Beatrice Sampaolese

Aβ(31–35) peptide induce apoptosis in PC 12 cells: Contrast with Aβ(25–35) peptide and examination of underlying mechanisms

Abstract The toxic behaviour of the two shorter sequences of the native Aβ amyloid peptide required for cytotoxicity i.e., Aβ(31–35) and Aβ(25–35) peptides, was studied. We have shown that Aβ(31–35) peptide induces neurotoxicity in undifferentiated PC 12 cell via an apoptotic cell death pathway, including caspase activation and DNA fragmentation. Aβ(25–35) peptide, like the shorter amyloid peptide has the ability to induce neurotoxicity, as evaluated by the MTS reduction assay and by adherent cell count, but the Aβ(25–35) peptide-induced neurotoxicity is not associated with any biochemical features of apoptosis. The differences observed between the neurotoxic properties of Aβ(31–35) and Aβ(25–35) peptides might result on their different ability to be internalised within the neuronal cells. Furthermore, this study reveals that the redox state of methionine residue, C-terminal in Aβ(31–35) and Aβ(25–35) peptides affect in a different way the toxic behaviour of these two short amyloid fragments. Taken together our results suggest that Aβ(31–35) peptide induces cell death by apoptosis, unlike the Aβ(25–35) peptide and that role played by methionine-35 in Aβ induced neurotoxicity might be related to the Aβ aggregation state.

β-amyloid decreases detectable endothelial nitric oxide synthase in human erythrocytes: a role for membrane acetylcholinesterase

Until few years ago, many studies of Alzheimers disease investigated the effects of this syndrome in the central nervous system. Only recently, the detection of amyloid beta peptide (Aβ) in the blood has evidenced the necessity to extend studies on extraneuronal cells, particularly on erythrocytes. Aβ is also present in brain capillaries, where it interacts with the erythrocytes, inducing several metabolic and functional alterations. Recently, functionally active endothelial type nitric oxide synthase (eNOS) was discovered in human erythrocytes. The goal of the present study was to evidence the effect of Aβ on erythrocyte eNOS. We found that Aβ following to 24‐h exposure causes a decrease in the immune staining of erythrocyte eNOS. Concurrently, Aβ alters erythrocyte cell morphology, decreases nitrites and nitrates levels, and affects membrane acetylcholinesterase activity. Propidium, an acetylcholinesterase inhibitor, was able to reverse the effects elicited by Aβ. These events could contribute to the vascular alterations associated with Alzheimers disease disease. Copyright

S100b induces expression of Myoglobin in APβ treated neuronal cells in vitro: a possible neuroprotective mechanism.

BACKGROUND In this study, human neuroblastoma cells (IMR32) treated with Amyloid Beta Peptide (APβ), were used as model to evaluate the molecular basis of protective role of S100b, a neurotrophic factor and neuronal survival protein, highly expressed by reactive astrocytes close to amyloid deposition in the cortex of Alzheimers patients. The aim of this work is to value the effect of S100b on ROS production in cells treated with Amyloid Beta Peptide and the subsequent influence on globin gene expression. METHOD In this study we investigated the effect of S100b on ROS production and on globin gene expression in human neuroblastoma cells (IMR32) treated with Amyloid Beta Peptide (APβ). RESULTS Our results have shown that at nanomolar concentrations, S100b protects cells against AP. mediated cytotoxicity and the protective mechanism could be related, almost in part, to the control of ROS production through an over expression of Myoglobin gene. CONCLUSION In light of our results, we speculate that over-expression of the Myoglobin gene could be read as a possible attempt of the cell to increase the scavengers of reactive oxygen species (ROS).

Fibroblast apoptosis in a patient affected by lamellar ichthyosis

Background:  Lamellar ichthyosis (LI) is a congenital recessive skin disorder characterized by generalized scaling and hyperkeratosis. The pathology may be caused by mutations in transglutaminase 1 (TGM1) gene that encodes an enzyme critical for terminally differentiating keratinocytes. Because of evidences that transglutaminase enzymes are involved in programmed cell death, we investigated morphological and biochemical apoptotic parameters in cultured skin fibroblasts from a patient with a severe LI and homozygous for the TGM1 R142H mutation.

Changes In Erythrocyte Deformability In Alzheimer's Disease: A Role For Nitric Oxide Synthase

Background: Until few years ago, most studies of Alzheimers disease (AD) investigated the effects of this syndrome in the CNS. Only recently, several evidences suggest that many abnormalities in vascular could be responsible for the AD. In particular, the reduced deformability of erythrocytes is one of the most suspected events associated to vascular abnormalities in AD. At this regard NO was proposed to be a regulatory factor of RBC mechanical properties since inhibitors of endogenous NO synthesis induce decreased erythrocyte deformability.