Modulation of the stress response during apoptosis and necrosis induction in cadmium-treated U-937 human promonocytic cells.

Abstract

Treatment for 2 h with 200 microM cadmium chloride, followed by recovery, caused apoptosis and induced heat-shock protein 70 (HSP70) expression in U-937 promonocytic cells. However, pre-incubation with the GSH depleting agent L-buthionine-[S,R]-sulfoximine (BSO, 1 mM for 24 h) caused necrosis instead of apoptosis and failed to induce HSP70 expression. This failure was a consequence of necrosis instead of GSH depletion, since BSO allowed or even potentiated HSP70 induction when used in combination with heat shock (2 h at 42.5 degrees C) or with 50 microM cadmium, which caused apoptosis. The administration of N-acetyl-L-cysteine (NAC) at the beginning of recovery after BSO/200 microM cadmium treatment prevented the execution of necrosis and restored the execution of apoptosis, but did not restore HSP70 induction, indicating that the inhibition by BSO of HSP70 expression is an early regulated event. This contrasted with the capacity of NAC to prevent the alterations caused by BSO/200 microM cadmium in other proteins, namely the suppression of Bax expression and the increase in Bcl-2 and HSP-60 expression. Finally, it was observed that treatment with 200 microM cadmium rapidly increased the HSP70 mRNA level and stimulated heat-shock factor 1 (HSF1) trimerization and binding, and that these effects were prevented by pre-incubation with BSO. Taken together, these results indicate that the stress response is compatible with apoptosis but not with necrosis in cadmium-treated promonocytic cells. The suppression of the stress response is specifically due to the early inhibition of HSF1 activation.

• Authors: A Galán, A Troyano, N E Vilaboa, C Fernández, E de Blas, P Aller
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1538 Issue 1 Pg. 38-46 (Feb 05 2001) ISSN: 0006-3002 [Print] Netherlands
• PMID: 11341981 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BAX protein, human
• Chaperonin 60
• DNA-Binding Proteins
• HSF1 protein, human
• HSP70 Heat-Shock Proteins
• Heat Shock Transcription Factors
• Proto-Oncogene Proteins
• Proto-Oncogene Proteins c-bcl-2
• RNA, Messenger
• Transcription Factors
• bcl-2-Associated X Protein
• buthionine sulfoximine ethyl ester
• Methionine Sulfoximine
• Glutathione
• Cadmium Chloride
• Acetylcysteine

Topics

• Acetylcysteine
• Apoptosis
• Cadmium Chloride (pharmacology)
• Chaperonin 60 (analysis)
• DNA-Binding Proteins (metabolism)
• Dose-Response Relationship, Drug
• Glutathione (deficiency)
• HSP70 Heat-Shock Proteins (biosynthesis, metabolism)
• Heat Shock Transcription Factors
• Hot Temperature
• Humans
• Methionine Sulfoximine (analogs & derivatives)
• Monocytes (drug effects)
• Necrosis
• Proto-Oncogene Proteins (analysis)
• Proto-Oncogene Proteins c-bcl-2 (analysis)
• RNA, Messenger (biosynthesis)
• Transcription Factors
• Tumor Cells, Cultured
• bcl-2-Associated X Protein