Publications by authors named "Evelyn Tiffany-Castiglioni"

Secretion of granular glands from the skin of amphibians is a fascinating resource of active substances, particularly for cancer therapy in clinical practice of Traditional Chinese Medicine. A variety of anti-tumor peptides have been isolated from different toads and frogs; however, no anti-tumor peptides are reported in toad venom of . Firstly, soluble fraction from fresh toad venom (FTV) was compared with that from dried toad venom (DTV), using HPLC analysis.

View Article and Find Full Text PDF

Chaperones are essential for the proper folding of proteins, and their dysfunction or depletion may be a key factor in protein folding disorders in the central nervous system. In normal conditions the cell regulates the proper folding of proteins by endoplasmic reticulum chaperones, called heat shock proteins, the cellular machinery that correctly folds newly synthesized and partially folded proteins or initiates degradation of misfolded proteins. Maintaining protein homeostasis within the cell is vital for the cells to function and survive.

View Article and Find Full Text PDF

Our previous study indicated that Hspa5 directly interacts with copper (Cu) to maintain Cu homeostasis in astrocytes. In this study, we explored the possibility that Cu forms a specific complex with Hspa5 by assaying stoichiometric binding of Cu and other metals to recombinant human HSPA5 (rh-HSPA5) in silico. Spectrophotometric analysis showed that incubation of rh-HSPA5 with Cu but not with Fe, Mn, Zn, or Pb in the presence of ascorbic acid produced an absorbance peak at 470 nm.

View Article and Find Full Text PDF

Chaperones in the endoplasmic reticulum play vital roles in the folding, assembly, and post-translational modification of secretory proteins and also recycle, refold, or initiate degradation of misfolded proteins. Chaperone deficiencies in either amount or function are implicated in the etiology or pathogenesis of Alzheimer's disease and other protein folding disorders of the central nervous system. In this review, we discuss evidence that chaperones become pathologic through deleterious interactions with metals and then promote protein folding disorders.

View Article and Find Full Text PDF

Copper (Cu) ion availability in tissues and cells must be closely regulated within safe limits by Cu transporters and chaperones. Astrocytes play key roles in metal homeostasis and distribution in the brain that are only partially understood. The purpose of this study was to define the role that the protein chaperone Hspa5, also known as Grp78, plays in Cu homeostasis in astrocytes.

View Article and Find Full Text PDF

Copper (Cu) is an essential trace element in the brain that can be toxic at elevated levels. Cu accumulation is a suspected etiology in several neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and prion-induced disorders. Astrocytes are a proposed depot in the brain for Cu and other metals, including lead (Pb).

View Article and Find Full Text PDF

Molecular chaperones assist the folding of nascent proteins during translation into their correct conformations. Neurotoxic metals such as copper (Cu) and lead (Pb) may produce a deficiency in chaperone function that compromises protein secretion and exacerbates protein aggregation, potentially promoting neurodegenerative diseases that exhibit protein aggregation. Because astrocytes function as depots in the brain for certain metals, including Cu and Pb, the interaction of metals with chaperones in these cells is of interest.

View Article and Find Full Text PDF

An adverse outcome pathway (AOP) is a sequence of key events from a molecular-level initiating event and an ensuing cascade of steps to an adverse outcome with population-level significance. To implement a predictive strategy for ecotoxicology, the multiscale nature of an AOP requires computational models to link salient processes (e.g.

View Article and Find Full Text PDF

Paraquat produces dopaminergic pathologies of Parkinson's disease, in which cyclooxygenase-2 (COX-2) is implicated. However, it is unclear whether paraquat induces toxicity within dopaminergic neurons through COX-2. To address this, human neuroblastoma SH-SY5Y cells were treated with paraquat and then the involving mechanism of COX-2 was investigated.

View Article and Find Full Text PDF

Valproate (VPA) is a commonly prescribed mood stabilizer. However, emerging evidence indicates that VPA administration may cause reversible symptoms of Parkinsonism and cognitive decline (P/CD) in some manic patients. The mechanism of this phenomenon is unknown.

View Article and Find Full Text PDF

Epidemiologic and laboratory studies suggest that paraquat can be an environmental etiologic factor in Parkinson's disease (PD). One mechanism by which paraquat may mediate cell death of dopaminergic neurons is by inducing endoplasmic reticulum (ER) stress, as suggested in a recent report. In this study, we further investigated this linkage by examining ER stress cascades.

View Article and Find Full Text PDF

Free intracellular calcium ([Ca(2+)](i)) controls a wide range of cellular functions such as contraction, neurotransmitter and hormone release, metabolism, cell division and differentiation. Cytosolic Ca(2+) levels are abnormal in cells exposed to toxicants and understanding how these levels become altered may improve our ability to design high-throughput methods for the sensitive detection of cellular responses to a toxic exposure. Because Ca(2+) is involved in multiple aspects of cellular function, its role in signaling is complex.

View Article and Find Full Text PDF

Quantification of polycyclic aromatic hydrocarbons (PAH) and their metabolites within living cells and tissues in real time using fluorescence methods is complicated due to overlaping excitation and/or emission spectra of metabolites. In this study, simultaneous analysis of several metabolites of a prototype carcinogenic PAH, benzo[a]pyrene (BaP) in undifferentiated (MCF10A) and differentiated (MCF10CA1h) breast cancer cells was performed using single-cell multiphoton spectral analysis. The two cell types were selected for this study because they are known to have differences in BaP uptake and metabolism and induction of aryl hydrocarbon receptor-dependent ethoxyresorufin-O-deethylase (EROD) activity.

