essentially identical to the native collagen protein thereby reducing the risk of inflammation, immune response, and disease as compared to animal-sourced collagen.

Activins are homodimers or heterodimers of the different β subunit isoforms, part of the TGFβ family. Mature Activin A has two 116 amino acids residues βA subunits (βA-βA). Activin displays an extensive variety of biological activities, including mesoderm induction, neural cell differentiation, bone remodelling, haematopoiesis, and reproductive physiology. Activins takes part in the production and regulation of hormones such as FSH, LH, GnRH and ACTH. Cells that are identified to express Activin A include fibroblasts, endothelial cells, hepatocytes, vascular smooth muscle cells, macrophages, keratinocytes, osteoclasts, bone marrow monocytes, prostatic epithelium, neurons, chondrocytes, osteoblasts, Leydig cells, Sertoli cells, and ovarian granulosa cells.

The somatomedins, or insulin-like growth factors (IGFs), comprise a family of peptides that takes part in mammalian growth and development. IGF1 mediates various growth-promoting effects of growth hormone (GH; MIM 139250). Early studies showed that growth hormone did not directly stimulate the incorporation of sulfate into cartilage, but rather acted through a serum factor, termed 'sulfation factor,' which later became known as 'somatomedin' (Daughaday et al., 1972). 3 main somatomedins have been characterized: somatomedin C (IGF1), somatomedin A (IGF2; MIM 147470), and somatomedin B (MIM 193190) (Rotwein, 1986; Rosenfeld, 2003).

Cathepsin D is synthesized as a 54kDa precursor, which is proteolytically processed to an intermediate 48kDa single chain, which matures into more stable 34kDa and 14kDa two chain form. It is an estrogen-regulated lysosomal protease that has been suggested to facilitate cancer cell migration and invasion by digesting the basement membrane, extracellular matrix, and xonnective tissue. Because of its mitogenic and proteolytic activities, it has been implicated as a prognostic marker in many tumor types. Cathepsin D is expressed in epithelial cells as well as in macrophages.

HB-EGF is an EGF related growth factor which signals via the EGF receptor, and stimulates the proliferation of SMC (smooth muscle cells), fibroblasts, epithelial cells and keratinocytes. HB-EGF is expressed in various cell types and tissues, including vascular endothelial cells and SMC, macrophages, skeletal muscle, keratinocytes and particular tumor cells. HB-EGF’s ability to explicitly bind HPR sulfate proteoglycans is dissimilar from other EGF-like molecules, and might be related to the enhanced mitogenic activity, relative to EGF, that HB-EGF exerts on smooth muscle cells.

Interleukin-8 (IL-8) is a chemokine produced by macrophages and other cell types such as epithelial cells. It is also synthesized by endothelial cells, which store IL-8 in their storage vesicles, the Weibel-Palade bodies. When first encountering an antigen, the primary cells to encounter it are the macrophages who phagocytose the particle. Upon processing, they release chemokines to signal other immune cells to come in to the site of inflammation. IL-8 is one such chemokine. It serves as a chemical signal that attracts neutrophils at the site of inflammation, and therefore is also known as Neutrophil Chemotactic Factor.

Connective Tissue Growth Factor belongs to the CCN family of proteins. The CCN family presently consists of six members in human also known as: Cyr61 (Cystein rich 61), CTGF (Connective Tissue Growth Factor), Nov (Nephroblastoma Overexpressed gene), WISP-1, 2 and 3 (Wnt-1 Induced Secreted Proteins). The CCN genes encode secreted proteins associated with the Extracellular Matrix (ECM) and cell membrane. CCN proteins are matricellular proteins which are involved in the regulation of various cellular functions including: proliferation, differentiation, survival, adhesion and migration. They are expressed in derivatives of the three embryonic sheets and are implicated in the development of kidney, nervous system, muscle, bone marrow, cartilage and bone. During adulthood, they are implicated in wound healing, bone fracture repair, and pathologies such as: fibrosis, vascular ailments and tumorigenesis.
Full length secreted CCN proteins can show an antiproliferative activity, whereas truncated isoforms are likely to stimulate proliferation and behave as oncogenes. The full length protein consists of four modulesModule I shares partial identity with the N-terminal part of the Insulin-like Growth Factor Binding Proteins (IGFBPs).
Module II includes a stretch of 70amino acid residues – which shares sequence identity with the Von Willebrand Factor Type C repeat (VWC).
Module III contains sequences sharing identity with the Thrombospondin type 1 repeat (TSP1) (WSXCSXXCG), which is thought to be implicated in the binding of sulfated glycoconjugates and to be important for cell adhesion. Module IV, also designated CT, is encoded by exon5. It is the leasts conserved one of the four domains at the level of nucleotide sequence, but it appears to be critical for several of the biological functions attributed to the CCN proteins. Module IV resembles the CT domain of several extracellular protein including, Von Willebrand's factor and mucins. Sequence similarities to heparin-binding motifs are also found within this domain. Proteolysis of the secreted full-length CCN proteins that has been reported in the case of CCN2 and CCN3 might result in the production of CCN-derived peptides with high affinity for ligands that full-length CNN proteins bind only poorly. Amino-truncated CCN2 isoforms were biologically active whereas no specific biological activity has been attributed to the truncated CCN3. Although the molecular processes underlying the production of these secreted isoforms is presently unknown, it is important to note that proteolysis occur at the same amino acid residues in both CCN2 and CCN3. An elevated expression of CCN2 has also been detected by Northern blotting in human invasive mammary ductal carcinomas, dermatofibromas, pyogenic granuloma, endothelial cells of angiolipomas and angioleiomyomas, and in pancreatic tumors. A study performed with chondrosarcomas representative of various histological grades established that CCN2 expression was closely correlated with increasing levels of malignancy. In agreement with CCN2 playing a role in brain tumor angiogenesis, immunocytochemistry studies indicated that both glioblastoma tumor cells and proliferating endothelial cells stained positive for CCN2. In astrocytomas, CCN2 expression was particularly elevated in high grade tumors, with a marked effect of CCN2 on cell proliferation. Downregulation of CCN2 expression in these cells was associated with a growth arrest at the G1/S transition while over-expression of CCN2 induced a two-fold increase of the number of cells in the G1 phase. Gene profiling analysis allowed to identify a set of about 50 genes whose expression might account for the proliferative activity of CCN2 in these cells.
CCN2 was seen in a higher proportion of mononuclear cells of patients with acute lymphoblastic leukemia.

C-JUN is a gene which, in combination with c-Fos, forms the AP-1early response transcription factor. C-JUN is activated by the JNKpathway. C-JUN is the putative transforming gene of avian sarcoma virus 17. C-JUN is a protein which is highly similar to the viral protein, and which interacts directly with specific target DNA sequences to regulate gene expression. The C-JUN gene is intronless and is mapped to 1p32-p31, a chromosomal region involved in both translocations and deletions in human malignancies.

Cystatins are a superfamily of cysteine proteinase inhibitors found in both plants and animals. They comprise a group of proteinase inhibitors, widely distributed in tissues and body fluids, and form tight complexes with cysteine proteases such as cathepsin B, H, L and S. Cystatin C, a secreted molecule of this family, is of interest from biochemical, medicine and evolutionary points of view. Cystatin C, with molecular weight of 13260 Da, is composed of 120 amino acids, lacks carbohydrate and has two disulfide bridges located near the carboxyl terminus. Cystatin C is increased in patients with malignant diseases, and is related to the insufficiency of renal function and appears to be a better marker than creatinine. On the other hand, low levels of cystatin C involve cause the breakdown of the elastic laminae and, subsequently, the atherosclerosis and abdominal aortic aneurysm.

