Increased resistance of the radiosensitive M10 mutant cells of the L5178Y mouse lymphoma cell line to heat-induced apoptosis.
M10 cells, which are deficient in the repair of DNA DSBs and are therefore radiosensitive, are about twofold more thermoresistant than their parental L5178Y cells. We found that, after heat shock at 43 degrees C under conditions resulting in 10% survival (D(10)), M10 cells did not undergo apoptosis, whereas L5178Y cells did undergo apoptosis. M10 cells, but not L5178Y cells, constitutively expressed Hsp72 protein. Moreover, the M10 cells accumulated higher amounts of the heat-inducible form of Hsp72. The patterns of activation of the DNA-binding activity of HSF (heat-shock factor) differed in M10 and L5178Y cells. In response to heat shock, M10 cells accumulated greater amounts of Trp53 protein (formerly known as p53) than the parental cells. Cdkn1a (formerly known as p21, Waf1) was constitutively expressed and further accumulated after heat shock only in M10 cells. We suggest that heat-inducible Hsp72 to a larger extent, and constitutive Hsp72 to a lesser extent, together with Cdkn1a may be involved in the protection of M10 cells against heat-induced apoptosis. Apoptosis in these cells is likely to occur in Trp53-dependent manner.
Ostapenko
V V
VV
Department of Radiology, Kansai Medical University, Osaka, 570-8506, Japan.
Wang
X
X
Ohnishi
K
K
Takahashi
A
A
Yamamoto
I
I
Tanaka
Y
Y
Ohnishi
T
T
D000818:Animals; D017209:Apoptosis / Q000235:genetics* / Q000528:radiation effects; D002453:Cell Cycle / Q000235:genetics; D016923:Cell Death / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000378:metabolism; D006358:Hot Temperature; D007940:Leukemia L5178 / Q000235:genetics* / Q000473:pathology* / Q000532:radiotherapy; D051379:Mice; D011836:Radiation Tolerance / Q000235:genetics*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D016159:Tumor Suppressor Protein p53