Butyrate induced apoptosis in lymphoid cells preceded by transient over-expression of HSP70 mRNA.
In addition to inducing differentiation in several cell types sodium butyrate is cytotoxic to lymphoid cells and causes apoptosis in HL-60 cells. We report here that butyrate treatment of the Burkitt's lymphoma cell line BL-30 causes cell death by apoptosis, as established by nuclear changes and DNA fragmentation. The kinetics of induction of apoptosis by butyrate revealed a considerably delayed response in comparison to that observed with heat treatment. At 4 h after heat (43.5 degrees C) exposure, 50% of the cells were undergoing apoptosis whereas that level of apoptosis was only reached after 16 h of treatment with butyrate (5 mM). Apoptosis induced by both treatments was accompanied by a marked increase in hsp70 mRNA. The maximum response in mRNA preceded a rapid onset of apoptosis in both cases, and the response was transient. There was a corresponding increase in the level of hsp70 protein after exposure to both heat and butyrate which coincided with the pattern of increase in mRNA but protein levels remained high during the onset of apoptosis. The results obtained here provide further evidence for a relationship between differentiation and apoptosis.
Filippovich
I
I
Queensland Cancer Fund Research Unit, Queensland Institute of Medical Research, Bancroft Centre, Herston, Brisbane, Australia.
Sorokina
N
N
Khanna
K K
KK
Lavin
M F
MF
D017209:Apoptosis / Q000187:drug effects*; D015152:Blotting, Northern; D015153:Blotting, Western; D002051:Burkitt Lymphoma; D002087:Butyrates / Q000494:pharmacology* / Q000633:toxicity; D020148:Butyric Acid; D002460:Cell Line; D004249:DNA Damage; D015342:DNA Probes; D004273:DNA, Neoplasm / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D015870:Gene Expression / Q000187:drug effects*; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000302:isolation & purification; D006801:Humans; D007700:Kinetics; D011061:Poly A / Q000302:isolation & purification / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000302:isolation & purification / Q000378:metabolism; D014407:Tumor Cells, Cultured
D002087:Butyrates; D015342:DNA Probes; D004273:DNA, Neoplasm; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D020148:Butyric Acid; D011061:Poly A