Differential effect of 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) on αB-crystallin and hsp70 gene expression in murine cell lines

We studied the effect of isoquinolinesulfonamide derivatives (H-7, H-8, and HA 1004) on the expression of two heat shock genes ( αB - crystallin and hsp70 ) in NIH 3T3 and Swiss 3T3 cells after heat shock at 45° for 10 min. Western blots and northern blots showed that H-7 effectively suppressed the accumulation of HSP70 and αB-crystallin mRNA as well as the synthesis of their proteins. The degree of suppression was dependent upon the concentration of the drug. Moreover, the expression of the hsp genes was differentially suppressed by H-7. The expression of the αB - crystallin gene was more effectively inhibited than that of the hsp70 gene by H-7. Nuclear run-on assay demonstrates that this difference was due to the differential effect of H-7 on the elongation of transcription of different hsp genes.