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Oxidative Upregulation of Bcl‐2 in Healthy Lymphocytes
Author(s) -
CRISTOFA SILVIA,
NUCCITELLI SILVIA,
D'ALESSIO MARIA,
RADOGNA FLAVIA,
DE NICOLA MILENA,
BERGAMASCHI ANTONIO,
CERELLA CLAUDIA,
MAGRINI ANDREA,
DIEDERICH MARC,
GHIBELLI LINA
Publication year - 2006
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1378.049
Subject(s) - downregulation and upregulation , oxidative phosphorylation , chemistry , medicine , biochemistry , gene
Abstract: In many cell systems, pharmacological glutathione (GSH) depletion with the GSH neosynthesis inhibitor buthionine sulfoximine (BSO) leads to cell death and highly sensitizes tumor cells to apoptosis induced by standard chemotherapeutic agents. However, some tumor cells upregulate Bcl‐2 in response to BSO, thus surviving the treatment and failing to be chemosensitized. Cell lines of monocytic and lymphocytic origins respond to BSO treatment in an opposite way, lymphocytes being chemosensitized and unable to transactivate Bcl‐2. In this article we investigate the response to BSO of lymphocytes freshly isolated from peripheral blood of healthy donors. After ensuring that standard separation procedures do not alter per se lymphocytes redox equilibrium nor Bcl‐2 levels in the first 24 h of culture, we show that BSO treatment promotes the upregulation of Bcl‐2, with a mechanism involving the increased radical production consequent to GSH depletion. Thus, BSO treatment may increase the differential cytocidal effect of cytotoxic drugs in tumor versus normal lymphocytes.

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