View Article and Find Full Text PDF

The herbicide paraquat is a suspected etiologic factor in the development of Parkinson's disease (PD). Paraquat was therefore used to reproduce Parkinsonian syndromes in lab animals, in which it produces dopaminergic pathogenesis. However, the factors or mechanisms by which paraquat kills dopaminergic neurons are not fully understood.

View Article and Find Full Text PDF

Paraquat (PQ) is suspected to be an environmental risk factor for Parkinson's disease (PD). A strong correlation between exposure to paraquat and the occurrence of PD was reported in Canada, Taiwan, and the United States. This correlation is supported by in vivo work showing that paraquat produces dopaminergic pathogenesis.

View Article and Find Full Text PDF

Environmental injury has been associated with endoplasmic reticulum (ER) stress, a response characterized by activation of the unfolded protein response, proteasomal degradation of proteins, and induction of HSPA5, also known as GRP78 or BiP. Although HSPA5 has been implicated in the stress response to environmental injury in several cell types, its role in the glomerular ER stress response is unknown. In this study, we evaluated HSPA5 activation profiles in rat glomerular mesangial cells (rGMCs) challenged with heavy metals (HgCl2 or Pb2+ acetate) or polycyclic aromatic hydrocarbons (PAHs, ie, benzo(a)pyrene [BaP]).

View Article and Find Full Text PDF

Interleukin (IL)-6 is a cytokine produced mainly by microglia and astrocytes and plays a pleiotropic role in the central nervous system. In this study, we cloned rat IL-6 cDNA into an enhanced green fluorescent protein (EGFP) or a red fluorescent protein (DsRed2) vector and rat 78-kDa glucose-regulated protein (GRP78) cDNA into an EGFP vector to construct IL-6-EGFP, IL-6-DsRed2, and GRP78-EGFP chimeras for the investigation of the mechanism of IL-6 secretion from astrocytes. The data showed that constructed IL-6-EGFP and IL-6-DsRed2 chimeras retained the secretory property, and the secretion of IL-6-EGFP from astrocytes could be attenuated by GRP78 depletion with double-stranded RNA interference.

View Article and Find Full Text PDF

The effects of propofol, a short-acting general anesthetic, upon cell growth and Ca(2+) signaling in a human astrocytic cell line were examined. Exposure of cells to graded concentrations of propofol resulted in a dose-dependent decrease in cell number with an inhibitory concentration of cell viability (IC50) of 31.7+/-1.

View Article and Find Full Text PDF

The objective of this study was to evaluate the comparative non-cholinergic neurotoxic effects of paraoxon, which is acutely neurotoxic, and diisopropyl fluorophosphate (DFP), which induces OPIDN, in the human neuroblastoma SY5Y and the human astrocytoma cell line CCF-STTG1. SY5Y cells have been studied extensively as a model for OP-induced neurotoxicity, but CCF cells have not previously been studied. We conducted a preliminary human gene array assay of OP-treated SY5Y cells in order to assess at the gene level whether these cells can distinguish between OP compounds that do and do not cause OPIDN.

View Article and Find Full Text PDF

In vitro systems have been proposed, but not yet demonstrated, as a method to assess the neurotoxicity of compounds in an efficient and rapid manner. Although such tests are desired both for pharmaceuticals and environmental agents, such a battery has yet to be developed that is based on known processes of nervous system dysfunction. In this review article, characteristics and potential limitations associated with in vitro methods are discussed.

View Article and Find Full Text PDF

Rapid and inexpensive methods are needed to investigate the interactions of complex mixtures. This commentary addresses the use of cell cultures to detect neurotoxicity of simple binary mixtures, which is a first step in the development of such methods. A small number of recent studies from our laboratory are examined.

View Article and Find Full Text PDF

Numerous approaches have been studied to degrade organophosphorus (OP) compounds and ameliorate their toxicity. In the current study, the potential of genetically engineered organophosphorus hydrolase (OPH) enzymes to functionally biotransform OP neurotoxicants was examined by assessing effects of OPH-hydrolyzed OPs on acute and delayed indicators of neurotoxicity. SY5Y human neuroblastoma cells were used as a model test system, as these cells respond distinctly to mipafox, which produces OP-induced delayed neuropathy, and paraoxon, which does not.

View Article and Find Full Text PDF

Paraquat (PQ) is a cationic nonselective bipyridyl herbicide widely used to control weeds and grasses in agriculture. Epidemiologic studies indicate that exposure to pesticides can be a risk factor in the incidence of Parkinson's disease (PD). A strong correlation has been reported between exposure to paraquat and PD incidence in Canada, Taiwan, and the United States.

View Article and Find Full Text PDF

Lead (Pb), depositing primarily in astroglia in the brain, is a well-known neurotoxicant and a risk factor for neurologic disorders. Pb has been reported to induce oxidative stress by probably the disturbance of copper (Cu) homeostasis in astroglia. Thus, we hypothesized that Pb-induced oxidative stress is initiated by interfering with Cu transporter in astroglia.

View Article and Find Full Text PDF

A PHP Error was encountered

Severity: Notice

Message: fwrite(): Write of 34 bytes failed with errno=28 No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 272

Backtrace:

A PHP Error was encountered

Severity: Warning

Message: session_write_close(): Failed to write session data using user defined save handler. (session.save_path: /var/lib/php/sessions)

Filename: Unknown

Line Number: 0

Backtrace: