Sequential release of nitric oxide, zinc, and superoxide in hypoglycemic neuronal death.

Oxidative stress and zinc release are both known to contribute to neuronal death after hypoglycemia; however, the cause-effect relationships between these events are not established. Here we found, using a rat model of profound hypoglycemia, that the neuronal zinc release and translocation that occur immediately after hypoglycemia are prevented by the nitric oxide synthase inhibitor 7-nitroindazole but not by overexpression of superoxide dismutase-1 (SOD-1). However, overexpression of SOD-1 prevented activation of poly(ADP-ribose) polymerase-1 (PARP-1) and neuronal death, suggesting that zinc release is upstream of superoxide production.

Hypoglycemic neuronal death is triggered by glucose reperfusion and activation of neuronal NADPH oxidase.

Hypoglycemic coma and brain injury are potential complications of insulin therapy. Certain neurons in the hippocampus and cerebral cortex are uniquely vulnerable to hypoglycemic cell death, and oxidative stress is a key event in this cell death process. Here we show that hypoglycemia-induced oxidative stress and neuronal death are attributable primarily to the activation of neuronal NADPH oxidase during glucose reperfusion.

Human serum albumin and its N-terminal tetrapeptide (DAHK) block oxidant-induced neuronal death.

Background And Purpose: Studies using animal models of stroke have shown that human serum albumin (HSA) significantly ameliorates cerebral ischemic injury after both transient and permanent ischemia, even when administered after the onset of ischemia or reperfusion. The mechanism of this effect remains uncertain, and prior studies suggest both indirect hemodynamic and direct cytoprotective effects. HSA is a potent antioxidant, in part because of its strong copper-binding capacity.

Hypoglycemic neuronal death and cognitive impairment are prevented by poly(ADP-ribose) polymerase inhibitors administered after hypoglycemia.

Severe hypoglycemia causes neuronal death and cognitive impairment. Evidence suggests that hypoglycemic neuronal death involves excitotoxicity and DNA damage. Poly(ADP-ribose) polymerase-1 (PARP-1) normally functions in DNA repair, but promotes cell death when extensively activated by DNA damage.

The carboxyl-terminal sequence of the human secretory mucin, MUC6. Analysis Of the primary amino acid sequence.

The distribution of MUC6 suggests that its primary function is protection of vulnerable epithelial surfaces from damaging effects of constant exposure to a wide range of endogenous caustic or proteolytic agents. A combination of genomic, cDNA. and 3' rapid amplification of cDNA ends techniques was used to isolate the carboxyl-terminal end of MUC6.

Human gastric mucin. Identification of a unique species by expression cloning.

Gastric mucin is a large glycoprotein which is thought to play a major role in the protection of the gastrointestinal tract from acid, proteases, pathogenic microorganisms, and mechanical trauma. In this paper we describe the isolation by expression cloning and characterization of cDNAs which code for human gastric mucin. The cDNA sequence is characterized by a tandem repeat region whose individual repeat unit is 507 base pairs (169 amino acids) long.

Heterogeneity of mucin gene expression in normal and neoplastic tissues.

To determine the relative expression of distinct mucin genes in normal and neoplastic tissue, antibodies and cDNA probes that recognize the core tandem repeat sequences of membrane-bound (MUC1) and secreted (MUC2 and MUC3) mucins were used for immunohistochemical and RNA Northern and slot-blot analysis. MUC1 mRNA was detected in all epithelial tissues tested. MUC1 core peptide, recognized by monoclonal antibodies 139H2 and DF3, was highly expressed on apical membranes of bronchus, breast, salivary gland, pancreas, prostate, and uterus, and was sparsely expressed in gastric surface cells, gallbladder, small intestine, and colonic epithelium.

Effect of somatostatin on adenylate cyclase activity in normal and neoplastic thyroid tissue.

Thyroid stimulating hormone (TSH) and other substances increase adenylate cyclase (AC) activity and growth of normal and neoplastic thyroid tissue. Factors that inhibit cAMP may provide targeted therapy to tumors dependent on cAMP for growth. Somatostatin has been reported to inhibit the growth of gastrinomas and carcinoid tumors.

