[問題] 麻煩幫忙解釋一下 paper
Paper : THE JOURNAL OF BIOLOGICAL CHEMISTRY
Vol. 279, No. 47, Issue of November 19, pp. 49420–49429, 2004
Critical Role of Endogenous Akt/IAPs and MEK1/ERK Pathways in
Counteracting Endoplasmic Reticulum Stress-induced Cell Death*
Ping Hu侩, Zhang Han, Anthony D. Couvillon, and John H. Exton
闺teracting Endoplasmic Reticulum Stress-induced Cell Death
我妹妹看這篇 paper ，有一段看不太懂意思，麻煩大家幫忙翻譯一下要義：
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To elucidate whether activation of the PI3K/Akt pathway is
required to protect cells from ER stress-induced cell death, we
first assessed the effect of the PI3K inhibitor LY294002. As
shown by phase-contrast microscopy and a cell viability assay
(MTT assay) in Fig. 2 (C and D), co-incubation with LY294002
significantly sensitized MCF-7 cells to thapsigargin- or tunicamycin-
induced cell death. LY294002 treatment alone had no
effect on cell viability. Similar results were obtained when the
same experiments were performed with H1299 cells (Fig. 2D).
To further confirm that Akt signaling is protective of cell survival
during ER stress, we established MCF-7 cell pools stably
expressing HA-tagged dominant-negative (DN) Akt in which a
point mutation (K197M) was introduced at a site required for
kinase activity. Control cells were transfected with empty vector.
Stable transfectants were identified by Western blotting
with an HA-specific monoclonal antibody. A cell viability assay
showed that ectopic expression of DN-Akt significantly increased
thapsigargin- and tunicamycin-induced cell death (Fig.
2E). Similar results were obtained in H1299 cell expressing
DN-Akt (data not shown). These results provide evidence that
activation of the PI3K/Akt pathway is a critical cell survival
response to ER stress.
Akt-dependent Activation of mTOR Is Not Required for Aktmediated
Survival Signaling in ER Stress—Recent research
has shown that mTOR, an established Akt effector, is essential
for Akt-mediated survival signaling . There is also
much evidence that mitogens and growth factors stimulate
phosphorylation of mTOR at Ser2448 . It was therefore
interesting to investigate the role of mTOR in regulation of ER
stress considering its critical controlling role in protein synthesis.
Acute phosphorylation of mTOR at Ser2448 was found in
MCF-7 cells treated with thapsigargin or tunicamycin, which
was blocked by either LY249002 or expression of DN-Akt (Fig.
3A). Next, we tested whether activated mTOR contributes to
cell survival during ER stress. As shown in Fig. 3B, co-incubation
of MCF-7 cells with rapamycin, an inhibitor of mTOR, did
not increase ER stress-induced cell death. Our data indicate
that ER stress induces phosphorylation of mTOR in an Akt-dependent
manner; however, this is not involved in cell survival.
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※ 編輯: ZeroTeacher 來自: 211.74.178.133 (11/24 20:12)
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