Apoptosis of human primary B lymphocytes is inhibited by N-acetyl-L-cysteine.
Thiols are important molecules to control apoptosis. This study examined the effect of N-acetyl-L-cysteine (NAC) on in vitro spontaneous apoptosis of human tonsillar B lymphocytes (TBL). Results show that NAC inhibits TBL apoptosis and maintains their survival in vitro. The antiapoptotic action of NAC is progressively reduced when its addition to culture is delayed, is reversible, and is not blocked by cycloheximide. The antiapoptotic activity of NAC is associated with its ability to inhibit caspase-3 and -7 proteolytic processing, DNA-fragmentation factor 45 cleavage, and DNA fragmentation. Furthermore, NAC inhibits BID cleavage and cytochrome c release from mitochondria and increases the expression of Bcl-2 and Bcl(XL) survival proteins. However, it has no effect on caspase-9 cleavage and increases that of caspase-8 and poly(adenosine 5'-diphosphate-ribose)polymerase. We conclude that NAC-induced inhibition of TBL apoptosis is associated with inhibition of caspase-3 and -7 processing and is accompanied by changes in several regulatory components of the apoptotic process. These results pose the question of whether microenvironment thiols may in part contribute to in vivo B cell survival.
Rosati
Emanuela
E
General Pathology and Immunology Section, University of Perugia, Via Brunamonti, General Hospital-Monteluce 06100 Perugia, Italy.
Sabatini
Rita
R
Ayroldi
Emira
E
Tabilio
Antonio
A
Bartoli
Andrea
A
Bruscoli
Stefano
S
Simoncelli
Costantino
C
Rossi
Ruggero
R
Marconi
Pierfrancesco
P
D000111:Acetylcysteine / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D015153:Blotting, Western; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D045304:Cytochromes c / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology; D013997:Time Factors
D000998:Antiviral Agents; D045304:Cytochromes c; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases; D000111:Acetylcysteine