Effect of isoquinolinesulfonamides on heat shock gene expression during heating at 41 degrees C in human carcinoma cell lines.
The possible involvement of PKC in the regulation of heat shock genes expression was investigated with three isoquinolinesulfonamide derivatives (H-7, H-8, and HA1004) in DUT-145, MCF-7, and MCF-7/ADR cells. The drug was added 1 hr before and during heating at 41 degrees C. Northern blots show that the levels of HSP70 and HSP28 mRNA increased rapidly and reached maximal values within 4-8 hr and 8-12 hr, respectively. H-7 and H-8 which are potent PKC inhibitors selectively suppressed the accumulation of HSP70 mRNA as well as the synthesis of HSP70. In contrast, HA1004 which is a potent PKA inhibitor but a weak PKC inhibitor did not affect HSP70 gene expression. These results suggest that PKC rather than PKA plays an important role in the regulation of heat shock gene expression.
Lee
Y J
YJ
Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan 48073.
Berns
C M
CM
Erdos
G
G
Corry
P M
PM
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015152:Blotting, Northern; D001943:Breast Neoplasms; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000302:isolation & purification; D006358:Hot Temperature; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D007700:Kinetics; D007930:Leucine / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D011471:Prostatic Neoplasms; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D013449:Sulfonamides; D014407:Tumor Cells, Cultured
D006360:Heat-Shock Proteins; D007546:Isoquinolines; D010879:Piperazines; D012333:RNA, Messenger; D013449:Sulfonamides; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C053177:N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D007930:Leucine