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• W2151290007 abstract "Previously, we showed that mild heat shock modulates patterns of cell death in response to glucose deprivation (GD), a common characteristic of the tumor microenvironment, by switching necrosis to apoptosis through ERK-dependent suppression of reactive oxygen species production in A549 cells. In the present study, we further examined the molecular mechanism underlying mild heat shock-induced necrosis-to-apoptosis switch. We examined the possible implication of p53 and heat shock proteins (HSPs) in the mechanism. Inhibition of p53 by pifithrin-alpha or p53 siRNA markedly suppressed apoptosis induced by heat shock/GD. On the other hand, silencing of HSP27, but not of HSP70, reversed heat shock/GD-induced apoptosis to necrosis, and HSP27 overexpression suppressed GD-induced necrosis. We further demonstrate that mild heat shock activated AKT and ERK1/2 through phosphorylation. Prevention of PI3K by LY294002 blocked heat shock/GD-induced apoptosis without reversing the cell death mode to necrosis, while inhibition of MEK1/2 by U0126 reversed heat shock/GD-induced apoptosis to necrosis, indicating a different role(s) of PI3K and ERK1/2 in heat shock/GD-induced cell death mode determination. We also found that mild heat shock increased HSP27 and p53 protein levels dependent on PI3K and suppressed the GD-induced increase in RIPA-insoluble HSP27 and p53 protein levels dependent on PI3K and ERK1/2. In conclusion, these results indicate that PI3K-dependent HSP27 and p53 induction and PI3K- and ERK1/2-dependent inhibition of the GD-induced increase in RIPA-insoluble HSP27 and p53 protein levels by heat play a key role(s) in heat shock-mediated switch of GD-induced necrosis to apoptosis." @default.
• W2151290007 created "2016-06-24" @default.
• W2151290007 creator A5001282484 @default.
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• W2151290007 date "2009-12-27" @default.
• W2151290007 modified "2023-09-27" @default.
• W2151290007 title "Implication of PI3K-dependent HSP27 and p53 expression in mild heat shock-triggered switch of metabolic stress-induced necrosis to apoptosis in A549 cells" @default.
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• W2151290007 doi "https://doi.org/10.3892/ijo_00000511" @default.
• W2151290007 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20043073" @default.
• W2151290007 hasPublicationYear "2009" @default.
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