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Bcl-2 down modulation in WEHI-3B/CTRES cells resistant to Cholera Toxin(CT)-induced apoptosis

Cell Research 2006年第3期16卷 306-312页

作者： Augusto Pessina Cristina Croera Nicoletta Savalli arianna bonomi Loredana Cavicchini Elisa Turlizzi Fabiana Guizzardi Lucia Guido Laura Daprai Maria GraziaNeri Institute of Microbiology University of MilanVia Pascal 3620133 MilanItaly ECVAM Institute for Health and Consumer ProtectionEuropean Commission Joint Research CentreIspra 21020Italy UCLA Department of AnesthesiologyLos AngelesCA 90095USA

The very different effects of Cholera Toxin (CT) on cell growth and proliferation may depend on the type of ganglio-side receptors in cell membranes and different signal transduction mechanisms triggered,but other functions relatedto the drug resistance mechanisms can not be *** effect of CT treatment on the "in vitro" clonogenicity,thePopulation Doubling Time (PDT),apoptosis,PKA activation and Bax and Bcl-2 expression was evaluated in WEHI-3Bcell line and its CT-resistant subclone (WEHI-3B/CTRES).In WEHI-3B parental cells the dramatic accumulation ofcAMP induced by CT correlated well with PKA activation,increased PDT value,inhibition of clonogenicity and apop-tosis.H-89 treatment inhibited PKA activation by CT but did not protect the cells from apoptosis and growth *** WEHI-3B/CTRES no significant CT-dependent accumulation of cAMP occurred with any increase of PKA activityand *** CT resistant cells (WEHI-3B/CTRES),Bcl-2 expression was down regulated by both CT or drug treatment(eg.,ciprofloxacin,CPX) although these cells were protected from CT-dependent apoptosis but not from *** from other cell models described,down regulation of Bcl-2 is proved to be independent on cAMPaccumulation and PKA *** observations support the implication of cAMP dependent kinase (PKA) in theinhibition of WEHI-3B cells growth and suggest that,in WEHI-3B/CTRES,Bcl-2 expression could be modulated byCT in the absence of cAMP *** in consideration of many contradictory data reported in literature,ourcell models(of one sensitive parental cell strain and two clones with different uncrossed specific resistance to CT andCPX)provides a new and interesting tool for better investigating the relationship between the CT signal transductionmechanisms and Bcl-2 expression and function.

关键词： cholera toxin Bcl-2 PKA apoptosis ciprofloxacin resistance

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