Generation of reactive oxygen species by mitochondrial complex I: implications in neurodegeneration.

Mitochondrial Complex I [NADH Coenzyme Q (CoQ) oxidoreductase] is the least understood of respiratory complexes. In this review we emphasize some novel findings on this enzyme that are of relevance to the pathogenesis of neurodegenerative diseases. Besides CoQ, also oxygen may be an electron acceptor from the enzyme, with generation of superoxide radical in the mitochondrial matrix.

Characterization of highly toxic type 2 ribosome-inactivating proteins from Adenia lanceolata and Adenia stenodactyla (Passifloraceae).

From the caudices of the Passifloraceae Adenia lanceolata and A. stenodactyla, two lectins called lanceolin and stenodactylin, respectively, were purified by affinity chromatography on CL Sepharose 6B. The lectins are glycoproteins with M(r) 61,243 (lanceolin) and 63,131 (stenodactylin), consisting of an enzymatic A chain linked to a larger B chain with lectin properties, with N-terminal amino acid sequences similar to that of volkensin, the toxic lectin from A.

Detection of ricin and other ribosome-inactivating proteins by an immuno-polymerase chain reaction assay.

Ribosome-inactivating proteins (RIPs) are plant proteins with enzymatic activity, classified as type 1 (single chain) or type 2 (two chains). They are identified as rRNA N-glycosidases (EC 3.2.

Clusterin up-regulation following sub-lethal oxidative stress and lipid peroxidation in human neuroblastoma cells.

Clusterin/apolipoprotein J is a multifunctional protein up-regulated during various pathophysiological states. Since oxidative stress plays an important role in brain aging, and in many neurodegenerative disorders, to further understand the mechanistic underpinnings of clusterin expression, in this study, we examined clusterin expression in human neuroblastoma cells under conditions of increased production of reactive oxygen species and lipid peroxidation. Specifically, we analyzed clusterin mRNA and protein levels in human neuroblastoma IMR-32 and SH-SY5Y cells following exposure to sub-lethal amounts of iron-ascorbate to induce an increase in reactive oxygen species generation and lipid peroxidation.

Lesions caused by ricin applied to rabbit eyes.

Purpose: Ricin, a highly potent toxin from castor beans, is a potential biological weapon that could be dispersed in the air as dust or aerosol. In these forms, ricin, besides being inhaled, could reach unprotected eyes. The present research was performed to ascertain the lesions that the toxin causes when applied to rabbit eyes.

Protein levels of glycogen synthase 3 kinase are normal in progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder characterized by pure neurofibrillary tau pathology involving mainly basal ganglia and brain stem nuclei. One of the kinases involved in tau phosphorylation is glycogen synthase 3 kinase (GSK3). In mammals GSK3 is present in two isoforms, alpha and beta regulated by phosphorylation: phosphorylation of Ser9 in GSK3beta or Ser21 in GSK3alpha leads to inactivation while phosphorylation of Tyr216 in GSK3beta or Tyr279 in GSK3alpha leads to activation.

Regulation of glycogen synthase kinase-3beta by products of lipid peroxidation in human neuroblastoma cells.

The potential role of 4-hydroxynonenal (HNE), a major product of membrane lipid peroxidation, in regulating glycogen synthase kinase-3beta (GSK3beta) activity was examined in human neuroblastoma IMR-32 cells. The inhibition of GSK3beta activity by HNE was observed by in vitro kinase assays with two substrates, the synthetic glycogen synthase peptide-2 and the human recombinant tau. GSK3beta activity is regulated by Ser9 (inhibitory) and Tyr216 (stimulatory) phosphorylation.

Up-regulation of cDK5/p35 by oxidative stress in human neuroblastoma IMR-32 cells.

Cdk5, a member of the cyclin-dependent kinase (cdk) family, is predominantly active in neurons, where its activity is tightly regulated by the binding of its neuronal activators p35 and p39. Cdk5 is implicated in regulating the proper neuronal function; a deregulation of cdk5 has been found associated with Alzheimer's disease and amyotrophic lateral sclerosis. As oxidative stress products have been seen co-localized with pathological hallmarks of neurodegenerative diseases, we studied the effect of oxidative stress on the cdk5 enzyme in human neuroblastoma IMR-32 cells.

Neuronal apoptosis is accompanied by amyloid beta-protein accumulation in the endoplasmic reticulum.

A series of evidences suggests that enhanced susceptibility to programmed cell death (PCD) is a major pathogenetic factor in Alzheimer's disease (AD). We investigated this issue, analyzing amyloid beta-protein (A beta) production in a model of neuronal PCD, induced by staurosporine in a murine neuroblastoma cell line. When PCD was induced, a 280-290% secreted A beta occurred, in spite of a 20% metabolism and an unchanged A betaPP expression.