Reversal of TNF-alpha resistance by hyperthermia: role of mitochondria.
The aim of this study is to examine the effect of hyperthermia on tumour necrosis factor-alpha (TNF-alpha) resistance in L929-11E cells. L929-11E is a TNF-alpha resistant variant derived from L929 cells, a commonly used model for TNF-alpha study. Based on the results from flow cytometry and Western blotting, hyperthermia (43 degrees C, 3 h) was found to induce apoptosis, mitochondrial potential (delta psi(m)) depolarization and release of cytochrome c in L929-11E cells. Similar responses were found in L929 cells when treated with TNF-alpha. Heating at 43 degrees C for 1 h did not significantly damage the mitochondria of L929-11E cells but partially reversed their resistance to TNF-alpha. When L929-11E cells were sequentially treated with heating (43 degrees C, 1 h) and TNF-alpha, a more severe damage in mitochondria was observed. Taken together, our results indicate (1) hyperthermia induced apoptosis in L929-11E cells via mitochondrial damages in a way very similar to the action of TNF-alpha in L929 cells, (2) hyperthermia could be used to overcome TNF-alpha resistance by altering mitochondrial activities and (3) L929-11E and its parental cells provide a useful model in elucidating the signalling linkage between TNF-alpha receptor and mitochondria.
Ko
S
S
Department of Biochemistry, The Chinese University of Hong Kong, Shatin, China.
Yuen
W F
WF
Fung
K P
KP
Lee
C Y
CY
Choy
Y M
YM
Cheng
H K
HK
Kwok
T T
TT
Kong
S K
SK
D002460:Cell Line; D003574:Cytochrome c Group / Q000378:metabolism; D006979:Hyperthermia, Induced; D008564:Membrane Potentials; D008928:Mitochondria / Q000201:enzymology / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D003574:Cytochrome c Group; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha