Effect of 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) on HSP70 and HSP28 gene expression and thermotolerance development in human colon carcinoma cells.
The effect of 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), a potent protein kinase C (PKC) inhibitor, on the development of thermotolerance and expression of heat shock genes (HSP70 and HSP28) was investigated in human colon carcinoma HT-29 cells. After acute heating at 45 degrees for 15 min, cells became resistant to a challenge heat shock. The development of thermotolerance was suppressed by adding H-7 after heat shock. Northern blots show that the levels of HSP70 and HSP28 mRNA increased rapidly and reached maximal values within 6 hr. H-7 suppressed the accumulation of HSP70 and HSP28 mRNA as well as their protein synthesis, and the level of suppression was concentration dependent. However, little effect was observed if the drug was added 1 hr before and during heat shock. These results suggest that PKC is involved in the regulation of heat shock gene expression after acute heat shock.
Lee
Y J
YJ
Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI 48073.
Berns
C M
CM
Erdos
G
G
Borrelli
M J
MJ
Ahn
C H
CH
Corry
P M
PM
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015870:Gene Expression / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006358:Hot Temperature; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000032:analysis; D013449:Sulfonamides; D014407:Tumor Cells, Cultured
D018840:HSP70 Heat-Shock Proteins; D007546:Isoquinolines; D010879:Piperazines; D012333:RNA, Messenger; D013449:Sulfonamides; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D011493:Protein Kinase C