The effects of some Mannich bases on heat shock proteins HSC70 and GRP75, and thioredoxin and glutaredoxin levels in Jurkat cells.
Mannich bases interact with cellular thiols and inactivate thioredoxin reductase. In this study, the effects of cytotoxic mono-Mannich bases 2, 3 and cyclic Mannich base C1 on the expression of cytoprotective heat shock proteins (HSC70 and GRP75) and on levels of thioredoxin (TRX) and glutaredoxin (GRX) were investigated in Jurkat cells. Cells were exposed to the compounds for 24 h in cell culture medium with 1% FBS. C1 and 2 increased the levels of HSC70 (200% of control) in all the concentrations tested, but 3 did not affect HSC70 levels. Whereas 3 increased GRP75 expression (123-154%), 2 and C1 either did not affect (95-87% for 2, and 88% for C1) or slightly decreased GRP75 expression (82% for 2 and 67% for C1). Mannich bases generally decreased GRX levels (68%, 63-77% and 33-71% for 2, 3 and C1, respectively), but 3 increased GRX levels at 1 microg/ml (142%). Whereas 2 and 3 decreased TRX levels (30-79% and 37-44% of control, respectively), C1 increased the expression of TRX (156-201%). Our results suggest that decreases in GRX and TRX due to the alkylating effects of Mannich bases might have prevented cell division and decreased survival in Jurkat cells, which could not be prevented by increased heat shock protein expression.
Gul
Mustafa
M
Department of Physiology, Faculty of Medicine, University of Kuopio, 70211 Kuopio, Finland.
Atalay
Mustafa
M
Gul
Halise Inci
HI
Nakao
Chitose
C
Lappalainen
Jani
J
Hänninen
Osmo
O
D054477:Glutaredoxins; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis*; D006801:Humans; D019169:Jurkat Cells; D008352:Mannich Bases / Q000494:pharmacology*; D008565:Membrane Proteins / Q000032:analysis*; D010088:Oxidoreductases / Q000032:analysis*; D013879:Thioredoxins / Q000032:analysis*
C516005:GLRX protein, human; D054477:Glutaredoxins; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D008352:Mannich Bases; D008565:Membrane Proteins; C018551:glucose-regulated proteins; D013879:Thioredoxins; D010088:Oxidoreductases