Endogenous tumour necrosis factor regulates heat-inducible heat shock protein 72 synthesis.
Endogenous tumour necrosis factor (enTNF) acts as a resistant factor against cytotoxicity of heat by induction of manganous superoxide dismutase (MnSOD), thereby scavenging reactive oxygen free radicals. On the other hand, it is also well known that heat shock proteins (HSPs), which are induced by heat-stress, behave as cytoprotecting factor against this stress. However, the relationship of these two resistant factors is not yet elucidated. In the present study we would therefore propose the possibility that enTNF enhances HSP72 expression. Heat-sensitive L-M (mouse tomourigenic fibroblast) cells, which normally do not express enTNF, were transfected with a nonsecretory-type human TNF expression vector to produce enTNF. Stable transfectants showed resistance to heat treatment and an increase of HSP72 expression. Conversely, when HeLa (human uterine cervical cancer) cells, which normally produce an appreciable amount of enTNF, were transfected with an antisense TNF mRNA expression vector to inhibit enTNF synthesis, their heat sensitivity was enhanced and HSP72 expression was reduced by half. In conclusion, these findings indicate that enTNF regulates heat-inducible HSP72 synthesis.
Department of Laboratory Diagnosis, Sapporo Medical University, School of Medicine, Japan.
N
N
Watanabe
N
N
Tsuji
S
S
Akiyama
H
H
Sasaki
T
T
Okamoto
D
D
Kobayashi
T
T
Sato
T
T
Hagino
N
N
Yamauchi
Y
Y
Niitsu
D000818:Animals; D002478:Cells, Cultured; D005822:Genetic Vectors; D050884:HSP72 Heat-Shock Proteins; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D006979:Hyperthermia, Induced; D007700:Kinetics; D051379:Mice; D016372:RNA, Antisense / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology*
D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D016372:RNA, Antisense; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha