Serial analysis of gene expression in the rat striatum following methamphetamine

SAGE文库由用盐水或METH（40 mg/kg）处理并在2小时后处死的动物产生。两个库之间共有315个转录本差异表达（P < 0.05），其中179个（56%）因METH注射而上调，136个（44%）下调。其中，CAATT增强子结合蛋白同源蛋白（CHOP）/GADD 153（生长停滞和DNA损伤诱导基因153）被发现上调约3倍。对CHOP（DOC）下游基因表达的分析显示，其表达显著增加。由于DOC 1是碳酸酐酶（CA）的类似物，参与二氧化碳和碳酸氢根离子之间的相互转化，我们还测量了METH对几种CA表达的影响。METH以时间依赖性方式显著上调这些。这些结果表明，METH毒性是介导的，在一定程度上，由药物诱导的生理过程，依赖于正常的pH值和CO（2）稳态的扰动。

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.