Expression of dipeptidyl aminopeptidase IV during enterocytic differentiation of human colon cancer (Caco-2) cells.

The human colon cancer cell line Caco-2 spontaneously differentiates to an enterocyte-like cell after confluence under standard culture conditions. This is characterized by polarization of the cell monolayer with the appearance of tight junctions, a brush border membrane and expression of brush-border-membrane-associated hydrolases. Studies have shown that differentiated Caco-2 cells express relatively high levels of dipeptidyl aminopeptidase IV (DPP IV) when compared with other enzymes.

Biosynthesis of alkaline phosphatase during differentiation of the human colon cancer cell line Caco-2.

The human colon cancer cell line Caco-2 undergoes spontaneous enterocytic differentiation during growth and expresses a number of brush-border membrane-associated hydrolases typical of a differentiated phenotype. Among these is the enzyme alkaline phosphatase, which is frequently used as a marker of cell differentiation in colon cancer cells. Since the biochemical processes regulating the expression of alkaline phosphatase during cell differentiation are only poorly understood, we examined the biosynthesis and processing of alkaline phosphatases in undifferentiated (0-day confluent) and differentiated (14-day confluent) Caco-2 cells.

Epidermal growth factor receptors in parathyroid tumors.

Hyperparathyroidism is caused by parathyroid adenomas, hyperplastic parathyroid glands, or rarely parathyroid carcinoma. Membrane receptors to epidermal growth factor (EGF), a growth-stimulating polypeptide, have been shown in other endocrine tissues such as thyroid, breast, and ovary, but not in parathyroid glands. Therefore we studied abnormal parathyroid glands from fourteen patients for the presence of EGF receptors.

Mineral metabolism of rats fed moderate levels of various aluminum compounds for short periods of time.

The effects of ingesting moderate levels of aluminum (5-272 micrograms Al/g diet) were assessed in two short-term (18-d) studies with rats. Rats were fed diets that contained no added aluminum or aluminum lactate, aluminum palmitate, aluminum phosphate or aluminum hydroxide in either reagent grade or desiccated gel forms. The average concentrations of aluminum in the tibias of rats fed 261-272 micrograms Al/g diet were 13.

Epidermal growth factor receptors in normal and neoplastic thyroid tissue.

Epidermal growth factor (EGF) stimulates DNA synthesis and proliferation of thyroid cells in culture and may have an important role in the regulation of normal and neoplastic thyroid cell growth. We therefore studied paired normal and neoplastic thyroid tissue from eight patients for the presence of EGF receptors using a radioreceptor assay. 125I EGF binds to a particulate membrane fraction from both normal and neoplastic thyroid tissue with high affinity (dissociation constant ranged from 0.

Prostaglandin prevents alterations in DNA, RNA, and protein in damaged gastric mucosa.

Fasted rats were given either 16,16-dimethyl-PGE2 (dmPGE2) (1 microgram/kg) or normal saline subcutaneously followed by the oral administration of 1 ml of 100% ethanol or saline 30 min later. At 1, 3, 6, and 24 hr later, animals were sacrificed, their stomachs examined for necrotic ulcerations, and the incorporation of [3H]thymidine into DNA as well as tissue levels of DNA, RNA, and protein content of glandular mucosa determined. Compared with control animals, severe ulcerations of 70-80% of the glandular mucosa were observed in rats given 100% ethanol at all time periods.

Serum zinc levels in lung cancer patients.

Serum zinc concentrations were determined in 26 extensive squamous cell lung cancer patients and were tested for correlations with survival, response to therapy, nutritional status indices, and various host defense characteristics. Subnormal serum zinc levels were found in 24 of the 26 patients. The mean serum zinc concentration was 43.

Comparison of four purified extracellular 1,4-beta-D-glucan cellobiohydrolase enzymes from Trichoderma viride.

Four electrophoretically distinct 1,4-beta-D-glucan cellobiohydrolase enzymes (exo-cellobiohydrolase, EC 3.2.1.

Structural characterization of a glycoprotein cellulase, 1,4-beta-D-glucan cellobiohydrolase C from Trichoderma viride.

A glycoprotein enzyme, 1,4-beta-D-glucan cellobiohycrolase (EC 3.2.1.