S100B Expression Plays a Crucial Role in Cytotoxicity, Reactive Oxygen Species Generation and Nitric Oxide Synthase Activation Induced by Amyloid β-Protein in an Astrocytoma Cell Line

Abstract

S100B is an astrocytic cytokine that has been shown to be involved in several neurodegenerative diseases. We used an astrocytoma cell line (U373 MG) silenced for S100B, and stimulated it with amyloid beta-peptide (Aβ) as a known paradigm factor for astrocyte activation, and showed that the ability of the cell (including the gene machinery) to express S100B is a prerequisite for inducing reactive astrocytic features, such as ROS generation, NOS activation and cytotoxicity. Our results showed that control astrocytoma cell line exhibited overexpression of S100B after Aβ treatment, and subsequently cytotoxicity, increased ROS generation and NOS activation. In contrast, cells silenced with S100B were essentially protected, consistently reducing cell death, significantly decreasing oxygen radical generation and nitric oxide synthase activity. The conclusive aim of the present study was to show a causative linkage between the cell expression of S100B and induction of astrocyte activation processes, such as cytotoxicity, ROS and NOS activation.

Biochemical and Anthropometric Parameters for the Early Recognition of the Intrauterine Growth Restriction and Preterm Neonates at Risk of Impaired Neurodevelopment

“…Thus, the BBB in IUGR and preterm neonates with negative outcomes may be characterized with a disrupted integrity or altered permeability. Further studies in all these directions are needed, including additional investigations concerning the possible extracerebral release of S100B, and methodological problems surrounding its measurements [10,15,58].…”

“…It regulates several cellular functions (i.e., cell growth, cell structure, and energy metabolism), stimulates neurite growth, and promotes neuronal survival [9]. At higher levels (micromolar level), S100B displays neurotoxic effects, including the impairments in synaptic plasticity and spatial learning, and the apoptosis of astrocytes and their neighboring neurons [7,8] induced by the stimulation of ROS and NOS production [10]. Its presence in the extracellular space may be due to its leakage from damaged cells [11], or to active secretion, thus functioning as an extracellular signaling molecule with concentrationdependent effects [11,12].…”