SAGE libraries were generated from animals treated with either saline or METH (40 mg/kg) and sacrificed 2 h later. A total of 315 transcripts were differentially expressed between the two libraries (P < 0.05), with 179 (56%) being upregulated and 136 (44%) being downregulated by the METH injection. Of these, CAATT enhancer-binding protein homologous protein (CHOP)/GADD153 (growth arrest- and DNA damage-inducible gene 153) was found to be upregulated by about threefold. Analysis of the expression of genes downstream of CHOP (DOCs) revealed significant METH-induced increases in their expression. Because DOC1 is an analog of carbonic anhydrase (CA) which is involved in the interconversion between carbon dioxide and the bicarbonate ion, we also measured the effects of METH on the expression of several CAs. These were significantly upregulated by METH in a time-dependent fashion. These results indicate that METH toxicity is mediated, in part, by drug-induced perturbations of physiological processes that are dependent on normal pH and CO(2) homeostasis.
| Cai, Ning Sheng; Cadet, Jean Lud (2008) The combination of methamphetamine and of the HIV protein, Tat, induces death of the human neuroblastoma cell line, SH-SY5Y. Synapse 62:551-2 |
| Cai, Ning Sheng; McCoy, Michael T; Ladenheim, Bruce et al. (2006) Serial analysis of gene expression in the rat striatum following methamphetamine administration. Ann N Y Acad Sci 1074:13-30 |
