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Inflammatory neurodegeneration induced by lipoteichoic acid from Staphylococcus aureus is mediated by glia activation, nitrosative and oxidative stress, and caspase activation
Author(s) -
Kinsner Agnieszka,
Pilotto Valentina,
Deininger Susanne,
Brown Guy C.,
Coecke Sandra,
Hartung Thomas,
BalPrice Anna
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03422.x
Subject(s) - lipoteichoic acid , neurodegeneration , oxidative stress , staphylococcus aureus , chemistry , microbiology and biotechnology , biochemistry , biology , bacteria , medicine , pathology , genetics , disease
In this study we investigated the mechanisms of neuronal cell death induced by lipoteichoic acid (LTA) and muramyl dipeptide (MDP) from Gram‐positive bacterial cell walls using primary cultures of rat cerebellum granule cells (CGCs) and rat cortical glial cells (astrocytes and microglia). LTA (± MDP) from Staphylococcus aureus induced a strong inflammatory response of both types of glial cells (release of interleukin‐1β, tumour necrosis factor‐α and nitric oxide). The death of CGCs was caused by activated glia because in the absence of glia (treatment with 7.5 µ m cytosine‐ d ‐arabinoside to inhibit non‐neuronal cell proliferation) LTA + MDP did not cause significant cell death (less than 20%). In addition, staining with rhodamine‐labelled LTA confirmed that LTA was bound only to microglia and astrocytes (not neurones). Neuronal cell death induced by LTA (± MDP)‐activated glia was partially blocked by an inducible nitric oxide synthase inhibitor (1400 W; 100 µ m ), and completely blocked by a superoxide dismutase mimetic [manganese (III) tetrakis (4‐benzoic acid)porphyrin chloride; 50 µ m ] and a peroxynitrite scavenger [5,10,15,20‐tetrakis (4‐sulfonatophenyl) porphyrinato iron (III); 100 µ m ] suggesting that nitric oxide and peroxynitrite contributed to LTA‐induced cell death. Moreover, neuronal cell death was inhibited by selective inhibitors of caspase‐3 (z‐DEVD‐fmk; 50 µ m ) and caspase‐8 (z‐Ile‐Glu(O‐Me)‐Thr‐Asp(O‐Me) fluoromethyl ketone; 50 µ m ) indicating that they were involved in LTA‐induced neuronal cell death.