S100A8 is a part of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a broad range of cells, and participate in the regulation of cellular processes such as cell cycle progression and differentiation. S100A8 plays a role in the inhibition of casein kinase and as a cytokine. S100A8 altered expression is related with cystic fibrosis disease. S100A8 is a calcium-binding protein that has antimicrobial activity against bacteria and fungi.S100A8 is crucial for resistance towards invasion by pathogenic bacteria. S100A8 up-regulates transcription of genes that are under the control of NF-kappa-B. S100A8 plays a role in the development of endotoxic shock in response to bacterial lipopolysaccharide. S100A8 endorses tubulin polymerization and promotes phagocyte migration and infiltration of granulocytes at sites of wounding. S100A8 takes part as a pro-inflammatory mediator in acute and chronic inflammation and up-regulates the release of IL8 and cell-surface expression of ICAM1.

ACTA2 is a member of the actin family of proteins, an extremely conserved family of proteins which takes part in cell motility, structure and integrity. Three types of actin isoforms are known: Alpha, beta and gamma. Alpha actins are a main factor of the contractile mechanism, and beta and gamma take part in the regulation of cell motility. ACTA2 is an alpha actin which is located in skeletal muscle. Mutations in ACTA2 cause aortic aneurysm familial thoracic type 6. Various alternatively spliced variants, encoding the same protein were identified.

PPIases catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and accelerate the folding of proteins. Cyclophilin-A is a cyclosporin binding-protein and may play a role in cyclosporin A-mediated immunosuppression. Cyclophilin-A can also interact with several HIV proteins, including p55 gag, Vpr, and capsid protein, and has been shown to be necessary for the formation of infectious HIV virions. Multiple pseudogenes that map to different chromosomes have been reported.

DBH catalyzes the chemical reaction. DBH is an oxidoreductase which belongs to the copper type II, ascorbate-dependent monooxygenase family, in particular those performing on paired donors, with O2 as oxidant and incorporation or reduction of oxygen. The oxygen incorporated can not be derived from O2 with reduced ascorbate as one donor, as well as incorporation of one ato of oxygen into the other donor.

SEMA3C, also known as Semaphorin 3C, is a member of the semaphorin family 3 that are grouped into 8 major classes based on phylogenetic tree analyses and structure. Class 3 have an important function after traumatic central nervous system injuries. SEMA3C regulates neuronal and non-neuronal cells associated with the traumatic injury due to their presence in the scar tissue. SEMA3C is expressed in all somatic motor neurons, in cardiac neural crest cells during development and in lung buds. The SEMA3C functions are mediated through binding to the Plexin-D1 and Neuropilin 1 or Neuropilin 2 coreceptor complex. SEMA3C activates integrins in certain cells, so besides its repulsive activities, it also acts as a chemoattractant.

HPCAL1, participates in neuron-specific calcium-binding proteins family found in the retina and brain. HPCAL1 is extremely comparable to human hippocalcin protein and almost equal to the rat and mouse hippocalcin like-1 proteins. HPCAL1 takes part in the calcium-dependent regulation of rhodopsin phosphorylation and can have importance in neuronal signalling in the central nervous system.

EFNA1 belongs to the ephrin (EPH) family. The EPH subfamily is the biggest group of receptor protein kinases and they take part in vital nervous system function and development.

Betaine-Homocysteine Methyltransferase 2 (BHMT2) is involved in the regulation of homocysteine metabolism. Homocysteine is a sulfur-containing amino acid which has a key role in methylation reactions. Transfer of the methyl group from betaine to homocysteine generates methionine, which donates the methyl group to methylate DNA, proteins, lipids, and other intracellular metabolites. BHMT2 is one of two methyl transferases which can catalyze the transfer of the methyl group from betaine to homocysteine. BHMT2 converts homocysteine to methionine using S-methylmethionine (SMM) as a methyl donor. Homocysteine metabolism anomalies are implicated in disorders varying from vascular disease to neural tube birth defects such as spina bifida.