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Hyperthermia
induces translocation of apoptosis-inducing factor (AIF) and apoptosis
in human glioma cell lines
Tadateru Fukami, Satoshi Nakasu,
Kazumi Baba, Masayuki Nakajima, Masayuki Matsuda
Department of Neurosurgery,
Shiga University of Medical Science, Tsukinowa-cho, Seta, Ohtsu,
Shiga, 520-2192, Japan [T.F.*, S.N., K.B., M.M.]. Department of
Neurosurgery, Nagahama Red Cross Hospital, Nagahama, Shiga, Japan
[N.M.]. *Corresponding Author (tadateru@belle.shiga-med.ac.jp).
In the hyperthermal treatment,
the wild type (wt) p53 plays an important role in apoptosis induction
in the tumor cells.
In human gliomas, p53 frequently has some form of mutation.
The mutant type (mt) p53 does not work properly as a tumor suppressor
and this may result in poor responses during treatment.
We investigated the relationship between apoptosis-inducing factor
(AIF) and apoptosis under various thermal conditions (43, 45, and 47 °C for 1 h)
using four p53-wild or -mutant human glioma cell lines (A172, T98G,
U251MG, and YKG-1).
AIF
translocation from the mitochondria to the nucleus under hyperthermal
conditions was demonstrated by confocal laser microscopy.
The
percentage of AIF-positive nuclei increased significantly in
comparison with the control in all cell lines and in all temperature
groups except for YKG-1 at 47 °C.
Immunoblot analyses of the nuclear fraction of each
cell line revealed temperature-dependent increases in AIF.
A simultaneous release of cytochrome c from the
mitochondria to the cytosol was noted.
A flow cytometric analysis showed that apoptosis
induction occurred more often in a temperature-dependent manner in the
45 and 47 °C groups
than in the control group.
These
findings indicate that the hyperthermal conditions can lead to AIF
translocation and apoptotic cell death in the p53-mutant human glioma
cells.
The present
report is the first description of AIF-induced apoptosis in
hyperthermia.
Keywords: AIF, apoptosis, glioma cell
line, hyperthermia, p53
Copyright © 2004 Kluwer Academic Publishers.
All rights reserved
Source: http://ipsapp009.kluweronline.com/IPS/content/ext/x/J/5042/I/126/A/8/abstract.htm
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