Lipopolysaccharide Protects Primary B Lymphocytes from Apoptosis by Preventing Mitochondrial Dysfunction and Bax Translocation to Mitochondria

ABSTRACT Mature B lymphocytes undergo apoptosis when they are cultured in the absence of survival factors. Gram-negative bacterial lipopolysaccharide (LPS) prevents this spontaneous apoptosis. This study aimed to better define the signaling pathway(s) involved in the antiapoptotic activity of this endotoxin. We report here that, in addition to its effects on spontaneous apoptosis, LPS protects B cells from apoptosis induced by the broad-spectrum protein kinase inhibitor staurosporine. LPS increased cell viability and concomitantly maintained the mitochondrial transmembrane potential (ΔΨm) and high glutathione levels. Moreover, LPS inhibited cytosolic cytochrome c release and decreased caspase-9 activation. Unlike staurosporine, LPS induced the retention of Bax, a proapoptotic protein of the Bcl-2 family, in the cytosol by preventing its translocation to mitochondria. These results suggest that Bax relocalization from the cytosol to the mitochondria is an important step of mature B-cell apoptosis and that the antiapoptotic activity of LPS occurs upstream of mitochondrial events.

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