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Transcriptional activation of nitric oxide synthase‐2, and NO‐induced cell death, in mouse cerebrovascular endothelium exposed to Neisseria meningitidis
Author(s) -
Constantin Despina,
Ala'Aldeen Dlawer,
Murphy Sean
Publication year - 2002
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 - 10.1046/j.1471-4159.2002.00816.x
Subject(s) - neisseria meningitidis , nitric oxide synthase , nitric oxide , endothelium , endothelial nitric oxide synthase , programmed cell death , microbiology and biotechnology , biology , chemistry , biochemistry , endocrinology , bacteria , genetics , apoptosis , enos
The site and mechanisms by which meningococci gain access to the CNS are unclear. In this study we determined whether production of nitric oxide (NO) is part of the host (endothelial cell) response to meningococcal cell lysate, and the consequences for endothelial cell viability. Expression of NO synthase type II (NOS‐2) mRNA, protein and enzyme activity were investigated in mouse cerebrovascular endothelial cells exposed to sonicated Neisseria meningitidis . The production of nitrite peaked after 48 h of incubation, and this reflected transcriptional activation of the NOS‐2 gene and increased expression of the NOS‐2 protein. This endothelial response was independent of meningococcal lipopolysaccharide production. Endothelial cell death occurred as a result of NO production, and addition of a NOS inhibitor prevented cell death, but the cells did not exhibit features of apoptosis. However, inhibition of poly (ADP‐ribose) polymerase (PARP) decreased the rate of cell death by more than 40%. These data indicate that N. meningitidis increases expression of NOS‐2 in endothelial cells and causes cell death. Such an effect could contribute to meningococcal entry into the CNS in situ .