METABOLIC OXIDATIVE STRESS-INDUCED HSP70 GENE-EXPRESSION IS MEDIATED THROUGH SAPK PATHWAY - ROLE OF BCL-2 AND C-JUN NH2-TERMINAL KINASE

In previous reports we demonstrated that glucose deprivation induces m etabolic oxidative stress in drug-resistant human breast carcinoma MCF -7/ADR cells (Lee, Y. J., Galoforo, S. S., Berns, c. M., Chen, J. C., Davis, B. H., Swim, J. E., Corry, P. M., and Spitz, D. R. (1998) J. Bi ol. Chem. 273, 5294-5299). In the study described here, we investigate d intracellular responses to metabolic oxidative stress. Northern blot s show an increase in the level of HSP70 and HSP28 mRNA in cells expos ed to glucose-free medium for 1 h, One and two-dimensional polyacrylam ide gel analyses confirmed that glucose deprivation induced a family o f HSPs, particularly an inducible HSP70. Overexpression of bcl-2 suppr essed glucose deprivation-induced HSP70 gene expression, heat shock tr anscription factor-heat shock element binding activity, as well as c-J un NH2-terminal kinase (JNK1) activation. Expression of a dominant-neg ative mutant of JNK1 also suppressed glucose deprivation-induced JNK1 activation as well as HSP70 gene expression. Taken together, the stres s-activated protein kinase signal transduction pathway is involved in glucose deprivation-induced heat shock gene expression.