Synergistic induction of nitric oxide by beta-amyloid and cytokines in astrocytes.
The deposition of beta-amyloid peptides in the brain in form of senile plaque is the key event responsible for Alzheimer pathology. Among various mechanisms that have been proposed to explain the neurotoxicity of beta-amyloid deposits, a new one, recently identified in our laboratory, suggests that beta-amyloid peptides may be indirectly toxic for neurons by activating microglial cells to produce NO (2). We have investigated if astrocytes, nerve cells that play an important role in many brain diseases, also might be involved in a similar mechanism of neuronal damage. The results have demonstrated that (1) beta-amyloid peptide (25-35), in the presence of IFN gamma or TNF alpha, induces the production of NO in the astrocyte cell line C6, while neither cytokine was effective per se; (2) NO generation is also synergically induced by beta-amyloid peptide (25-35) in the presence of IL-1 beta, the latter being a cytokine able to activate astrocytes per se; (3) the effect of beta-amyloid peptide (25-35) is due to the induction of the expression of the gene of inducible NO-synthase. These findings suggest that astrocytes, activated by deposited beta-amyloid peptides and cytokines, may play a role in neuronal damage via the indirect NO mechanism.
Rossi
F
F
Institute of General Pathology, University of Verona, Italy.
Bianchini
E
E
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002460:Cell Line; D007371:Interferon-gamma / Q000378:metabolism*; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000235:genetics; D010446:Peptide Fragments / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C074636:amyloid beta-protein (25-35); D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase