Phospholipse c inhibitor, u73122, stimulates release of hsp-70 stress protein from A431 human carcinoma cells.
BACKGROUND: Accumulating evidences suggest that Hsp 70, the inducible component of Hsp70 family, might release from a living cell. Here we show that a pharmacological inhibitor of phospholipase C activity U73122 caused a 2-4 fold reduction of an intracellular level of Hsp70 in A431 human carcinoma cells. RESULTS: A depletion of Hsp70 under U73122 was a result of the protein release since it was detected in cell culture medium, as was established by immunoprecipitation and precipitation with ATP-agarose. The reduction of Hsp70 level was specifically attributed to the inhibition of PLC, since the non-active inhibitor, U73343, had no effect on Hsp70 level. The PLC-dependent decrease of Hsp70 intracellular level was accompanied by the enhanced sensitivity of A431 cells to the apoptogenic effect of hydrogen peroxide. Here for the first time we demonstrated one of the possibilities for a cell to export Hsp70 in PLC-dependent manner. CONCLUSION: From our data we suggest that phospholipase C inhibition is one of the possible mechanisms of Hsp70 release from cells.
Institute of Cytology, St-Petersburg, Russia. evdonin@mail.ru
Anton L
AL
Evdonin
Irina V
IV
Guzhova
Boris A
BA
Margulis
Natalia D
ND
Medvedeva