Biomaterial Database

Characterization of the neurotrophic interaction between nerve growth factor and secreted alpha-amyloid precursor protein. 2001

J J Luo, and M S Wallace, and D B Hawver, and J W Kusiak, and W C Wallace

Laboratory of Cellular and Molecular Biology, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.

The expression and secretion of amyloid precursor protein (beta APP) is increased in rat cerebral cortices that have been denervated by subcortical lesions of the nucleus basalis of Meynert. The physiological role of the secreted beta APP in response to this injury has not been established. We have previously shown that secreted beta APP produced by alpha-secretase activity (sAPP(alpha)) potentiates the neuritogenic activity of nerve growth factor (NGF) in vitro on naive PC12 cells. In this investigation, we have further characterized the neurotrophic interaction of NGF and sAPP(alpha) using differentiated PC12 cells and rat primary cortical neurons. NGF required the expression of beta APP to maintain a neuronal phenotype. Reduction of endogenous beta APP expression by introduction of antisense oligonucleotides in the presence of NGF resulted in loss of neurites from differentiated PC12 cells but no apparent cell death. Addition of exogenous sAPP(alpha) (60--200 pM) potentiated the protective activity of NGF in serum-deprived differentiated PC12 cells as determined by retention of neurites and cell viability. In addition, exogenous sAPP(alpha) increased neuron viability in both short-term (3 days) cortical neuron cultures grown in the absence of serum and in long-term (9 days) cultures grown with serum. Disruption of the insulin signaling pathway by reduction of IRS-1 expression inhibited the ability of sAPP(alpha) to potentiate neurotrophic activity. These observations suggest that sAPP(alpha) acts as an injury-induced neurotrophic factor that interacts with NGF to enhance neuronal viability using the insulin signaling pathway.

UI	MeSH Term	Description	Entries
D007328	Insulin	A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).	Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D009930	Organic Chemicals	A broad class of substances containing carbon and its derivatives. Many of these chemicals will frequently contain hydrogen with or without oxygen, nitrogen, sulfur, phosphorus, and other elements. They exist in either carbon chain or carbon ring form.	Organic Chemical,Chemical, Organic,Chemicals, Organic
D010450	Endopeptidases	A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.	Endopeptidase,Peptide Peptidohydrolases
D010641	Phenotype	The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.	Phenotypes
D010750	Phosphoproteins		Phosphoprotein
D002417	Cattle	Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.	Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D002454	Cell Differentiation	Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.	Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002540	Cerebral Cortex	The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions.	Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
D003470	Culture Media	Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as AGAR or GELATIN.	Media, Culture
D004357	Drug Synergism	The action of a drug in promoting or enhancing the effectiveness of another drug.	Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug