title: TAT-BH4 counteracts Abeta toxicity on capillary endothelium.
abstract: Oxidative stress is one of the factor contributing to blood brain barrier degeneration. This phenomenon is observed during pathological conditions such as Alzheimer's disease or cerebral amyloid angiopathy in which brain haemorrhages are very frequent. Both diseases are characterized by beta amyloid peptide deposition either in neurons or in vessels. Oxidative stress leads to impairment of mitochondrial functions and apoptotic cell death subsequent to caspases activation. In this paper we demonstrate that BH4 domain of Bcl-xl administrated to endothelial cells as the conjugated form with TAT peptide, reverts Abeta-induced apoptotic cell death by activating a survival programme which is Akt/endothelial nitric oxide synthase dependent.
authors.affiliation: Department Molecular Biology, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy. cantara@unisi.it
authors.forename: S
authors.initials: S
authors.lastname: Cantara
authors.forename: P E
authors.initials: PE
authors.lastname: Thorpe
authors.forename: M
authors.initials: M
authors.lastname: Ziche
authors.forename: S
authors.initials: S
authors.lastname: Donnini
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D015696:Gene Products, tat / Q000494:pharmacology*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D017434:Protein Structure, Tertiary / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D015696:Gene Products, tat; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3